Furanyl or thienyl pyrimidines as CDK4 inhibitors

Abstract

The present application provides compounds of Formula (I): (I) or a pharmaceutically acceptable salt thereof, that are inhibitors of cyclin-dependent kinase 4 (CDK4), as well as pharmaceutical compositions thereof, and methods of treating cancer using the same.

Description

[0001] Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0002] clinical benefit in CDK4 / 6 refractory’ patients and could address acquired resistance to standard of care. Additionally, functional inhibition of CDK4, through a CDK4 molecule, has clinical opportunity in other indications besides breast cancers. CCND1 dysregulated cancers such as sarcomas, melanoma, head & neck, etc. could potentially benefit from a CDK4 inhbitor, either as a single agent or in combination with their respective standard of care.

[0003] These data provide a rationale for considering CDK.4 as a potential target for new drug development in cancer associated with CDK4 and cyclin D expression and activity. In the last decade there has been increasing interest in the development of CDK selective inhibitors and there remains a need to discover CDK inhibitors having novel activity profiles, in particular those targeting CDK4 that spare off-target CDKs with associated toxicities, including CDK6 and CDK1 associated hematopoietic and / or gastrointestinal toxicities. This application is directed to this need and others.

[0004] SUMMARY

[0005] The present invention relates to, inter alia, compounds of Formula (I):

[0006]

[0007] or pharmaceutically acceptable salts thereof, wherein the constituent members are defined herein.

[0008] The present invention further provides pharmaceutical compositions comprising a compound described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

[0009] The present invention further provides methods of inhibiting, comprising contacting the CDK4 with a compound described herein, or a pharmaceutically acceptable salt thereof.

[0010] The present invention further provides methods of inhibiting CDK4 in a patient, comprising administering to the patient a compound described herein, or a pharmaceutically acceptable salt thereof.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0011] The present invention further provides methods of treating a disease or disorder associated with CDK.4 in a patient, comprising administering to the patient a compound described herein, or a pharmaceutically acceptable salt thereof.

[0012] The present invention further provides compounds described herein, or a pharmaceutically acceptable salt thereof, for use in any of the methods described herein.

[0013] The present invention further provides uses of a compound described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for use in any of the methods described herein.

[0014] DETAILED DESCRIPTION

[0015] The present application provides, inter alia, a compound of Formula (I):

[0016]

[0017] or a pharmaceutically acceptable salt thereof, wherein:

[0018] p is 0, 1, 2, 3, 4, 5, or 6;

[0019] each m is independently 1, 2, 3, or 4;

[0020] , Y is 0 or S, and Z is CR1; or

[0021]

[0022] . Y is CR2, and Z is O or S;

[0023] X is O, S, S(O)2, S(O)NRc, or N(-L-R4);

[0024] L is a bond, C1-6alkylene, C(O), C(O)NRa, C(O)O, S(O), S(O)2, S(O)(=NRb), or S(O)2NRa;

[0025] Ra, Rb, and Rcare each independently selected from H, C1-6alkyl, and C1-6haloalkyl;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0026] or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0027] Ring moiety A is 5-10 membered heteroaryl:

[0028] when Y is O, then R1is selected from H. D, CN. halo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl. 6-14 membered aryl. 4-15 membered heterocycloalkyl, 5-14 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-14 membered aryl-C1-4 alkyl, 4-15 membered heterocycloalkyl-C 1-4 alkyl, 5-14 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, NHORal, C(O)Rbl, C(O)NRclRdl, C(O)NRcl(ORal), C(O)ORal, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclNRclRdl. NRclC(O)Rbl, NRclC(O)ORal. NRclC(O)NRclRdl, C(=NRel)Rbl, C(=NRel)NRclRdl, NRclC(=NRel)NRclRdl, NRclC(=NRel)Rbl, NRclS(O)NRclRdl, NRclS(O)Rbl, NRclS(O)2Rbl, NRclS(O)(=NRel)Rbl, NRclS(O)2NRclRdl, S(O)Rbl, S(O)NRclRdl, S(O)2Rbl, S(O)2NRclRdl, OS(O)(=NRel)Rbl, OS(O)2Rbl, S(O)(=NRel)Rbl, SF5, P(O)RflRgl, OP(O)(ORhl)(ORn), P(O)(ORhl)(ORil), and BRjlRkl, wherein said C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl. C3-10 cycloalkyl, 6-14 membered aryl, 4-15 membered heterocycloalkyl, 5-14 membered heteroaryl, C3-10 cy cl oalkyl-C 1-4 alkyl, 6-14 membered aryl-Ci-4 alkyl, 4-15 membered heterocycloalkyl-C 1-4 alky l, and 5-14 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; or

[0029] when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci-6 haloalkyl, C2-6 alkeny l, C2-6 alkynyl, C3-10 cycloalkyl, 6-14 membered aryl, 4-15 membered heterocycloalky l, (R1A2)m-5-14 membered heteroaryl, (R1A)m-C3-10 cycloalkyl-Ci-4 alky l, (C3-10 cy cl oalkyl)-(R1A1)m-C 1-4 alkyl, 6-14 membered aryl-C 1-4 alkyl, 4-15 membered heterocycloalkyl-C 1-4 alkyl, 5-14 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, NHORal, C(O)Rbl, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclNRclRdl, NRclC(O)ORal, NRclC(O)NRclRdl, C(=NRel)Rbl, C(=NRel)NRclRdl, NRclC(=NRel)NRclRdl, NRclC(=NRel)Rbl, NRclS(O)NRclRdl, NRclS(O)Rbl, NRclS(O)2Rbl, NRclS(O)(=NRel)Rbl, NRclS(O)2NRclRdl, S(O)Rbl, S(O)NRclRdl, S(O)2Rbl. OS(O)(=NRel)Rbl. OS(O)2Rbl, S(O)(=NRel)Rbl, SF5, P(O)RflRgl, OP(O)(ORhl)(ORil), P(O)(ORhl)(ORil), and BRjlRkl, wherein said C2-6alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-14 membered aryl, 4-15 membered heterocycloalkyl, 6-14 membered aryl-C 1-4 alkyl, 4-15 membered heterocycloalkyl-C 1-4 alkyl, and 5-14 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0030] alkyl and (ii) the C1-6haloalkyl portion of (R1A1)m-C1-6haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-14 membered heteroaryl portion of said (R1A2)m-5-14 membered heteroaryl, (ii) the C3-10 cy cl oalkyl-C 1-4 alkyl portion of (R1A)m-C3-10 cycloalkyl-Ci-4 alkyl, and (iii) the C3-10 cycloalkyl-Ci-4 alkyl portion of (C3-10 cycloalkyl)-(R1A1)m-Ci-4 alkyl are each optionally substituted by 1, 2. or 3 independently selected R1A4substituents;

[0031] each Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R1Asubstituents;

[0032] or, any Rcland Rdlattached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0033] each Rb1is independently selected from C1-6 alkyl, C1-6 haloalkyl. C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0034] each Relis independently selected from H, OH, CN, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl;

[0035] each Rfland Rglis independently selected from H, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl;

[0036] each Rhland Rilis independently selected from H, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0037] heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl;

[0038] each Rjland Rklis independently selected from OH, C1-6alkoxy, and C1-6haloalkoxy; or any Rjland Rklattached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6alkyl and C1-6haloalkyl; each R1Ais independently selected from D, halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11. SRa11, NHORa11, C(O)Rb11, C(O)NRcllRd11, C(O)NRcll(ORa11), C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllNRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, C(=NRell)Rb11, C(=NRell)NRcllRdll, NRcllC(=NRell)NRcllRd11, NRcllC(=NRell)Rb11, NRcllS(O)NRcllRd11, NRcllS(O)Rb11, NRcllS(O)2Rb11, NRcllS(O)(=NRell)Rb11, NRcllS(O)2NRcllRd11, S(O)Rb11, S(O)NRcllRd11, S(O)2Rb11. S(O)2NRcllRd11.

[0039]

[0040] OS(O)(=NRell)Rb11, OS(O)2Rb11, S(O)(=NRell)Rb11, SF5, P(O)RfllRg11, OP(O)(ORhll)(ORin), P(O)(ORhll)(ORin), and BR'lkRk11, wherein said Ci-6alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0041] each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-C1-4alkoxy. (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C1-4alkyl, ORm11, SRa11, NHORa11, C(O)Rb11, C(O)NRcllRd11, C(O)NRcll(ORa11), C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllNRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, C(=NRell)Rb11, C(=NRell)NRcllRd11, NRcllC(=NRell)NRcllRd11, NRcllC(=NRell)Rb11, NRcllS(O)NRcllRd11. NRcllS(O)Rb11, NRcllS(O)2Rb11, NRcllS(O)(=NRell)Rb11, NRcllS(O)2NRcllRdll, S(O)Rb11, S(O)NRcllRd11, S(O)2Rb11, S(O)2NRcllRd11, OS(O)(=NRell)Rbll, OS(O)2Rb11, S(O)(=NRell)Rb11, SF5, P(O)RfllRg11, OP(O)(ORhll)(ORin), P(O)(ORhll)(ORin), and BRjllRk11, wherein said C2-6alkenyl, C2-6alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0042] Ci-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R1Bsubstituents;

[0043] each R1A2is independently selected from CN, NO2, (R1B)m-C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, (R1B)m-C1-4alkoxy, (R1B)m-C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl. ORm11, SRa11, NHORa11, C(O)Rb11, C(O)NRcllRd11, C(O)NRcll(ORa11), C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllNRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, C(=NRell)Rb11, C(=NRell)NRcllRd11, NRcllC(=NRell)NRcllRd11, NRcllC(=NRell)Rb11, NRcllS(O)NRcllRd11, NRcllS(O)Rb11, NRcllS(O)2Rb11, NRcllS(O)(=NRell)Rbll, NRcllS(O)2NRcllRdll, S(O)Rbll, S(O)NRcllRdll, S(O)2Rbll, S(O)2NRcllRdll, OS(O)(=NRell)Rbll, OS(O)2Rbll, S(O)(=NRell)Rbll, SF5, P(O)RfllRg11, OP(O)(ORhll)(ORill), P(O)(ORhll)(ORill), and BRjllRkll, wherein said C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyd are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0044] each R1A3is independently selected from halo, OH, C1-4alkoxy, and C3-7cycloalkyl, wherein said C1-4 alkoxy and C3-7 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0045] each R1A4is independently selected from halo, OH, Ci-6 alkyl, C1-4 alkoxy, and C3-7 cycloalkyl, wherein said C1-6 alky l, C1-4 alkoxy, and C3-7 cycloalky 1 are each optionally- substituted with 1, 2. 3, or 4 independently selected R1Bsubstituents;

[0046] each Ral1, Rcl1, and Rdl1is independently selected from H, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0047] or, any Rcl1and Rdl1attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0048] heterocycloalkyl group is optionally substituted with 1, 2. 3, or 4 independently selected R1Bsubstituents;

[0049] each Rbllis independently selected from C1-6alkyl, C1-6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0050] each Rel1is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4alkyl;

[0051] each Rfl1and Rgl1is independently selected from H, Ci-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0052] each Rhl1and Ril1is independently selected from H, C1-6alkyl, C1-6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0053] each Rjl1and Rkl1is independently selected from OH, C1-6alkoxy, and C1-6haloalkoxy;

[0054] or any Rjl1and Rkl1attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2. 3, or 4 substituents independently selected from C1-6 alkyl and C1-6 haloalkyl; each Rml1is independently selected from C1-6alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0055] each R1Bis independently selected from halo, CN, NO2, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, 5-6 membered heteroaryl-C1-4alkyl, ORa12, SRa12, NHORa12,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0056] C(O)Rb12, C(O)NRc12Rd12, C(O)NRcl2(ORa12). C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12. NRcl2Rd12, NRcl2NRcl2Rd12, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, C(=NRel2)Rb12, C(=NRel2)NRcl2Rd12, NRcl2C(=NRel2)NRcl2Rd12, NRcl2C(=NRel2)Rb12, NRcl2S(O)NRcl2Rd12, NRcl2S(O)Rb12, NRcl2S(O)2Rb12, NRcl2S(O)(=NRel2)Rb12, NRcl2S(O)2NRcl2Rd12, S(O)Rb12, S(O)NRcl2Rd12, S(O)2Rb12. S(O)2NRcl2Rd12, OS(O)(=NRel2)Rb12, OS(O)2Rb12, S(O)(=NRel2)Rb12, SF5. P(O)Rfl2Rg12,

[0057]

[0058] OP(O)(ORhl2)(ORi12), P(O)(ORhl2)(ORi12), and BRjl2Rkl2, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0059] each Ral2, Rcl2, and Rdl2is independently selected from H, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky 1, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alky l, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0060] or, any Rcl2and Rdl2attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0061] each Rbl2is independently selected from C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0062] each Rel2is independently selected from H, OH, CN, C1-6alkyl, C1-6alkoxy, C1-6haloalkyl, C1-6haloalkoxy, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0063] each Rfl2and Rgl2is independently selected from H, Ci-6 alkyl, Ci-6 alkoxy. Ci-6 haloalkyl, Ci -6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, ph enyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0064] each Rh12and Ri12is independently selected from H. Ci-s alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyd;

[0065] each Rj12and Rk12is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

[0066] or any Rj12and Rk12attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted yyith 1, 2, 3, or 4 substituents independently selected from C1-6 alk 4 and C 1-6 haloalkyl;

[0067] R2is selected from H, D. halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, C3-4 cycloalkyl-Ci-4 alkyl, ORb2, SRb2, NHORa2, C(O)Rb2, C(O)NRc2Rd2, C(O)NRc2(ORa2), C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(=NRe2)Rb2, C(=NRe2)NRc2Rd2, NRc2C(=NRe2)NRc2Rd2, NRc2C(=NRe2)Rb2, NRc2S(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)(=NRe2)Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2. and S(O)2NRc2Rd2, wherein said C1-6alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, and C3-4 cycloalkyl-C 1-4 alkyd are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0068] each Ra2, Rc2, and Rd2is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0069] each Rb2is independently selected from C1-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0070] each Re2is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;

[0071] each R3is independently selected from D, halo, CN, C1-6 alkyl, C 1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa3, SRa3, NHORa3, C(O)Rb3, C(O)NRc3Rd3,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0072] C(O)NRc3(ORa3), C(O)ORa3, OC(O)Rb3. OC(O)NRc3Rd3, NRc3Rd3, NRc3NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3C(=NRe3)Rb3, NRc3S(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)(=NRe3)Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-Ci.4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0073] each Ra3, Rc3, and Rd3is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0074] each Rb3is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0075] each Re3is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, and C1-6 haloalkoxy;

[0076] R4is selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alky l, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C1-4alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0077] each R4Ais independently selected from oxo, D, halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0078] C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl. 5-6 membered heteroaryl-C1-4 alkyl, ORa41, SRa41, NHORa41, C(O)Rb41, C(O)NRc41Rd41, C(O)NRc41(ORa41), C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41NRc41Rd41, NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, C(=NRe41)Rb41, C(=NRe41)NRc41Rd41, NRc41C(=NRe41)NRc41Rd41, NRc41C(=NRe41)Rb41, NRc41S(O)NRc41Rd41, NRc41S(O)Rb41, NRc41S(O)2Rb41. NRc41S(O)(=NRe41)Rb41. NRc41S(O)2NRc41Rd41, S(O)Rb41. S(O)NRc41Rd41, S(O)2Rb41, S(O)2NRc41Rd41, OS(O)(=NRe41)Rb41, OS(O)2Rb41, and S(O)(=NRe41)Rb41, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0079] each Ra41, Rc41, and Rd41is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0080] or, any Rc41and Rd41attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0081] each Rb41is independently selected from Ci-s alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyd, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0082] each Re41is independently selected from H, OH. CN, C1-6 alkyl. C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl;

[0083] each R4Bis independently selected from D, halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0084] cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C1-4 alkyl, ORa42, SRa42, NHORa42, C(O)Rb42, C(O)NRc42Rd42, C(O)NRc42(ORa42), C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, C(=NRe42)Rb42, C(=NRe42)NRc42Rd42, NRc42C(=NRe42)NRc42Rd42, NRc42C(=NRe42)Rb42, NRc42S(O)NRc42Rd42, NRc42S(O)Rb42, NRc42S(O)2Rb42. NRc42S(O)(=NRe42)Rb42. NRc42S(O)2NRc42Rd42, S(O)Rb42. S(O)NRc42Rd42, S(O)2Rb42, S(O)2NRc42Rd42, OS(O)(=NRe42)Rb42, OS(O)2Rb42, and S(O)(=NRe42)Rb42, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0085] each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0086] each Rb42is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2. 3, or 4 independently selected RGsubstituents;

[0087] each Re42is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl;

[0088] each R5is independently selected from D, halo, NO2, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroary l, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, ORa5, SRa5, NH0Ra5, C(O)Rb5, C(O)NRc5Rd5, C(O)NRc5(ORa5), C(O)ORa5, OC(O)Rb5,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0089] OC(O)NRc5Rd5, NRc5Rd5, NRc5NRc5Rd5. NRc5C(O)Rb5, NRc5C(O)ORa5. NRc5C(O)NRc5Rd5, C(=NRe5)Rb5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5C(=NRe5)Rb5, NRc5S(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)(=NRe5)Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, S(O)2NRc5Rd5, OS(O)(=NRe5)Rb5, OS(O)2Rb5, S(O)(=NRe5)Rb5, SF5, P(O)Rf5Rg5, OP(O)(ORh5)(ORi5), P(O)(ORh5)(ORi5), and BRj5Rk5, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alky l, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0090] each Ra5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalky 1-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3- 10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0091] or, any Rc5and Rd5attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0092] each Rb5is independently selected from C1-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl -C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, and 5-10 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0093] each Re5is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroary l, C3-10 cycloalkyl-Ci-4 alky 1, 6-10 membered aryl-C 1-4 alky l, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0094] each Rf5and Rg5is independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci- 6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alky 1, 6-10 membered aryl-Ci-4 alkyd, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;

[0095] each Rh5and Ri5is independently selected from H, Ci-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyd, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;

[0096] each Rj5and Rk5is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy; or, any Rj5and Rk5attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-6 alky l and C 1-6 haloalkyl;

[0097] each R5Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-C1-4 alkyl, 5-10 membered heteroaryl-C1-4 alkyl, ORa51, SRa51, NHORa51, C(O)Rb51, C(O)NRc51Rd51, C(O)NRc51(ORa51), C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, C(=NRe51)Rb51, C(=NRe51)NRc51Rd51, NRc51C(=NRe51)NRc51Rd51, NRc51C(=NRe51)Rb51, NRc51S(O)NRc51Rd51, NRc51S(O)Rb51, NRc51S(O)2Rb51, NRc51S(O)(=NRe51)Rb51, NRc51S(O)2NRc51Rd51, S(O)Rb51, S(O)NRc51Rd51, S(O)2Rb51, S(O)2NRc51Rd51, OS(O)(=NRe51)Rb51, OS(O)2Rb51, S(O)(=NRe51)Rb51. SF5, P(O)Rf51Rg51,

[0098]

[0099] OP(O)(ORh51)(OR‘51), P(O)(ORb51)(ORi51), and BRj51Rk51, wherein said C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyd, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered ar 4-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaiy 1-C 1-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R5Bsubstituents;

[0100] each Ra51, Rc51, and Rd51is independently selected from H, Ci-6 alkyd, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered ary l, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0101] alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyd, and 5-10 membered heteroary 1-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0102] or, any Rc51and Rd51attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0103] each Rb51is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl. 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl -C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalky 1-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0104] each Re51is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl;

[0105] each Rf51and Rg51is independently selected from H, C1-6 alkyl, C1-6 alkoxy. C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl;

[0106] each R1’51and R151is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C1-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroary 1-C 1-4 alkyl;

[0107] each Rj51and Rk51is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

[0108] or, any Rj51and Rk51attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2. 3, or 4 substituents independently selected from C1-6 alkyl and C 1-6 haloalkyl;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0109] each R5Bis independently selected from D, halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa52, SRa52, NHORa52, C(O)Rb52, C(O)NRc52Rd52, C(O)NRc52(ORa52). C(O)ORa52, OC(O)Rb52, OC(O)NRc52Rd52, NRc52Rd52, NRc52NRc52Rd52, NRc52C(O)Rb52, NRc52C(O)ORa52, NRc52C(O)NRc52Rd52. C(=NRe52)Rb52, C(=NRe52)NRc52Rd52, NRc52C(=NRe52)NRc52Rd52, NRc52C(=NRe52)Rb52, NRc52S(O)NRc52Rd52, NRc52S(O)Rb52, NRc52S(O)2Rb52, NRc52S(O)(=NRe52)Rb52, NRc52S(O)2NRc52Rd52, S(O)Rb52, S(O)NRc52Rd52, S(O)2Rb52, S(O)2NRc52Rd52,

[0110]

[0111] OS(O)(=NRe52)Rb52, OS(O)2Rb52, S(O)(=NRe52)Rb52, SF5, P(O)Rf52Rg52, OP(O)(ORh52)(ORi52), P(O)(ORh52)(ORi52), and BR'52Rk52. wherein said C1-6alkyl, C2-6 alkenyl, C2-6 alkynyL C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alky l, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0112] each Ra52, Rc52, and Rd52is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0113] or, any Rc52and Rd52attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0114] each Rb52is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0115] each Re52is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0116] heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky l-C 1-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0117] each Rf52and Rg52is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0118] each Rh52and Ri52is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;

[0119] each Rj52and Rk52is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;

[0120] or, any Rj52and Rk52attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2. 3, or 4 substituents independently selected from C1-6 alkyl and C 1-6 haloalkyl; and each RGis independently selected from OH, NO2, CN, halo, C1-3 alkyd, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyd, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci-3 alkylthio, C1-3 alkylsulfinyl, C1.3 alkylsulfonyl, carbamyl, C1.3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxy carbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alkydsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyd)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C 1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-3 alkydaminocarbonylamino, and di(Ci-3 alkyd)aminocarbonylamino.

[0121] In some embodiments, n is 0, 1, or 2.

[0122] In some embodiments, n is 0 or 1.

[0123] In some embodiments, n is 1.

[0124] In some embodiments, p is 0, 1, 2, 3. 4, or 5.

[0125] In some embodiments, p is 0, 1, 2, 3, or 4.

[0126] In some embodiments, p is 0, 1, 2, or 3.

[0127] In some embodiments, p is 0.

[0128] In some embodiments, p is 1.

[0129] In some embodiments, p is 2.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0130] In some embodiments, p is 3.

[0131] In some embodiments, each m is independently 1 or 2.

[0132] In some embodiments, X is O, S(O)2, S(O)NRC, orN(-L-R4).

[0133] In some embodiments, X is O, S(O)2, or N(-L-R4).

[0134] In some embodiments, X is O or N(-L-R4).

[0135] In some embodiments, X is O.

[0136] In some embodiments, X is S.

[0137] In some embodiments, X is S(O)2.

[0138] In some embodiments, X is S(O)NRC.

[0139] In some embodiments, X is N(-L-R4).

[0140] In some embodiments, L is C(O), C(O)NRa, C(O)O, S(O), S(O)2, or S(O)2NRa.

[0141] In some embodiments, L is C(O), C(O)O, S(O)2, or S(O)2NRa.

[0142] In some embodiments, L is a bond.

[0143] In some embodiments, L is C1-6 alkylene.

[0144] In some embodiments, L is C(O).

[0145] In some embodiments, L is C(O)NRa.

[0146] In some embodiments, L is C(O)O.

[0147] In some embodiments, L is S(O).

[0148] In some embodiments, L is S(O)2.

[0149] In some embodiments, L is S(O)(=NRb).

[0150] In some embodiments, L is S(O)2NRa.

[0151] In some embodiments, Ra, Rb, and Rcare each independently selected from H and C1-3 alkyl.

[0152] In some embodiments, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

[0153] In some embodiments, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

[0154] In some embodiments, Ring moiety A is 5-9 membered heteroaryl.

[0155] In some embodiments, Ring moiety A is 5-6 membered heteroaryl.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0156] In some embodiments, Ring moiety A is a pyrazole ring, a thiazole ring, an isothiazole ring, an oxazole ring, an isoxazole ring, an oxadiazole ring, a thiodiazoloring, a pyridine ring, a pyridazine ring, a pyrazine ring, a pyrimidine ring, an indazole ring, an indole ring, a pyrazolopyridine ring, a pyrrolopyridine ring, a pyrazolopyrimidine ring, or a pyrrolopyrmidine ring.

[0157] In some embodiments. Ring moiety A is a pyrazole ring, a thiazole ring, a pyridine ring, a pyridazine ring, or an indazole ring.

[0158] In some embodiments, Ring moiety A is a pyrazole ring, a thiazole ring, an isothiazole ring, a pyridine ring, a pyridazine ring, or an indazole ring.

[0159] In some embodiments, when Y is O, then R1is selected from H, D, CN, halo. Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alky l, 4-10 membered heterocycloalkyl-C 1-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, ORhl, SRbl, C(O)Rbl, C(O)NRclRdl. C(O)ORal, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)Rbl. NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl, S(O)2Rbl, and S(O)2NRclRdl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaiyl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aiyl-C1-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0160] In some embodiments, when Y is O, then R1is selected from H, D, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, C(O)Rhl, C(O)NRclRdl, C(O)ORal, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)Rbl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl, S(O)2Rbl, and S(O)2NRclRdl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0161] In some embodiments, when Y is O, then R1is selected from H, D, CN, halo. C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0162] heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1.4 alkyl, ORbl, SRbl, and NRclRdl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R1Asubstituents.

[0163] In some embodiments, when Y is O, then R1is selected from H, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and ORbl; wherein said C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0164] In some embodiments, when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, (R1A2)m-5-10 membered heteroaryl, (R1A)m-C3-10 cycloalkyl-C 1-4 alkyl, (C3-10 cycloalkyl)-(R1A1)m-C 1-4 alkyl, 6-10 membered aryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, C(O)Rb1, OC(O)Rb1, OC(O)NRc1Rdl, NRclRdl, NRclC(O)ORal, NRclC(O)NRclRdl,

[0165] NRclS(O)2Rbl, NRclS(O)2NRclRdl, and S(O)2Rbl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 6-10 membered aryl-Ci-4 alky l, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-Ci-6 haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-10 membered heteroaryl portion of said (R1A2)m-5-10 membered heteroaryl, (ii) the C3-10 cycloalkyl-C 1-4 alkyl portion of (R1A)m-C3-10 cycloalkyl-C 1-4 alkyl, and (iii) the C3-io-cycloalkyl-Ci-4 alkyl portion of (C3-10 cycloalkyl)-(R1A1)m-Ci-4 alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents.

[0166] In some embodiments, when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-C1-6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl. (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl, (C3-7 cy cl oalkyl)-(R1A1)m-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, C(O)Rbl, OC(O)Rbl, OC(O)NRclRdl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0167] NRclRdl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl. and S(O)2Rbl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1.4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-C1-6haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, (ii) the C3-7 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl, and (iii) the C3-7 cycloalkyl-C1-4 alkyl portion of (C3-7 cycloalkyl)-(R1A1)m-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents.

[0168] In some embodiments, when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl. (R1A)m-C3-7cycloalkyl-Ci-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, and NRclRdl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-Ci-6 haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, and (ii) the C3-7 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl are each optionally- substituted by 1, 2, or 3 independently selected R1A4substituents.

[0169] In some embodiments, when Y is S, then R1is selected from H, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl. 4-7 membered heterocycloalkyl-Ci-4 alkyl, and ORbl, wherein said C2-6 alkynyl, 4-7 membered heterocycloalkyl, phenyl, and 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; and wherein the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl is optionally substituted by 1, 2, or 3 independently selected R1A4substituents.

[0170] In some embodiments:Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0171] each Ral, Rcl. and Rdlis independently selected from H. Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl -C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0172] each Rblis independently selected from Ci-6 alky 1, Ci-6 haloalky l, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl -Ci -4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alky 1, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0173] each R1Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1.4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11. OC(O)NRc11Rd11, NRc11Rd11, NRcl1C(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11. and S(O)2NRcllRd11, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0174] each Ral1, Rcl1, and Rdl1is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalk l. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0175] each Rbl1is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0176] each R1Bis independently selected from halo, CN, NO2, C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRcl2Rd12, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRcl2Rd12, wherein said C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0177] each Ral2, Rcl2, and Rdl2is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl, wherein said Ci-6 alky l and C1-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0178] each Rbl2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0179] when present, each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy, (R, B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl. 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1.4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcl1Rd11, NRcllRd11, NRcllC(O)Rbn, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rbn, NRcllS(O)2NRcllRdn, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0180] when present, each R1A2is independently selected from CN, NO2, (R1B)m-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11. NRcllS(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0181] Ci-6 haloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0182] when present, each R1A3is independently selected from halo, OH. and C1-4 alkoxy, wherein said C1-4 alkoxy is optionally substituted with 1, 2, 3. or 4 independently selected R1Dsubstituents; and

[0183] when present, each R1A4is independently selected from halo, OH, C1-6 alkyl, and C1-4 alkoxy, wherein said C1-6 alkyl and C1-4 alkoxy are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents; and

[0184] when present, each Rml1is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents.

[0185] In some embodiments:

[0186] each Ral, Rcl, and Rdlis independently selected from H, C1-6 alky l, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0187] each Rblis independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0188] each R1Ais independently selected from halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0189] C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11. OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;

[0190] each Ral1, Rcl1, and Rdl1is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0191] each Rbl1is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0192] each R1Bis independently selected from halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRcl2Rd12, NRcl2C(O)Rb12. NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12. S(O)2Rb12, and S(O)2NRcl2Rd12;

[0193] each Ral2, Rcl2, and Rdl2is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0194] each Rbl2is independently selected from Ci-6 alkyl and Ci-6 haloalky l;

[0195] when present, each R1A1is independently selected from CN, C2-6 alkenyl. C2-6 alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11. NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NR‘;11Rd11,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0196] wherein said C2-6 alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0197] when present, each R1A2is independently selected from CN, NO2. (R1B)m-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORm11, SR’11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRdll, NRcllS(O)2Rb11, NRcllS(O)2NRcllRdll, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0198] when present, each R1A3is independently selected from halo, OH, and C1.4 alkoxy; when present, each R1A4is independently selected from halo, OH, C1-6 alkyl, and C1-4 alkoxy; and

[0199] when present, each Rml1is independently selected from C2-6alkenyl, C2-6alkynyl, C3-5cycloalkyl, and 4-5 membered heterocycloalkyl.

[0200] In some embodiments, R2is selected from H, D, halo, CN, Ci-6 alkyd, C1-6 haloalkyl, C3-4 cycloalkyl, C3-4 cycloalkyl-Ci-4 alkyl, ORb2, SRb2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)2Rb2. NRc2S(O)2NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said C1-6alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, and C3-4 cycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0201] In some embodiments, R2is selected from H, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalky l are each optionally substituted with 1, 2. 3, or 4 independently selected RGsubstituents.

[0202] In some embodiments, R2is selected from H, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl. In some embodiments, R2is H.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0203] In some embodiments, each Ra2, Rc2, and Rd2is independently selected from H. Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl; and each Rb2is independently selected from Ci-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl.

[0204] In some embodiments, each Ra2, Rc2, and Rd2is independently selected from H, C1-6 alkyl, and Ci-6 haloalkyl; and each Rb2is independently selected from C1-6 alkyl and C1-6 haloalkyl.

[0205] In some embodiments, each R3is independently selected from D, halo, CN, Ci-6 alkyl, C 1-6 haloalkyl, C3-4 cycloalkyl, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)NRc3(ORa3), C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3. NRc3S(O)2Rb3. NRc3S(O)2NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3, wherein said Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0206] In some embodiments, each R3is independently selected from halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa3, and NRc3Rd3, wherein said Ci-6 alkyl and Ci-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents.

[0207] In some embodiments, each R3is independently selected from halo, CN, Ci-6 alkyl, C 1-6 haloalky l, ORa3, and NRc3Rd3, wherein said Ci-6 alkyd and Ci-6 haloalky l, and C3-4 cycloalky l are each optionally substituted with 1 RGsubstituent.

[0208] In some embodiments, each R3is independently selected from Ci-6 alkyl, Ci-6 alkylene-ORa3, Ci-6 alkylene-NRc3Rd3, ORa3, and NRc3Rd3.

[0209] In some embodiments, each R3is independently selected from Ci-6 alkylene-ORa3, Ci-6 alkylene-NRc3Rd3, ORa3, and NRc3Rd3.

[0210] In some embodiments, each R3is independently selected from Ci-6 alkyl, Ci-6 alkylene-OH and OH.

[0211] In some embodiments, each R3is independently selected from Ci-6 alkylene-OH and OH.

[0212] In some embodiments, each Ra3, Rc3, and Rd3is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl. wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents; and each Rb3is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0213] In some embodiments, each Ra3, Rc3, and Rd3is independently selected from H. Ci-6 alkyl, and Ci-6 haloalkyl; and each Rb3is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0214] In some embodiments, each Ra3, Rc3, and Rd3is independently selected from H and CH3; and each Rb3is CH3.

[0215] In some embodiments, R4is selected from H, Ci-6 alkyl. Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alky l, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

[0216] In some embodiments, R4is selected fromH, Ci-6 alkyd. Ci-6 haloalkyl, C3-7 cycloalky l, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, and C3-7 cy cl oalkyl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroary l, and C3-10 cycloalkyl-C 1-4 alky 1 are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

[0217] In some embodiments, R4is selected from H, Ci-6 alky l. Ci-6 haloalkyl, C3-7 cycloalky l, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein said Ci-6 alky l, Ci-6 haloalkyl, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroary l are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

[0218] In some embodiments:

[0219] each R4Ais independently selected from oxo, D, halo, CN, Ci-6 alky l, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa41, SRa41. C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0220] membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroai l-C'i-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0221] each Ra41, Rc41, and Rd41is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0222] each Rb41is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0223] each R4Bis independently selected from D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C1-4 alkyl, ORa42, SRa42, C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;

[0224] each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; and

[0225] each Rb42is independently selected from C1-6 alkyl and C1-6 haloalkyl.

[0226] In some embodiments:

[0227] each R4Ais independently selected from D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C1-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0228] membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroai l-C'i-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0229] each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalky l. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0230] each Rb41is independently selected from Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2. 3, or 4 independently selected R4Bsubstituents;

[0231] each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci.4 alkyl, ORa42, SRa42. C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;

[0232] each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alky l, and Ci-6 haloalkyl; and

[0233] each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0234] In some embodiments:

[0235] each R4Ais independently selected from oxo, D, halo, CN, Ci-6 alky l, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaiyl-Ci-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0236] membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaiyl-C i -4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0237] each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalky l. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0238] each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2. 3, or 4 independently selected R4Bsubstituents;

[0239] each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl, ORa42, SRa42, C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42. NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;

[0240] each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

[0241] each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0242] In some embodiments:

[0243] each R4Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaiyl-C 1-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41. NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalky l-C 1-4 alkyl, phenyl-C 1-4 alky l, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaiyl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0244] each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0245] each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0246] each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl, ORa42. SRa42, C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42, OC(O)Rb42.

[0247] OC(O)NRc42Rd42, NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;

[0248] each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; and

[0249] each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0250] In some embodiments:

[0251] each R4Ais independently selected from oxo, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa41, and NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R4Bsubstituents;

[0252] each Ra41, Rc41, and Rd41is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0253] each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1 or 2 independently selected R4Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0254] each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. ORa42and NRc42Rd42;

[0255] each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; and

[0256] each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

[0257] In some embodiments:

[0258] each R4Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalky I-C1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa41, and NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky I-C1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroary l-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0259] each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0260] each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1 or 2 independently selected R4Bsubstituents;

[0261] each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. ORa42and NRc42Rd42;

[0262] each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; and

[0263] each Rb42is independently selected from C1-6 alkyl and C1-6 haloalkyl.

[0264] In some embodiments, each R4Ais independently selected from oxo, halo, CN, Ci-6 alkyl, Ci-6 haloalky l, and C3-4 cycloalkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalky l are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents; each R4Bis independently selected from D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, ORa42and NRc42Rd42; and each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

[0265] In some embodiments, each R4Ais independently selected from halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl, wherein said Ci-6 alkyl, Ci-6 haloalky l, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents; each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa42andAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0266] NRc42Rd42; and each Ra42, Rc42. and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl.

[0267] In some embodiments, each R4Ais independently selected from oxo, halo, CN, C1-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl.

[0268] In some embodiments, each R4Ais independently selected from halo, CN, C1-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl.

[0269] In some embodiments, each R4Ais independently selected from oxo, halo, CN, C1-6 alkyl, and C1-6 haloalkyl.

[0270] In some embodiments, each R4Ais independently selected from halo, CN. Ci-6 alkyl, and Ci-6 haloalkyl.

[0271] In some embodiments, each R5is independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryd, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl. ORa5, SRa5, C(O)Rb5. C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5. NRc5Rd5. NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5, wherein said Ci-6 alkyd, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalky l, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents.

[0272] In some embodiments, each R5is independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa5, and NRc5Rd5, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents.

[0273] In some embodiments, each R5is independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, ORa5, and NRc5Rd5, wherein said C1-6 alkyl, C2-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0274] alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, and 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R3Asubstituents.

[0275] In some embodiments, each R5is independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa5, and NRc5Rd5, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents.

[0276] In some embodiments, each R5is independently selected from D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, ORa5, and NRc5Rd5, wherein said C1-6 alkyl, Ci-6 haloalkyl. C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents.

[0277] In some embodiments, each R5is independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, and ORa5. wherein said C 1-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents.

[0278] In some embodiments:

[0279] each Ra5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0280] each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0281] each R5Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, ORa51, SRa51, C(O)Rb51,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0282] C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)2NRc51Rd51, S(O)2Rb51, and S(O)2NRc51Rd51, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0283] each Ra31, Rc31, and Rd31is independently selected from H, Ci-6 alkyd, C1-6 haloalky l, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0284] each Rb31is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R3Bsubstituents;

[0285] each R5Bis independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa52, SRa52, C(O)Rb52, C(O)NRc52Rd52, C(O)ORa52, OC(O)Rb52, OC(O)NRc52Rd52, NRc52Rd52, NRc52C(O)Rb52, NRc52C(O)ORa52, NRc52C(O)NRc52Rd52, NRc52S(O)2Rb52, NRc52S(O)2NRc52Rd52, S(O)2Rb52, and S(O)2NRc52Rd52;

[0286] each Ra32, Rc32, and Rd32is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and

[0287] each Rb32is independently selected from Ci-6 alkyl and Ci-6 haloalky l.

[0288] In some embodiments:

[0289] each Ra5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0290] membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0291] each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0292] each R5Ais independently selected from D, halo, CN, C1-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)2NRc51Rd51, S(O)2Rb51. and S(O)2NRc51Rd51, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0293] each Ra51, Rc51, and Rd51is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, and C3-7 cycloalkyl; and

[0294] each Rb51is independently selected from C1-6 alkyl and C1-6 haloalkyl.

[0295] In some embodiments:

[0296] each Ra5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alky l, 4-7 membered heterocycloalkyl-C 1-4 alky l, and 5-6 membered heteroaryl-C1-4alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0297] each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0298] C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0299] each R5Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)2NRc51Rd51, S(O)2Rb51, and S(O)2NRc51Rd51, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0300] each Ra51, Rc51, and Rd51is independently selected from H, C1-6 alky l, and C1-6 haloalkyl;

[0301] each Rb51is independently selected from C1-6 alkyl and C1-6 haloalkyl.

[0302] In some embodiments:

[0303] each Ra5, Rc5. and Rd5is independently selected from H. C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alky l, and 5-6 membered heteroaryl-C 1-4 alky l, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0304] each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0305] each R5Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0306] membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)2NRc51Rd51, S(O)2Rb51, and S(O)2NRc51Rd51, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1.4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0307] each Ra51, Rc51. and Rd51is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, and C3-7 cycloalkyl; and

[0308] each Rb51is independently selected from C1-6 alkyl and C1-6 haloalkyl.

[0309] In some embodiments:

[0310] each Ra5, Rc5. and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alky nyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-Ci.4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyd, wherein said C1-6 alk d, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0311] each Rb5is independently selected from Ci-6 alky 1, Ci-6 haloalky l, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyd, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0312] each R5Ais independently selected from D, halo, CN, Ci-6 alky l, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51S(O)2Rb51, and NRc51S(O)2NRc51Rd51;

[0313] each Ra51, Rc51, and Rd51is independently selected from H, Ci-6 alky l, and Ci-6 haloalkyl; andAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0314] each Rb51is independently selected from C1-6 alkyl and C1-6 haloalkyl. In some embodiments:

[0315] n is 1;

[0316] p is 0, 1, 2, or 3;

[0317] each m is independently 1 or 2;

[0318] Y is O or S, and Z is CR1; or

[0319]

[0320] , Y is CR2, and Z is O or S;

[0321] X is O, S, S(O)2, S(O)NRc, or N(-L-R4);

[0322] L is C(O), C(O)NRa, C(O)O, S(O), S(O)2, or S(O)2NRa;

[0323] Raand Rcare each independently selected from H and C1-3 alkyl;

[0324] or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0325] Ring moiety A is 5-9 membered heteroaryl;

[0326] when Y is O, then R1is selected from H, D, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, C(O)Rbl, C(O)NRclRdl, C(O)ORal, OC(O)Rbl, OC(O)NRclRdl. NRclRdl. NRclC(O)Rbl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl, S(O)2Rbl, and S(O)2NRclRdl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1.4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0327] when Y is S, then R1is selected fromH, D, halo, (R1A1)m-Ci-6 alkyd, (R1A1)m-Ci.6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0328] (R1A2)m-5-6 membered heteroaryl, (R1A)m-C3-7cycloalkyl-Ci-4 alkyl, (C3-7 cycloalkyl)-(R1A1)m-C1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, C(O)Rbl, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl, and S(O)2Rbl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci.4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-Ci-6 haloalkyl are each optionally substituted by 1, 2. or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, (ii) the C3-7 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl, and (iii) the C3-7 cycloalkyl-C1-4 alkyl portion of (C3-7 cycloalky l)-(R1A1)m-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents;

[0329] each Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2.6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alky l, 4-7 membered heterocycloalkyl-Ci-4 alky l, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0330] each Rb1is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0331] each R1Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky l-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11. OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRellRd11, S(O)2Rb11,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0332] and S(O)2NRcllRd11, wherein said Ci-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0333] each Ra11, Rc11, and Rd11is independently selected from H, C1-6 alkyl. C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0334] each Rbl1is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci.4 alkyl, 4-7 membered heterocycloalky I-C1.4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0335] each R1Bis independently selected from halo, CN. NO2. Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRcl2Rd12, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRcl2Rd12, wherein said Ci-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, Ci-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0336] each Ral2, Rcl2, and Rdl2is independently selected from H, Ci-6 alkyd, and Ci-6 haloalkyl, wherein said Ci-6 alky l and Ci-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0337] each Rbl2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0338] each R1A1is independently selected from CN, C2-6 alkenyl, C2-6 alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0339] OC(O)NRcllRd11, NRcllRd11. NRcllC(O)Rb11, NRcllC(O)ORa11. NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6alkenyl, C2-6alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0340] each R1A2is independently selected from CN, NO2, (R1B)m-Ci-6 alkyl, C2.6 alkenyl, C2.

[0341] 6 alkynyl, Ci-6 haloalkyl, (R1B)m-C 1-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alky l, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl. ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)ORa11, NRc11C(O)NRc11Rd11, NRc11S(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRc11Rd11, wherein said C2-6alkenyl, C2-6alkynyl, C1-6 haloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0342] each R1A3is independently selected from halo, OH, and C1-4 alkoxy, wherein said C1-4 alkoxy is optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents; and each R1A4is independently selected from halo, OH, Ci-6 alkyl, and CM alkoxy, wherein said C1-6 alkyl and C 1-4 alkoxy are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0343] each Rm11is independently selected from C2-6 alkenyl. C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyd, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0344] R2is selected from H, D. halo. CN, Ci-6 alkyl. C1-6 haloalkyl, C3-4 cycloalkyl, C3-4 cycloalkyl-Ci-4 alkyl, ORb2, SRb2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said C1-6alkyl, C1-6haloalkyl, C3-4 cycloalkyl, and C3-4 cycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0345] each Ra2, Rc2. and Rd2is independently selected from H. Ci-6 alkyl, and Ci-6 haloalkyl; each Rb2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0346] each R3is independently selected from halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa3, and NRc3Rd3, wherein said Ci-6 alkyl and Ci-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents;

[0347] each Ra3, Rc3. and Rd3is independently selected from H. C1-6 alkyl, and C1-6 haloalkyl; R4is selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, ph enyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0348] each R4Ais independently selected from oxo, D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41. S(O)2Rb41, and S(O)2NRc41Rd41, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0349] each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alky l, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0350] each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0351] phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0352] each R4Bis independently selected from D, halo, CN, Ci-6 alkyd, Ci-6 haloalky 1, and C3-4 cycloalkyl. ORa42, SRa42, C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42. NRc42C(O)Rb42, NRc42C(O)ORa42. NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;

[0353] each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alky l, and C1-6 haloalkyl;

[0354] each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0355] each R5is independently selected from D, halo, CN, Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5. NRc5Rd5. NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5, wherein said Ci-6 alkyd, C2-6 alkenyl, C2-6 alky nyl, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky 4. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0356] each Ra5, Rc5, and Rd5is independently selected from H, Ci-6 alky l, Ci-6 haloalky l, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-7 cycloalkyl, pheny l, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0357] each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alky nyl, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0358] 6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0359] each R5Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, ORa51, SRa51, C(O)Rb51. C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)2NRc51Rd51, S(O)2Rb51, and S(O)2NRc51Rd51, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0360] each Ra51, Rc51, and Rd51is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0361] each Rb51is independently selected from C1-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0362] each R5Bis independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, C3-4 cycloalkyl, ORa52. SRa52, C(O)Rb52. C(O)NRc52Rd52, C(O)ORa52, OC(O)Rb52, OC(O)NRc52Rd52, NRc52Rd52, NRc52C(O)Rb52, NRc52C(O)ORa52, NRc52C(O)NRc52Rd52, NRc52S(O)2Rb52, NRc52S(O)2NRc52Rd52, S(O)2Rb52, and S(O)2NRc52Rd52;

[0363] each Ra52, Rc52, and Rd52is independently selected from H, Ci-6 alky l, and C1-6 haloalkyl;

[0364] each Rb52is independently selected from Ci-6 alkyl and Ci-6 haloalkyl; andAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0365] each RGis independently selected from OH, NO2, CN, halo. C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy. C1-3 alkylcarbonyl. C1-3 alkoxy carbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino. C1-3 alkoxy carbonylamino. C1-3 alkylaminocarbonyloxy. C1-3 alkylsulfonylamino, aminosulfonyl, C 1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di (C 1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

[0366] In some embodiments:

[0367] n is 1;

[0368] p is 0, 1, 2, or 3;

[0369] each m is independently 1 or 2;

[0370] Y is O or S, and Z is CR1; or

[0371]

[0372] , Y is CR2, and Z is O or S;

[0373] X is O, S, S(O)2, S(O)NRc, or N(-L-R4);

[0374] L is C(O), C(O)O, S(O)2, or S(O)2NRa;

[0375] Raand Rcare each independently selected from H and C1-3 alkyl;

[0376] Ring moiety A is 5-9 membered heteroaryl;

[0377] when Y is O, then R1is selected from H, D, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, C(O)Rbl, C(O)NRclRdl, C(O)ORal, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)Rbl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl, S(O)2Rbl, and S(O)2NRclRdl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0378] cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1.4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0379] when Y is S, then R1is selected fromH, D, halo, (R1A1)m-Ci-6 alkyd, (R1A1)m-Ci.6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl. (R1A)m-C3-7 cycloalky 1-C 1-4 alkyl, (C3-7 cycloalkyl)-(R1A1)m-C1-4 alkyl, phenyl-Ci-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C1-4alkyl, ORbl, SRbl, C(O)Rbl, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl, and S(O)2Rbl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alky l portion of said (R1A1)m-Ci-6 alkyl and (ii) the Ci-6 haloalkyl portion of (R1A1)m-C1-6haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, (ii) the C3-7 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-C1-4alkyl, and (iii) the C3-7 cycloalkyl-C1-4 alkyl portion of (C3-7 cycloalkyl)-(R1A1)m-C1-4alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents;

[0380] each Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky I-C1-4 alkyl, phenyl-C 1-4 alky l, 4-7 membered heterocycloalky 1-C 1-4 alky l, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0381] each Rb1is independently selected from C1-6 alkyl, C1-6 haloalkyl. C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0382] each R1Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11. OC(O)NRcllRd11, NRcllRd11, NRc11C(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rh11, NRcllS(O)2NRcllRd11, S(O)2Rb11. and S(O)2NRcllRd11, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;

[0383] each Ral1, Rcl1, and Rdl1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0384] each Rbl1is independently selected from Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0385] each R1Bis independently selected from halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRc12Rd12, NRc12C(O)Rb12, NRc12C(O)ORa12, NRc12C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12. S(O)2Rb12, and S(O)2NRcl2Rd12, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0386] each Ral2, Rcl2, and Rdl2is independently selected from H, Ci-6 alky l, and C1-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1. 2, 3, or 4 independently selected RGsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0387] each Rbl2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0388] each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl. ORm11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11.

[0389] OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, pheny l, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0390] each R1A2is independently selected from CN, NO2, (R1B)m-Ci-6 alkyl, C2-6 alkeny l, C2-6 alkynyl, C1-6 haloalkyl, (R1B)m-C 1-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C1-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)ORa11, NRc11C(O)NRc11Rd11, NRc11S(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0391] each R1A3is independently selected from halo, OH, and C1-4 alkoxy, wherein said C1-4 alkoxy is optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents; and each R1A4is independently selected from halo, OH, C 1-6 alkyl, and C1-4 alkoxy, wherein said C1-6 alkyl and C1-4 alkoxy are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0392] each Rml1is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alky l, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaiyl-C1-4 alkyl, which are each optionally substituted with 1, 2. 3, or 4 independently selected R1Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0393] R2is selected from H, D. halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-4 cycloalkyl, C3-4 cycloalkyl-Ci-4 alkyl, ORb2, SRb2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said C1-6alkyl, C1-6haloalkyl, C3-4 cycloalkyl, and C3-4 cycloalkyl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0394] each Ra2, Rc2, and Rd2is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; each Rb2is independently selected from C1-6 alkyl and C1-6 haloalkyl;

[0395] each R3is independently selected from halo, CN, Ci-6 alkyl, C 1-6 haloalkyl, ORa3, and NRc3Rd3, wherein said Ci-6 alkyl and Ci-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents;

[0396] each Ra3, Rc3, and Rd3is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; R4is selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroary I-C1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0397] each R4Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalk l, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryd, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroary 1-C 1-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41. NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0398] each Ra41, Rc41, and Rd41is independently selected from H, C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0399] phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0400] each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0401] each R4Bis independently selected from D, halo, CN, C1-6 alkyl, Ci-6 haloalkyl. and C3-4 cycloalkyl, ORa42, SRa42, C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;

[0402] each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0403] each Rb42is independently selected from C1-6 alkyl and C1-6 haloalkyl;

[0404] each R5is independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5, wherein said C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0405] each Ra5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0406] heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0407] each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0408] each R5Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)2NRc51Rd51, S(O)2Rb51, and S(O)2NRc51Rd51, wherein said C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0409] each Ra51, Rc51. and Rd51is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky 1, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0410] each Rb51is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;

[0411] each R5Bis independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa52, SRa52, C(O)Rb52, C(O)NRc52Rd52, C(O)ORa52,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0412] OC(O)Rb52, OC(O)NRc52Rd52, NRc52Rd52, NRc52C(O)Rb52. NRc52C(O)ORa52, NRc52C(O)NRc52Rd52, NRc52S(O)2Rb52, NRc52S(O)2NRc52Rd52, S(O)2Rb52, and S(O)2NRc52Rd52;

[0413] each Ra52, Rc52, and Rd52is independently selected from H, C1-6 alkyd, and C1-6 haloalkyl;

[0414] each Rb52is independently selected from C1-6 alkyl and C1-6 haloalkyl; and each RGis independently selected from OH, NO2, CN, halo, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(C1-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(C1-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(C1-3 alkyl)aminocarbonylamino.

[0415] In some embodiments:

[0416] n is 1;

[0417] p is 0, 1, 2, or 3;

[0418] each m is independently 1 or 2;

[0419] Y is O or S, and Z is CR1; or

[0420]

[0421] , Y is CR2, and Z is O or S;

[0422] X is O, S(O)2, or N(-L-R4);

[0423] L is C(O), C(O)NRa, C(O)O, S(O), S(O)2, or S(O)2NRa;

[0424] Rais selected from H and C1-3 alkyl;

[0425] or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring optionally substituted by 1, 2, or 3 independently selected R4Asubstituents;

[0426] Ring moiety A is 5-9 membered heteroaryl;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0427] when Y is O, then R1is selected from H, D, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORb1, SRb1, and NRc1Rd1; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0428] when Y is S, then R1is selected from H, D, halo, (R1A1)m-C1-6 alkyl, (R1A1)m-C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl, (R1A)m-C3-7 cycloalkyl-C1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORb1, SRb1, and NRc1Rd1, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-C1-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-C1-6 haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, and (ii) the C3-7 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-C1-4 alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents;

[0429] each Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0430] each Rb1is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0431] 6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0432] each R1Ais independently selected from halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa11. SRa11, C(O)Rb11. C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0433] each Ra11, Rc11, and Rd11is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0434] each Rbl1is independently selected from C1-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0435] each R1Bis independently selected from halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRcl2Rd12, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRcl2Rd12;

[0436] each Ral2, Rcl2, and Rdl2is independently selected from H, Ci-6 alky l, and C1-6 haloalkyl;

[0437] each Rbl2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0438] each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C1-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRc11C(O)Rb11, NRcllC(O)ORa11, NRc11C(O)NRc11Rd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11. wherein said C2-6 alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alky l are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0439] each R1A2is independently selected from CN, NO2, (R1B)m-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, (R1B)m-C 1-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl. ORm11. SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11. NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0440] each R1A3is independently selected from halo, OH, and C1-4 alkoxy; and

[0441] each R1A4is independently selected from halo, OH, C1-6 alkyl, and C1-4 alkoxy; each Rm11is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl;

[0442] R2is selected from H, halo, CN, C1-6 alkyl, and C1-6 haloalkyl, wherein said CM alkyl and CM haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0443] each R3is independently selected from C1-6 alkyl, C1-6 alkylene-ORa3, C1-6 alkylene-NRc3Rd3, ORa3, and NRc3Rd3;

[0444] each Ra3, Rc3, and Rd3is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; R4is selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C3-10 cycloalkyl-Ci-4 alkyl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0445] wherein said Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C3-iocycloalkyl-Ci-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0446] each R4Ais independently selected from oxo, D, halo, CN, Ci-6 alky l, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci.4 alkyl, ORa41, and NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R4Bsubstituents;

[0447] each Ra41, Rc41, and Rd41is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0448] each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1 or 2 independently selected R4Bsubstituents;

[0449] each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa42and NRc42Rd42;

[0450] each Ra42, Rc42, and Rd42is independently selected fromH, Ci-6 alkyl, and Ci-6 haloalkyl;

[0451] each Rb42is independently selected from C1-6 alkyl and C1-6 haloalkyl;

[0452] each R5is independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, ORa5, and NRc5Rd5, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, and 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0453] each Ra5, Rc5, and Rd5is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0454] heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0455] each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0456] each R5Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51. NRc51Rd51, NRc51C(O)Rb51, NRc51S(O)2Rb51, and NRc51S(O)2NRc51Rd51;

[0457] each Ra51, Rc51, and Rd51is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, and C3-7 cycloalkyl;

[0458] each Rb51is independently selected from C1-6 alkyl and C1-6 haloalkyl; and each RGis independently selected from OH, NO2, CN, halo. C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(C1-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(C1-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(C1-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(C1-3 alkyl)aminocarbonylamino.

[0459] In some embodiments:

[0460] n is 1;

[0461] p is 0, 1, 2, or 3;

[0462] each m is independently 1 or 2;

[0463] Z

[0464] Y is O or S, and Z is CR1; or

[0465]

[0466] Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0467]

[0468] , Y is CR2, and Z is O or S;

[0469] X is O, S(O)2, or N(-L-R4);

[0470] L is C(O), C(O)O, S(O)2, or S(O)2NRa;

[0471] Rais selected from H and C1-3 alkyl;

[0472] Ring moiety A is 5-9 membered heteroaryl;

[0473] when Y is O, then R1is selected from H, D, CN, halo, C1-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, and NRclRdl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0474] when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci-6 haloalky l, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl, (R1A)m-C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl. ORb1, SRb1, and NRc1Rd1, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alky l, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-Ci_6haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroary l portion of said (R1A2)m-5-6 membered heteroaryl, and (ii) the C3-7 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl are each optionally substituted by 1. 2, or 3 independently selected R1A4substituents;

[0475] each Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0476] alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0477] each Rblis independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0478] each R1Ais independently selected from halo, CN. Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyd-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11. OC(O)NRcllRd11, NRcllRd11, NRc11C(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRdn, S(O)2Rb11. and S(O)2NRcllRd11, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;

[0479] each Ral1, Rcl1, and Rdl1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroary I-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0480] each Rbl1is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalky 4, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0481] each R1Bis independently selected from halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRcl2Rd12, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRcl2Rd12;

[0482] each Ral2, Rcl2, and Rdl2is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;

[0483] each Rbl2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0484] each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)ORa11, NRc11C(O)NRc11Rd11, NRc11S(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRc11Rd11, wherein said C2-6 alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0485] each R1A2is independently selected from CN, NO2, (R1B)m-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl. (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyL 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11.

[0486] NRc11S(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0487] each R1A3is independently selected from halo, OH, and C1-4 alkoxy; and

[0488] each R1A4is independently selected from halo, OH, Ci-6 alkyl, and CM alkoxy; each Rml1is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0489] R2is selected from H, halo, CN, Ci-6 alkyl, and Ci-6 haloalky 1, wherein said Ci-6 alkyl and Ci -6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;

[0490] each R3is independently selected from C1-6 alkylene-ORa3, C1-6 alkylene-NRc3Rd3, ORa3, and NRc3Rd3;

[0491] each Ra3, Rc3. and Rd3is independently selected from H. Ci-6 alkyl, and Ci-6 haloalkyl; R4is selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, 3. or 4 independently selected R4Asubstituents;

[0492] each R4Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa41, and NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0493] each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0494] each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1 or 2 independently selected R4Bsubstituents;

[0495] each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa42and NRc42Rd42;

[0496] each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0497] each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;

[0498] each R5is independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa5, and NRc5Rd5, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalky l, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0499] each Ra5, Rc5. and Rd5is independently selected from H. Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl -C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0500] each Rb5is independently selected from C1-6 alky 1, Ci-6 haloalky l, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl -Ci -4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alky 1, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0501] each R5Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51S(O)2Rb51, and NRc51S(O)2NRc51Rd51;

[0502] each Ra51, Rc51, and Rd51is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0503] each Rb51is independently selected from C1-6 alkyl and C1-6 haloalkyl: and each RGis independently selected from OH, NO2, CN, halo, C1-3 alky 1, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alky l, C3-4 cycloalkyl, C1-3 alkoxy, C1.3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci-3 alkylthio, C1-3 alkylsulfinyl, C1.3 alkylsulfonyl, carbamyl, C1.3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alky lsulfonylamino, aminosulfonyl, C 1-3 alky laminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(C1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-3 alky laminocarbonylamino, and di(C 1-3 alkyl)aminocarbonyl amino.

[0504] In some embodiments:

[0505] n is 1;

[0506] p is 0, 1, 2, or 3;

[0507] each m is independently 1 or 2;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0508] Y is O or S, and Z is CR1; or

[0509]

[0510] , Y is CR2, and Z is O or S;

[0511] X is O, S(O)2, or N(-L-R4);

[0512] L is C(O), C(O)NRa, C(O)O, S(O), S(O)2, or S(O)2NRa;

[0513] Raand Rcare each independently selected from H and C1-3 alkyl;

[0514] or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring optionally substituted by 1 or 2 independently selected R4Asubstituents;

[0515] Ring moiety A is 5-9 membered heteroaryl;

[0516] when Y is O, then R1is selected from H, D, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alky l, and ORbl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0517] when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci-6 haloalkyl. C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl, (R1A)m-C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, and ORbl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-C1-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-C1-6 haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0518] membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl. and (ii) the C3-7 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents;

[0519] each Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0520] each Rblis independently selected from Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0521] each R1Ais independently selected from halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0522] each Ra11, Rc11, and Rd11is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky 1, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0523] membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents; each Rb11is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0524] each R1Bis independently selected from halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa12, and NRcl2Rd12;

[0525] each Ral2, Rcl2. and Rdl2is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;

[0526] each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORm11, and NRc11Rd11, wherein said C2-6 alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alky l, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0527] each R1A2is independently selected from CN, NO2, (R1B)m-Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alky 1, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORm11and NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0528] each R1A3is independently selected from halo, OH, and C1-4 alkoxy; and

[0529] each R1A4is independently selected from halo, OH, C1-6 alkyl, and C1-4 alkoxy; each Rml1is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl;

[0530] R2is selected from H, halo, CN, C1-6 alkyl, and C1-6 haloalkyl;

[0531] each R3is independently selected from C1-6 alkyl, C1-6 alkylene-OH and OH;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0532] R4is selected from H, Ci-6 alkyl. Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C3-7 cycloalkyl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C3-7 cycloalkyl-Ci-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;

[0533] each R4Ais independently selected from oxo, halo, CN, C1-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0534] each R4Bis independently selected from D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, ORa42and NRc42Rd42;

[0535] each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;

[0536] each R5is independently selected from D, halo, CN, Ci-6 alky l, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, ORa5, and NRc5Rd5, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, and 4-7 membered heterocycloalkyl-Ci-4 alkyd are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0537] each Ra5, Rc5. and Rd5is independently selected from H. Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalkyl-C1-4 alkyl, and 4-7 membered heterocycloalkyl-C 1-4 alkyl, wherein said C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalkyl-Ci-4 alkyl, and 4-7 membered heterocycloalkyl-C 1-4 alky 1 are each optionally substituted with 1, 2. 3, or 4 independently selected R5Asubstituents;

[0538] each R5Ais independently selected from D, halo, CN. Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, 4-7 membered heterocycloalkyl, ORa51, and NRc51Rd51; and

[0539] each Ra51, Rc51, and Rd51is independently selected from H, Ci-6 alkyd, Ci-6 haloalky l, and C3-7 cycloalkyl.

[0540] In some embodiments:

[0541] n is 1;

[0542] p is 0, 1, 2, or 3;

[0543] each m is independently 1 or 2;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0544] Y is O or S, and Z is CR1; or

[0545]

[0546] , Y is CR2, and Z is O or S;

[0547] X is O, S(O)2, or N(-L-R4);

[0548] L is C(O), C(O)O, S(O)2, or S(O)2NRa;

[0549] Raand Rcare each independently selected from H and C1-3 alkyl;

[0550] Ring moiety A is 5-9 membered heteroaryl;

[0551] when Y is O, then R1is selected from H, D, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, and ORbl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroar I-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0552] when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalkyd, (R1A2)m-5-6 membered heteroaryl, (R1A)m-C3-7 cycloalky I-C1-4 alkyl, phenyl-Ci-4 alky 1, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, and ORbl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci.4 alky l, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-C1-6haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, and (ii) the C3-7 cycloalkyl-C 1-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-Ci-4 alky I are each optionally substituted by 1, 2. or 3 independently selected R1A4substituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0553] each Ral, Rcl. and Rdlis independently selected from H. Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl -C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0554] each Rblis independently selected from Ci-6 alky 1, Ci-6 haloalky l, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl -Ci -4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alky 1, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;

[0555] each R1Ais independently selected from halo, CN. C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11. OC(O)NRc11Rd11, NRc11Rd11, NRcl1C(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11. and S(O)2NRcllRd11, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0556] each Ral1, Rcl1, and Rdl1is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalk l. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0557] each Rbl1is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0558] each R1Dis independently selected from halo, CN. Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa12, and NRcl2Rd12;

[0559] each Ra12, Rc12, and Rd12is independently selected from H, C1-6alkyl, and C1-6haloalkyl;

[0560] each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORm11, and NRcllRdn, wherein said C2-6 alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0561] each R1A2is independently selected from CN, NO2, (R1B)m-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalky l, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORm11and NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;

[0562] each R1A3is independently selected from halo, OH, and C1-4 alkoxy; and

[0563] each R1A4is independently selected from halo, OH, Ci-6 alkyl, and CH alkoxy; each Rml1is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl;

[0564] R2is selected from H, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl;

[0565] each R3is independently selected from Ci-6 alkyd ene-OH and OH;

[0566] R4is selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalky 1, pheny l, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0567] heteroaryl are each optionally substituted by 1, 2, 3. or 4 independently selected R4Asubstituents;

[0568] each R4Ais independently selected from halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;

[0569] each R4Dis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkvl. ORa42and NRc42Rd42;

[0570] each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;

[0571] each R5is independently selected from D, halo, CN. Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa5, and NRc5Rd5, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0572] each Ra5, Rc5. and Rd5is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalky l, C3-7 cycloalkyl-C 1-4 alkyl, and 4-7 membered heterocycloalkyl-C 1-4 alkyl, wherein said C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalky I-C1-4 alky l, and 4-7 membered heterocycloalkyl-C 1-4 alkyd are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;

[0573] each R5Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, Ci-6 haloalkyl, ORa51, and NRc51Rd51; and

[0574] each Ra51, Rc51, and Rd51is independently selected from H, Ci-6 alkyd, and Ci-6 haloalkyl.

[0575] In some embodiments, the compound is a compound of Formula (II):

[0576]

[0577] or a pharmaceutically acceptable salt thereof.

[0578] In some embodiments, the compound is a compound of Formula (III):Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0579]

[0580] or a pharmaceutically acceptable salt thereof.

[0581] In some embodiments, the compound is a compound of Formula (IV):

[0582]

[0583] or a pharmaceutically acceptable salt thereof.

[0584] In some embodiments, the compound is a compound of Formula (V):

[0585]

[0586] or a pharmaceutically acceptable salt thereof.

[0587] In some embodiments, the compound is selected from:

[0588] (37?,4A)-4-((6-(l / f-pyrazol-4-yl)thieno[3,2-< |pyrimidin-2-yl)amino)-l- (methylsulfonyl)piperidin-3-ol;

[0589] (3J?,4J?)-4-((6-(3-methyl-17f-pyrazol-4-yl)thieno[3,2-< / |pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;

[0590] (37?,47?)-4-((6-(17f-pyrazol-4-yl)thieno[3,2-t / ]pyriinidin-2-yl)amino)-l-(cyclopropylsulfonyl)piperidin-3-ol;

[0591] (3,47?)-4-((6-(17 / -pyrazol-4-yl)thieno[2,3-t / ]pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0592] (3R, 4 )-4-((6-(l / 7-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-l-((l -methyl- 1 / 7-pyrazol-4-yl)sulfonyl)piperidin-3-ol;

[0593] (3?,4?)-4-((6-(l / 7-pyrazol-4-yl)thieno[3,2-< / ]pyrimidin-2-yl)amino)-l-((l-methyl-177-pyrazol-3-yl)sulfonyl)piperidin-3-ol;

[0594] l-((37?,47?)-3-hydroxy-4-((6-(pyridazin-4-yl)thieno[3,2-t / ]pyrimidin-2-yl)amino) piped din- 1 -y l)ethan- 1 -one;

[0595] (35,47?)-4-((6-(17 / -pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)tetrahydro-27 / -pyran-3-ol;

[0596] (35.47?)-4-((7-(4-(azetidin-l-ylmethyl)-3-fluorophenyl)-6-(177-pyrazol-4-yl)thieno[3,2-d|pyrimidin-2-yl)amino)tetrahydro-2 / 7-pyran-3-ol;

[0597] (35,4?)-4-((7-(2-((isopropylanuno)methyl)pyridin-4-yl)-6-(177-pyrazol-4-yl)thieno[3,2- ]pyrimidin-2-yl)amino)tetrahydro-2 / 7-pyran-3-ol;

[0598] (35,47?)-4-((6-(l / 7-pyrazol-4-yl)-7-(((5)-pyrrolidin-2-yl)ethynyl)thieno[3,2- <7|pyrimidin-2-yl)amino)tetrahydro-2 / f-pyran-3-ol;

[0599] (35.47)-4-((6-(l / 7-pyrazol-4-yl)-7-(pyridin-4-ylethynyl)thieno[3,2-t / ]pyrimidin-2-yl)amino)tetrahydro-277-pyran-3-ol;

[0600] (35, 4?)-4-((7-(azetidin-3-yl)-6-(l 7-pyrazol-4-yl)thieno[3,2-<7]pyrimi din-2-yl)amino)tetrahydro-2 / 7-pyran-3-ol;

[0601] (35.4?)-4-((6-(l / 7-pyrazol-4-yl)-7-(((7?)-pyrrolidin-3-yl)methyl)thieno[3,2-d\ py rimi din-2-y 1 )amino)tetrahy dro-277-py ran-3 -ok

[0602] (37?,4?)-4-((6-(l / 7-pyrazol-4-yl)furo[3,2-<7]pyrimidin-2-yl)amino)-l- (methylsulfonyl)piperidin-3-ol;

[0603] (3 / .4 / )-l-(methylsullbnyl)-4-((6-(pyndin-4-yl)thieno|3.2-t / |pyrimidin-2-yl)amino)piperidin-3-ol;

[0604] (3?,4?)-l-(methylsulfonyl)-4-((6-(thiazol-5-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)piperidin-3-ol;

[0605] (377, 47?)-4-((6-(3-(difluoromethyl)-l / 7-pyrazol-4-yl)thieno[3,2-cf]pyrimi din-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;

[0606] methyl (37?,47?)-4-((6-(3-(azetidin-3-ylmethoxy)-l 7-pyrazol-4-yl)thieno[3,2-<7|pyrimidin-2-yl)amino)-3-hydroxypiperidine-l -carboxylate;

[0607] (35,47?)-4-((7-ethoxy-6-(177-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)tetrahydro-277-pyran-3-ol;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0608] (35.47?)-4-((7-(2-(dimethylamino)ethoxy)-6-(177-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)tetrahydro-27 / -pyran-3-ol;

[0609] ethyl (37?,47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)-3-hydroxypiperidine-1 -carboxylate;

[0610] ((37?,47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hy droxypiperidin- 1 -yl)(cyclopropyl)methanone;

[0611] (37?,47?)-3-hydroxy-2V,2V-dimethyl-4-((6-(6-methyl-l / 7-indazol-5-yl)thieno[2,3-<7]pyrimidin-2-yl)amino)piperidine-l -sulfonamide;

[0612] cyclopropyl((37?,47?)-4-((6-(6-fluoro-5-hydroxy-3-methylpyridin-2-yl)thieno[2,3-<7|pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)methanone;

[0613] cyclopropyl((37?,47?)-4-((6-(3-((dimethylamino)methyl)-177-pyrazol-4-yl)thieno[3,2- <7|pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)methanone; and

[0614] (3S,47?)-4-((7-(4-isopropylpiperazin-l-yl)-6-(177-pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)tetrahydro-277-pyran-3-ol;

[0615] or a pharmaceutically acceptable salt thereof.

[0616] In some embodiments, the compound is selected from:

[0617] (3 / ?.4 / ?)-4-((6-(l-methyl- l / 7-pyrazol-4-yl)thieno|3.2-c / |pyrimidin-2-yl)amino)-l -(methylsulfonyl)piperidin-3-ol;

[0618] (37?, 47?)-4-((6-(3-fluoro-177-pyrazol-4-yl)thieno[3.2-<7]pyrimi din-2 -yl)amino)-l-(methylsulfonyl)piperidin-3-ol;

[0619] (37?,47?)-4-((6-(3-methoxy-177-pyrazol-4-yl)thieno[3,2-<7|pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;

[0620] (37?, 47?)-4-((6-(3-cyclopropyl-177-pyrazol-4-yl)thieno[3.2-t / ]pyrimi din-2 -yl)amino)-l-(methylsulfonyl)piperidin-3-ol;

[0621] (37?,47?)-4-((6-(3-isopropyl-177-pyrazol-4-yl)thieno[3,2-tf]pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;

[0622] (37?,47?)-4-((6-(3-ethyl-lH-pyrazol-4-yl)thieno[3,2-6f]pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;

[0623] (37?,47?)-l-(methylsulfonyl)-4-((6-(pyridazin-4-yl)thieno[3,2-< / |pyrimidin-2-yl)amino)piperidin-3-ol;

[0624] (37?,47?)-l-(methylsulfonyl)-4-((6-(pyridin-3-yl)thieno[3,2-t / |pyrimidin-2-yl)amino)piperidin-3-ol;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0625] (3R.47?)-4-((6-(isothiazol-4-yl)thieno[3,2-<7]pyrirni din-2 -yl)amino)- 1-(methylsulfonyl)piperidin-3-ol;

[0626] ((37?, 47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-< ]pyrimi din-2 -yl)amino)-3-hydroxypiperidin- 1 -yl)(l -methylcyclopropyl)methanone;

[0627] ((37?,47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;

[0628] 1 -((37?,47?)-4-((6-(1 7-pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)-3-hy droxypiperidin- 1 -y l)butan- 1 -one;

[0629] l-((37?,47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-<7|pyrimidin-2-yl)amino)-3-hy droxypiperidin- 1 -y l)ethan- 1 -one;

[0630] methyl (37?,47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-<7|pyrimidin-2-yl)amino)-3-hy droxypiperidine- 1 -carboxylate;

[0631] ((37?, 47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-ri]pyrirni din-2 -yl)amino)-3-hy droxypiperidin- 1 -yl)(l -(difluoromethyl)cy clopropy l)methanone;

[0632] l-((37?,47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-(7]pyrimidin-2-yl)amino)-3-hydroxypiperi din-1 -yl)-4,4,4-trifluorobutan-l -one;

[0633] l-((37?,47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)-2-methylpropan-l-one;

[0634] ((37?,47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)(cyclobutyl)methanone;

[0635] ((37?,47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1 -yl)(l -methylcyclobutyl )methanone;

[0636] ((3R, 4R)-4-((6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperidin-1 -yl)(l -fluorocyclobutyl)methanone;

[0637] (3R,4R)-4-((6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-l-(ethylsulfonyl)piperidin-3-ol;

[0638] ((3R,4R)-4-((6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperidin-1 -y 1)( 1 -(1.1 -difluoroethyl)cy clopropy l)methanone;

[0639] ((3R,4R)-4-((6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)-3-hy droxypiperi din-1 -yl)((l S,2R)-2-fluorocyclopropyl)methanone;

[0640] ((3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)((1R,2S)-2-fluorocyclopropyl)methanone;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0641] (( 3R, 47?)-4-((7-ethoxy-6-(17 / -pyrazol-4-yl)thieno[3,2-< / ]pyrimi din-2 -yl)amino)-3-hy droxypiperi din-1 -yl)(( 15, 27?)-2-fluorocyclopropyl)methanone;

[0642] ((37?,47?)-4-((7-ethoxy-6-(177-pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)((17?,25)-2-fluorocyclopropyl)methanone;

[0643] cyclopropyl((3?,47?)-4-((7-ethoxy-6-(177-pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)methanone;

[0644] ((37?, 47?)-4-((7-ethoxy-6-(177-pyrazol-4-yl)thieno[3,2-< ]pyri midin-2 -yl)amino)-3-hydroxypiperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)rnethanone;

[0645] (l-(difluoromethyl)cyclopropyl)((37?,47?)-4-((7-ethoxy-6-(177-pyrazol-4-yl)thieno[3,2-t / |pyrimi din-2 -yl)amino)-3-hydroxypiperi din- 1 -yl)methanone;

[0646] 1-((37?,47?)-4-((7-ethoxy-6-(177-pyrazol-4-yl)thieno[3,2-(7]pyrimidin-2-yl)amino)-3-hy droxypiperidin- 1 -y l)butan- 1 -one;

[0647] 2-cyclopropyl-l-((3R,4R)-4-((7-Ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2-y l)amino)-3-hy droxypiperidin- 1 -yl)ethan- 1 -one;

[0648] l-((3R,4R)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3.2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)-3,3-difluoropropan-l-one;

[0649] ((3R,4R)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hy droxypiperi din-1 -yl)(3-fluorobicyclo[l.1.1 ] pentan- 1 -yl)methanone;

[0650] ((3R,4R)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3.2-d]pyrimidin-2-yl)amino)-3-hy droxypiperi din-1 -yl)(tetrahydro-2H-pyran-4-yl)methanone;

[0651] (l,l-dioxidothietan-3-yl)((3R,4R)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)methanone;

[0652] (l-(difluoromethyl)cyclopropyl)((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)piperi din- 1 -yl)methanone;

[0653] ((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2-yl)arruno)piperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;

[0654] ((lS,2R)-2-fluorocyclopropyl)((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thi eno[3,2-d]pyrimi din-2 -yl)amino)piperi din- 1 -y l)methanone;

[0655] cyclopropyl((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)piperidin-l-yl)methanone;

[0656] l-((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2-y l)amino)piperidin- 1 -y l)butan- 1 -one;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0657] ((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l -yl)(l -methylcyclopropyl)methanone;

[0658] (3,3-difluorocyclobutyl)((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;

[0659] (3-fluorobicyclo[l.l.l]pentan-l-yl)((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;

[0660] ethyl (3 / ?,47?)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-t / ]pyrimidin-2-yl)amino)-3-hydroxypiperidine-1 -carboxylate;

[0661] ((3R,4R)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hy droxypiperidin- 1 -yl)(morpholino)methanone;

[0662] methyl (3R,4S)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-methylpiperidine-l -carboxylate;

[0663] cyclopropyl((3R,4S)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2-yl)amino)-3-methylpiperidin-l-yl)methanone;

[0664] (3,3-difluoroazetidin-l-yl)((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3, 2-d]pyrimi din-2 -yl)amino)piperidin-l-yl)methanone;

[0665] 6-(2-(((3<S',4?)-3-hydroxytetrahydro-2 / f-pyran-4-yl)amino)thieno[2,3-<7]pyrimidin-6-yl)-2-methoxypyridin-3-ol;

[0666] 2-ethoxy-6-(2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)thieno[2,3-d]pyrimidin-6-yl)pyridin-3-ol;

[0667] 6-(2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)thieno[2,3-d]pyrimi din-6-y l)-2-methylpyri din-3 -ol;

[0668] 6-(2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)thieno[2,3-d]pyrimi din-6-yl)-2-methoxy-5-methylpyridin-3-ol;

[0669] 6-(2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)thieno[2,3-d]pyrimi din-6-y l)-2-(methyl amino)py ri din-3 -ol;

[0670] cyclopropyl((37?,47?)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-<7|pyrimidin-2-yl)amino)piperidin- 1 -yl)methanone;

[0671] cyclopropyl((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;

[0672] methyl (3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidine-l -carboxylate;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0673] ethyl (3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidine-l -carboxylate;

[0674] l-((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)-2-methylpropan-l-one;

[0675] l-((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2.3-d] py rimidin-2-yl)amino)piperidin- 1 -yl)ethan- 1 -one;

[0676] l-((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)butan-l-one;

[0677] ((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin- 2-y l)amino)piperidin- 1 -yl)(l -(trifluoromethyl)cyclopropy l)methanone;

[0678] ((lS,2R)-2-fluorocyclopropyl)((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;

[0679] ((lR,2S)-2-fluorocyclopropyl)((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2.3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;

[0680] (l-(difluoromethyl)cyclopropyl)((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;

[0681] (3-fluorobicyclo[l.1. l]pentan- l-yl)((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;

[0682] 3-((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2.3-d]pyrimidin-2-yl)amino)piperidine-l -carbonyl)bicyclo[ 1.1. l]pentane-l -carbonitrile;

[0683] (2-oxabicyclo[2.1. l]hexan-4-yl)((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;

[0684] ethyl (3R,4R)-4-((6-(3-([1,3'-biazetidin]-1'-yl)-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidine-1-carboxylate;

[0685] ethyl (3R,4R)-4-((6-(3-(3-(dimethylamino)azetidin-l-yl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidine-l -carboxylate;

[0686] ethyl (3R,4R)-3-hydroxy-4-((6-(3-(4-methylpiperazin-l-yl)-lH-pyrazol-4-yl)thi eno[3,2-d]pyrimi din-2 -yl)amino)piperi dine- 1 -carboxylate;

[0687] ethyl (3R,4R)-3-hydroxy-4-((6-(3-(3-(pyrrolidin-l-yl)azetidin-l-yl)-lH-pyrazol-4-yl)thi eno[3,2-d]pyrimi din-2 -yl)amino)piperidine-l -carboxylate;

[0688] ethyl (3R,4R)-4-((6-(3-((R)-3-(dimethylamino)pyrrolidin-l-yl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperidine-l -carboxylate;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0689] ethyl (3R,4R)-4-((6-(3-((S)-3-(dimethylamino)pyrrolidin-l-yl)-lH-pyrazol-4-yl)thi eno[3,2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperidine-l -carboxylate;

[0690] ethyl (3R,4R)-4-((6-(3-((dimethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperidine-l-carboxylate;

[0691] ethyl (3R,4R)-4-((6-(3-((ethylamino)methyl)-lH-pyrazol-4-yl)thieno[3.2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidine-l -carboxylate;

[0692] ((3R,4R)-4-((6-(3-((dimethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;

[0693] ((3R,4R)-4-((6-(3-((ethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyri mi din-2-yl)amino)-3-hydroxypiperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;

[0694] 2,2-difluoroethyl (3R,4R)-4-((6-(3-((dimethylamino)methyl)-lH-pyrazol-4-yl)thi eno[3,2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperidine-l -carboxylate;

[0695] (3R,4R)-4-((6-(3-((dimethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;

[0696] (3R,4R)-4-((6-(3-((ethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)- 1 -(methyl sulfonyl)piperidin-3-ol;

[0697] cyclopropyl((3R,4R)-4-((6-(3-((ethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)methanone;

[0698] (3R,4R)-4-((6-(3-(azetidin-l-ylmethyl)-lH-pyrazol-4-yl)thieno[3.2-d]pyrimidin-2-yl)amino)- 1 -(methyl sulfonyl)piperidin-3-ol;

[0699] methyl (3R,4R)-3-hydroxy-4-((6-(3-((methylamino)methyl)-lH-pyrazol-4-yl)thi eno[3,2-d]pyrimi din-2 -yl)amino)piperidine-l -carboxylate;

[0700] methyl (3R,4R)-4-((6-(3-((ethylamino)methyl)-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidine-1-carboxylate;

[0701] ((3R,4R)-4-((6-(3-((cyclobutylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;

[0702] ((3R,4R)-3-hydroxy-4-((6-(3-((isopropylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;

[0703] ((3R,4R)-4-((6-(3-((ethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyri midin-2-yl)amino)-3-hydroxypiperidin-l-yl)(l-fluorocyclobutyl)methanonetrifluoromethyl)cyclopropyl)methanone;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0704] ethyl (3R,4R)-3-hydroxy-4-((6-(3-(1-methylpyrrolidin-3-yl)-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidine-1-carboxylate;

[0705] ((3R,4R)-3-hydroxy-4-((6-(3-(l-methylazetidin-3-yl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;

[0706] 4,4,4-trifluoro-l-((3R,4R)-3-hydroxy-4-((6-(3-(l-methylazetidin-3-yl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)piperi din- 1 -yl)butan- 1 -one;

[0707] ethyl (3R,4R)-3-hydroxy-4-((6-(3-(l -methylazetidin-3-yl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidine-l -carboxylate; and

[0708] (l-fluorocyclobutyl)((3R,4R)-3-hydroxy-4-((6-(3-(l-methylpyrrolidin-3-yl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;

[0709] or a pharmaceutically acceptable salt thereof.

[0710] In some embodiments, 1, 2, 3, 4, 5, 6, 7, or 8 hydrogen atoms, attached to carbon atoms of “alkyl”, “alkenyl”, “alkynyl”, “aryl”, “phenyl”, “cycloalkyl”, “heterocycloalkyl”, or “heteroaryl” substituents or “-Ci-4 alkyd-” and “alkylene” linking groups, as described herein, are optionally replaced by deuterium atoms.

[0711] It is further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment as if the embodiments were claims written in multiple dependent form. Conversely, various features of the invention which are. for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination.

[0712] At various places in the present specification, divalent linking substituents are described. Unless otherwise specified, it is specifically intended that each divalent linking substituent include both the forward and backward forms of the linking substituent. For example, -NR(CR’R”)n- includes both -NR(CR’R”)n- and -(CR’R”)nNR-. Where the structure clearly requires a linking group, the Markush variables listed for that group are understood to be linking groups.

[0713] The term “n-membered” where n is an integer typically describes the number of ringforming atoms in a moiety where the number of ring-forming atoms is n. For example, piperidinyl is an example of a 6-membered heterocycloalkyl ring, pyrazolyl is an example of a 5 -membered heteroaryl ring, pyridyl is an example of a 6-membered heteroaryl ring, and 1,2,3,4-tetrahydro-naphthalene is an example of a 10-membered cycloalkyl group.

[0714] As used herein, the phrase “optionally substituted” means unsubstituted or substituted. The substituents are independently selected, and substitution may be at any chemicallyAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0715] accessible position. As used herein, the term "substituted" means that a hydrogen atom is removed and replaced by a substituent. A single divalent substituent, e.g., oxo, can replace two hydrogen atoms. It is to be understood that substitution at a given atom is limited by valency, that the designated atom’s normal valency is not exceeded, and that the substitution results in a stable compound.

[0716] As used herein, the term “independently selected from” means that each occurrence of a variable or substituent are independently selected at each occurrence from the applicable list.

[0717] As used herein, the phrase “each ‘variable’ is independently selected from” means substantially the same as wherein “at each occurrence ‘variable’ is selected from.” When any variable (e.g., RG) occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 1, 2, 3, or 4 independently selected RGsubstituents, then said group may optionally be substituted with up to four RGgroups and RGat each occurrence is selected independently from the definition of RG.

[0718] In some embodiments, substituents are indicated as floating substituents — e.g., (R3)n in Formula (I):

[0719]

[0720] It is understood that substituent R3can occur n number of times on the ring, and R3can be a different moiety at each occurrence. It is to be understood that each R group may replace any hydrogen atom attached to a ring atom, except that R3may not replace -L-R4in the variable X. (R5)pis another example of a floating substituent.

[0721] Throughout the definitions, the term “Cn-m” indicates a range which includes the endpoints, wherein n and m are integers and indicate the number of carbons. Examples include C1-3, C1-4, Ci-6, and the like.

[0722] As used herein, the term “Cn-m alkyd”, employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chain or branched, havingAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0723] n to m carbons. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl (Me), ethyl (Et), / 7-propyl ( / 7-Pr). isopropyl (z-Pr), zr-butyL tert-butyl, isobutyl, sec-butyl; higher homologs such as 2-methy 1-1 -butyl, w-pentyl, 3-pentyl, w-hexyl, 1,2,2-trimethylpropyl, and the like. In some embodiments, the alkyl group contains from 1 to 6 carbon atoms, from 1 to 4 carbon atoms, from 1 to 3 carbon atoms, or 1 to 2 carbon atoms.

[0724] As used herein. (R1A1)m-C1-6alkyl refers to a saturated hydrocarbon group that may be straight-chain or branched, having 1 -6 carbons, wherein the hydrocarbon group is substituted by m independently selected R1A1substitutents.

[0725] As used herein, (R1B)m-Ci-6 alkyl refers to a saturated hydrocarbon group that may be straight-chain or branched, having 1-6 carbons, wherein the hydrocarbon group is substituted by m independently selected R1Bsubstitutents.

[0726] As used herein, “Cn-m alkenyl” refers to an alkyl group having one or more double carbon-carbon bonds and having n to m carbons. Example alkenyl groups include, but are not limited to, ethenyl, / ?-propenyl. isopropenyl, / ?-butenyl. sec-butenyl, and the like. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0727] As used herein, “Cn-malkynyl” refers to an alkyl group having one or more triple carbon-carbon bonds and having n to m carbons. Example alkynyl groups include, but are not limited to, ethynyl, propyn-l-yl, propyn-2-yl, and the like. In some embodiments, the alkynyl moiety contains 2 to 6. 2 to 4, or 2 to 3 carbon atoms.

[0728] As used herein, the term '‘Cn-m alkoxy”, employed alone or in combination with other terms, refers to a group of formula-O-alkyl, wherein the alkyl group has n to m carbons. Example alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), butoxy (e.g., M-butoxy and zm-buloxy ). and the like. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0729] As used herein, (R1B)m-Ci-4 alkoxy refers to a group of formula-O-alkyl, wherein the alkyl group has 1-4 carbons., wherein the alkyl group is substituted by m independently selected R1Bsubstitutents.

[0730] As used herein, the term “amino” refers to a group of formula -NH2.

[0731] As used herein, the term “aryl,” employed alone or in combination with other terms, refers to an aromatic hydrocarbon group, which may be monocyclic or polycyclic (e.g., having 2 fused rings). The term “Cn-m aryl” refers to an aryl group having from n to m ring carbon atoms. In some embodiments, the aryl group has 6 to 10 carbon atoms. In some embodiments, the aryl group is phenyl or naphthyl. In some embodiments, the aryl is phenyl.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0732] As used herein, "halo" refers to F, Cl, Br, or I. In some embodiments, halo is F. Cl. or Br. In some embodiments, halo is F or Cl. In some embodiments, halo is F. In some embodiments, halo is Cl.

[0733] As used herein, “Cn-m haloalkoxy” refers to a group of formula -O-haloalkyl having n to m carbon atoms. Example haloalkoxy groups include OCF3 and OCHF2. In some embodiments, the haloalkoxy group is fluorinated only. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0734] As used herein, the term “Cn-m haloalkyl,” employed alone or in combination with other terms, refers to an alkyl group having from one halogen atom to 2s+l halogen atoms which may be the same or different, where “s” is the number of carbon atoms in the alkyl group, wherein the alkyl group has n to m carbon atoms. In some embodiments, the haloalkyl group is fluorinated only. In some embodiments, the alkyl group of the haloalkyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. Example haloalky l groups include CF3, C2F5, CHF2, CH2F, CCh. CHCI2. C2CI5 and the like.

[0735] As used herein, (R1A1)m-Ci-6 haloalkyl refers to a haloalkyl group, having 1-6 carbons, wherein the haloalkyl group is substituted by m independently selected R1A1substitutents.

[0736] As used herein, the term “thio” refers to a group of formula -SH.

[0737] As used herein, the term “Cn-m alkylamino” refers to a group of formula -NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylamino has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0738] As used herein, the term “Cn-m alkoxy carbonyl” refers to a group of formula -C(O)O-alkyl, wherein the alky l group has n to m carbon atoms. In some embodiments, the alkyl group of the alkoxy carbonyl has 1 to 6, 1 to 4. or 1 to 3 carbon atoms.

[0739] As used herein, the term “Cn-m alkydcarbonyl” refers to a group of formula -C(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylcarbonyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0740] As used herein, the term “Cn-malkylcarbonylamino” refers to a group of

[0741] formula -NHC(O)-alkyl. wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylcarbonylamino has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0742] As used herein, the term “Cn-malkoxy carbony lamino” refers to a group of formula -NHC(0)0(Cn-m alkyl), wherein the alkyl group has n to m carbon atoms. In someAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0743] embodiments, the alkyl group of the alkoxycarbonylamino has 1 to 6. 1 to 4, or 1 to 3 carbon atoms.

[0744] As used herein, the term “Cn-m alkylsul fonylamino” refers to a group of formula -NHS(O)2-alkyl, wherein the alky l group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylsulfonylamino has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0745] As used herein, the term '‘aminosulfonyl” refers to a group of formula -S(O)2NH2. As used herein, the term “Cn-m alkylaminosulfonyl” refers to a group of formula -S(O)2NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylaminosulfonyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0746] As used herein, the term “di(Cn-m alkylaminosulfonyl” refers to a group of formula -S(O)2N(alkyl)2, wherein each alkyl group independently has n to m carbon atoms. In some embodiments, each alkyl group of the dialkylaminosulfonyl has, independently, 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0747] As used herein, the term '‘aminosulfonylamino” refers to a group of formula -NHS(O)2NH2.

[0748] As used herein, the term “Cn-m alkylaminosulfonylamino” refers to a group of formula -NHS(O)2NH(alkyl). wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylaminosulfonylamino has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0749] As used herein, the term “di(Cn-m alkyl)aminosulfonylamino” refers to a group of formula -NHS(O)2N(alkyl)2, wherein each alkyl group independently has n to m carbon atoms. In some embodiments, each alkyl group of the dialkylaminosulfonylamino has, independently, 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0750] As used herein, the term “aminocarbonyl amino,” employed alone or in combination with other terms, refers to a group of formula -NHC(O)NH2.

[0751] As used herein, the term “Cn-malkylaminocarbonylamino” refers to a group of formula -NHC(O)NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylaminocarbonylamino has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0752] As used herein, the term “di(Cn-m alkyl)aminocarbonylamino” refers to a group of formula -NHC(O)N(alkyl)2, wherein each alkyl group independently has n to m carbonAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0753] atoms. In some embodiments, each alkyl group of the dialkylaminocarbonylamino has, independently, 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0754] As used herein, the term “Cn-m alky I carbam l" refers to a group of formula -C(O)-NH(alkyl), wherein the alky l group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylcarbamyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0755] As used herein, the term “Cn-malkydthio’7refers to a group of formula -S-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylthio has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0756] As used herein, the term “Cn-malk lsulfiny l" refers to a group of formula -S(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylsulfinyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0757] As used herein, the term “Cn-m al ky Isul fony I" refers to a group of formula -S(O)2-alkyl, wherein the alky l group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylsulfonyl has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0758] As used herein, the term “cyano-Cn-m alkyl” refers to a group of formula -(Cn-m alkylene)-CN, wherein the alkylene group has n to m carbon atoms. As used herein, the term “cyano-Ci-6 alkyl” refers to a group of formula -(Ci-6 alky lene)-CN. As used herein, the term “cyano-Ci-3 alkyl” refers to a group of formula -(C1-3 alkylene)-CN.

[0759] As used herein, the term “HO-Cn malkyl” refers to a group of formula -(Cn-malkylene)-OH, wherein the alkylene group has n to m carbon atoms. As used herein, the term “HO-C1-3 alkyl” refers to a group of formula -(C1-3 alkylene)-OH.

[0760] As used herein, the term “Cn-malkoxy-Co-Palkyl” refers to a group of formula -(Cn-malkylene)-O(Co-palkyl), wherein the alkylene group has n to m carbon atoms and the alkyl group has 0 to p carbon atoms. As used herein, the term “C1-6 alkoxy -C1-6 alkyl” refers to a group of formula -(C1-6 alky lene)-O(C 1-6 alkyl). As used herein, the term “C1-3 alkoxy-Ci-3 alkyd” refers to a group of formula -(C1-3 alkyd ene)-O(C 1-3 alkyl).

[0761] As used herein, the term “carboxy” refers to a group of formula -C(O)OH.

[0762] As used herein, the term “di(Cn-m-alkyl)amino” refers to a group of formula -N(alkyl)2, wherein the two alkyl groups each has, independently, n to m carbon atoms. In some embodiments, each alkyl group of the dialkylamino independently has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0763] As used herein, the term “di(Cn-m-alkyl)carbamyl” refers to a group of formula -C(O)N(alkyl)2, wherein the two alkyl groups each has, independently, n to m carbon atoms.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0764] In some embodiments, each alkyl group of the dialkylcarbamyl independently has 1 to 6. 1 to 4, or 1 to 3 carbon atoms.

[0765] As used herein, the term “Cn-m alkylcarbonyloxy” is a group of formula -OC(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylcarbonyloxy has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0766] As used herein, '“aminocarbonyloxy” is a group of formula -OC(O)-NH2.

[0767] As used herein, “Cn-malkylaminocarbonyloxy” is a group of formula -OC(O)-NH-alkyl. wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group of the alkylaminocarbonyloxy has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0768] As used herein. ““di(Cn-malkyl)aminocarbonyloxy” is a group of formula -OC(O)-N(alkyl)2, wherein each alkyl group has, independently, n to m carbon atoms. In some embodiments, each alkyl group of the dialkylaminocarbonyloxy independently has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0769] As used herein “Cn-m alkoxy carbonylamino” refers to a group of formula -NHC(O)-O-alkyl, wherein the alkyl group has n to m carbon atoms.

[0770] As used herein, the term “‘carbamyl” to a group of formula -C(O)NH2.

[0771] As used herein, the term “carbonyl,” employed alone or in combination with other terms, refers to a -C(O)- group.

[0772] As used herein, “cycloalky refers to non-aromatic cyclic hydrocarbons including cyclized alkyl and alkenyl groups. Cycloalkyl groups can include mono- or polycyclic (e.g., having 2, 3 or 4 fused rings) groups, spirocycles, and bridged rings (e.g., a bridged bicycloalkyl group). Ring-forming carbon atoms of a cycloalky l group can be optionally substituted by oxo or sulfido (e.g., C(O) or C(S)). Also included in the definition of cycloalkyl are moieties that have one or more aromatic rings fused (i.e., having a bond in common with) to the cycloalkyl ring, for example, benzo or thienyl derivatives of cyclopentane, cyclohexane, and the like. A cycloalkyl group containing a fused aromatic ring can be attached through any ring-forming atom including a ring-forming atom of the fused aromatic ring. Cycloalkyl groups can have 3, 4, 5. 6, 7, 8, 9, or 10 ring-forming carbons (i.e., C3-10). In some embodiments, the cycloalkyl is a C3-10 monocyclic or bicyclic cycloalkyl. In some embodiments, the cycloalkyl is a C3-7 monocyclic cycloalkyl. In some embodiments, the cycloalkyl is a C4-7 monocyclic cycloalky l. In some embodiments, the cycloalkyl is a C4-10 spirocycle or bridged cycloalkyl (e.g., a bridged bicycloalkyl group). Example cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0773] cyclohexenyl, cyclohexadienyl, cycloheptatrienyl, norbornyl, norpinyl, norcamyl, cubane, adamantane, bicyclo[l.l.l]pentyl, bicyclo[2.1.1]hexyl, bicyclo[2.2. l]heptanyl, bicyclo[3.1.1]heptanyl, bicyclo[2.2.2]octanyl, spiro[3.3]heptanyl, and the like. In some embodiments, cycloalky l is cyclopropyl, cyclobutyl. cyclopentyl, or cyclohexyl.

[0774] As used herein. (R1B)m-C3-7 cycloalkyl refers to a cycloalkyl moiety having 3-7 carbon atoms, wherein the cycloalkyl moiety is substituted by m independently selected R1Bsubstitutents.

[0775] As used herein, “heteroaryl” refers to a monocyclic or polycyclic (e.g., having 2, 3, or 4 fused rings) aromatic heterocycle having at least one heteroatom ring member selected from N, O, or S. In some embodiments, any ring-forming N in a heteroaryl moiety can be an N-oxide. In some embodiments, the heteroaryl is a 5-10 membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected fromN, O, and S. In some embodiments, the heteroaryl is a 5-6 monocyclic heteroaryl having 1 or 2 heteroatom ring members independently selected from N, O, and S. In some embodiments, the heteroaryl group contains 5 to 10 or 5 to 6 ring-forming atoms. In some embodiments, the heteroaryl group has 1 to 4 ring-forming heteroatoms, 1 to 3 ring-forming heteroatoms, 1 to 2 ring-forming heteroatoms or 1 ring-forming heteroatom. When the heteroaryl group contains more than one heteroatom ring member, the heteroatoms may be the same or different. Example heteroaryl groups include, but are not limited to, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, pyrazolyl, azolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, fury l, thienyl, triazolyl (e.g., 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl), tetrazolyl, thiadiazolyl (e.g., 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl). quinolinyl. isoquinolinyl, indolyl, benzothienyl, benzofuranyl, benzisoxazolyl, imidazo[l,2-b]thiazolyl, purinyl. triazinyl, thieno[3,2-b]pyridinyl, imidazo[l,2-a]pyridinyl, 1,5-naphthyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, oxadiazolyl (e.g., 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl), l,2-dihydro-l,2-azoborinyl, and the like.

[0776] As used herein, (R1A2)m-5-14 membered heteroaryl refers to a heteroaryl moiety having 5-14 ring members, wherein the heteroaryl moiety is substituted by m independently selected R1A2substitutents.

[0777] As used herein, “heterocycloalkyl” refers to monocyclic or polycyclic heterocycles having at least one non-aromatic ring (saturated or partially unsaturated ring), wherein one or more of the ring-forming carbon atoms of the heterocycloalkyl is replaced by a heteroatom selected from N, O, or S, and wherein the ring-forming carbon atoms and heteroatoms of theAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0778] heterocycloalkyl group can be optionally substituted by one or more oxo or sulfido (e.g., C(O), S(O), C(S), or S(O)2, etc.). Heterocycloalkyl groups include monocyclic and polycyclic (e.g., having 2 fused rings) systems. Included in heterocycloalkyl are monocyclic and polycyclic 4-10-, 4-7-, and 5-6-membered heterocycloalkyl groups. Heterocycloalkyl groups can also include spirocycles and bridged rings. The heterocycloalkyl group can be attached through a ring-forming carbon atom or a ring-forming heteroatom. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyd group contains 0 to 2 double bonds.

[0779] Also included in the definition of heterocycloalkyl are moieties that have one or more aromatic rings fused (i.e., having a bond in common with) to the non-aromatic heterocyclic ring, for example, benzo or thienyl derivatives of piperidine, morpholine, azepine, etc. A heterocycloalkyl group containing a fused aromatic ring can be attached through any ringforming atom including a ring-forming atom of the fused aromatic ring. In some embodiments, the heterocycloalkyl group contains 4 to 10 ring-forming atoms, 4 to 7 ringforming atoms, 4 to 6 ring-forming atoms or 5 to 6 ring-forming atoms. In some embodiments, the heterocycloalkyl group has 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms or 1 heteroatom.

[0780] In some embodiments, the heterocycloalkyl is a 4-10 membered monocyclic, bicyclic, or tricyclic heterocycloalkyl having 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S, wherein 1, 2, 3, or 4 ring-forming carbon or heteroatoms can be optionally substituted by one or more oxo or sulfido. In some embodiments, the heterocycloalky 1 is a 4-10 membered bicyclic heterocycloalkyl having 1, 2, 3, or 4 ringforming heteroatoms independently selected fromN, O. and S, wherein 1, 2, 3, or 4 ringforming carbon or heteroatoms can be optionally substituted by one or more oxo or sulfido. In some embodiments, the heterocycloalkyl is a 4-7 membered monocyclic heterocycloalkyl having 1 or 2 ring-forming heteroatoms independently selected from N, O, and S, and wherein 1, 2 or 3 ring-forming carbon or heteroatoms can be optionally substituted by one or more oxo or sulfido. In some embodiments, the heterocycloalkyl is a monocyclic 4-6 membered heterocycloalkyl having 1 or 2 heteroatoms independently selected from N, O, S, and B and having one or more oxidized ring members.

[0781] Examples of heterocycloalkyl groups include pyrrolidin-2-one, l,3-isoxazolidin-2-one, pyranyl. tetrahydropyran, oxetanyl, azetidinyl, morpholino, thiomorpholino, piperazinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, pyrrolidinyl, isoxazolidinyl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0782] isothiazolidinyl, pyrazolidinyl. oxazolidinyl, thiazolidinyl, imidazolidinyl, azepanyl, benzazapene, 1,2,3,4-tetrahydroisoquinoline, azabicyclo[3.1.0]hexanyl, diazabicyclo[3.1.0]hexanyl, oxabicyclo[2.1.1]hexanyl, azabicyclo[2.2.1]heptanyl, azabicyclo[2.2.1]heptan-7-yl, azabicyclo[2.2.1]heptan-2-yl, diazabicyclo[2.2.1]heptanyl, azabicyclo[3.1. l]heptanyl, diazabicyclo[3.1.1]heptanyl, azabicyclo[3.2. l]octanyl, diazabicyclo[3.2. l]octanyl, oxabicyclo[2.2.2]octanyl. azabicyclo[2.2.2]octanyl, azaadamantanyl, diazaadamantanyl, oxa-adamantanyl, azaspiro[3.3]heptanyl, diazaspiro[3.3]heptanyl, oxa-azaspiro[3.3]heptanyl, azaspiro[3.4]octanyl, diazaspiro[3.4]octanyl, oxa-azaspiro[3.4]octanyl, azaspiro[2.5]octanyl, diazaspiro[2.5]octanyl. azaspiro[4.4]nonanyl, diazaspiro[4.4]nonanyl, oxa-azaspiro[4.4]nonanyl, azaspiro[4.5]decanyl, diazaspiro[4.5]decanyl, diazaspiro[4.4]nonanyl, oxa-diazaspiro[4.4]nonanyl, and the like.

[0783] As used herein, “Co-Pcycloalkyl-Cn-m alkyl-’' refers to a group of formula cycloalkylalkylene-, wherein the cycloalkyl has o to p carbon atoms and the alkylene linking group has n to m carbon atoms.

[0784] As used herein, (R1A)m-C3-10 cycloalkyl-Ci-4 alk l refers to a group of formula cycloalkyl-alkylene-, wherein the cycloalkyl has 3-10 carbon atoms and the alkylene linking group has 1-4 carbon atoms, wherein the cycloalkyl ring is substituted by m independently selected R1Asubstituents.

[0785] As used herein, (Cs-io cycloalkyl)-(R1A1)m-Ci-4 alkyl refers to a group of formula cycloalkyl-alkylene-, wherein the cycloalkyl has 3-10 carbon atoms and the alkylene linking group has 1 -4 carbon atoms, wherein the alkylene linker is substituted by m independently- selected R1A1substituents.

[0786] As used herein ”Co-Paryl-Cn-m alkyl-” refers to a group of formula aryl-alkylene-, wherein the aryl has 0 to p carbon ring members and the alkylene linking group has n to m carbon atoms.

[0787] As used herein, “heteroaryl-Cn-malky l-” refers to a group of formula heteroarylalkylene-, wherein alkylene linking group has n to m carbon atoms.

[0788] As used herein “heterocycloalkyl-Cn-m alkyl-” refers to a group of formula heterocycloalkyl-alkylene-, wherein alkylene linking group has n to m carbon atoms.

[0789] As used herein, the term “alkylene” refers a divalent straight chain or branched alkyl linking group. Examples of “alkylene groups” include methylene, ethan-1,1-diyl, ethan-1,2-diyl, propan- 1,3-dilyl, propan- 1,2-diyl, propan- 1,1-diyl and the like.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0790] As used herein, the term "alkenylene" refers a divalent straight chain or branched alkenyl linking group. Examples of '‘alkenylene groups” include ethen- 1,1 -diyl, ethen-1,2-diyl, propen- 1,3-diyl, 2-buten-l,4-diyl, 3-penten-l,5-diyl, 3-hexen-1,6-diyl, 3-hexen-l,5-diyl, and the like.

[0791] As used herein, the term “alkynylene” refers a divalent straight chain or branched alkynyl linking group. Examples of “alkynylene groups” include propyn- 1,3-diyl, 2-butyn-1,4-diyl, 3-pentyn-l,5-diyl, 3-hexyn-l,6-diyl, 3-hexyn-l,5-diyl, and the like.

[0792] As used herein, an '‘alkyd linking group” is a bivalent straight chain or branched alkyl linking group (“alkylene group”). For example, “Co-Pcycloalkyl-Cn-m alkyl-”, “C0.paryl-Cn-m alkyl-”. “phenyl-Cn-m alkyl-”, “heteroaryl-Cn-malkyl-”, and “heterocycloalkyl-Cn-m alkyl-” contain alkyl linking groups. Examples of '‘alkyl linking groups” or “alkylene groups” include methylene, ethan- 1,1 -diyl, ethan-l,2-diyl, propan- 1,3-dilyl, propan- 1,2-diyl, propan-1,1 -diyl and the like.

[0793] As used herein, the term “oxo" refers to an oxygen atom (i.e., =0) as a divalent substituent, forming a carbonyl group when attached to a carbon (e.g., C=O or C(O)), or attached to a nitrogen or sulfur heteroatom forming a nitroso, sulfinyl or sulfonyl group.

[0794] As used herein, the term “independently selected from” means that each occurrence of a variable or substituent are independently selected at each occurrence from the applicable list.

[0795] At certain places, the definitions or embodiments refer to specific rings (e.g., an azetidine ring, a pyridine ring, etc.). Unless otherwise indicated, these rings can be attached to any ring member provided that the valency of the atom is not exceeded. For example, an azetidine ring may be attached at any position of the ring, whereas a pyridin-3-yl ring is attached at the 3-position.

[0796] The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present disclosure that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present disclosure areAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0797] described and may be isolated as a mixture of isomers or as separated isomeric forms. In some embodiments, the compound has the (R)-configuration. In some embodiments, the compound has the (S) -con figuration. The Formulas (e.g., Formula (I), (II), etc.) provided herein include stereoisomers of the compounds.

[0798] Resolution of racemic mixtures of compounds can be carried out by any of numerous methods known in the art. An example method includes fractional recrystallization using a chiral resolving acid which is an optically active, salt-forming organic acid. Suitable resolving agents for fractional recrystallization methods are, for example, optically active acids, such as the D and L forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid or the various optically active camphorsulfonic acids such as P-camphorsulfonic acid. Other resolving agents suitable for fractional cry stallization methods include stereoisomerically pure forms of a-methylbenzylamine (e.g., S and R forms, or diastereomerically pure forms), 2-phenylglycinol, norephedrine, ephedrine, N-methylephedrine, cyclohexylethylamine, 1,2-diaminocyclohexane, and the like.

[0799] Resolution of racemic mixtures can also be carried out by elution on a column packed with an optically active resolving agent (e.g., dinitrobenzoylphenylglycine). Suitable elution solvent composition can be determined by one skilled in the art.

[0800] Compounds provided herein also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone - enol pairs, amide- imidic acid pairs, lactam - lactim pairs, enamine - imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1H- and 3H-imidazole. 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H- isoindole, 2-hydroxypyridine and 2-pyridone, and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. It is intended that the claims to one tautomer cover both tautomers even if not specified.

[0801] All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g., hydrates and solvates) or can be isolated.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0802] In some embodiments, preparation of compounds can involve the addition of acids or bases to affect, for example, catalysis of a desired reaction or formation of salt forms such as acid addition salts.

[0803] In some embodiments, the compounds provided herein, or salts thereof, are substantially isolated. By "substantially isolated” is meant that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, for example, a composition enriched in the compounds provided herein. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%. at least about 97%, or at least about 99% by weight of the compounds provided herein, or salt thereof. Methods for isolating compounds and their salts are routine in the art.

[0804] The term “compound” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted. Compounds herein identified by name or structure as one particular tautomeric form are intended to include other tautomeric forms unless otherwise specified.

[0805] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0806] The present application also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the present disclosure include the conventional non-toxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present disclosure can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, non-aqueousAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0807] media like ether, ethyl acetate, alcohols (e.g., methanol, ethanol, iso-propanol, or butanol) or acetonitrile (ACN) are preferred. Lists of suitable salts are found in Remington 's Pharmaceutical Sciences, 17th ed.. Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977), each of which is incorporated herein by reference in its entirety.

[0808] Synthesis

[0809] As will be appreciated by those skilled in the art, the compounds provided herein, including salts and stereoisomers thereof, can be prepared using known organic synthesis techniques and can be synthesized according to any of numerous possible synthetic routes, such as those provided in the Schemes below.

[0810] The reactions for preparing compounds described herein can be carried out in suitable solvents which can be readily selected by one of skill in the art of organic synthesis. Suitable solvents can be substantially non-reactive with the starting materials (reactants), the intermediates or products at the temperatures at which the reactions are carried out, e.g., temperatures which can range from the solvent’s freezing temperature to the solvent’s boiling temperature. A given reaction can be carried out in one solvent or a mixture of more than one solvent. Depending on the particular reaction step, suitable solvents for a particular reaction step can be selected by the skilled artisan.

[0811] The expressions, '‘ambient temperature” or “room temperature” or “r.t.” as used herein, are understood in the art, and refer generally to a temperature, e.g., a reaction temperature, that is about the temperature of the room in which the reaction is carried out, for example, a temperature from about 20 °C to about 30 °C.

[0812] Preparation of compounds of the invention can involve the protection and deprotection of various chemical groups. The need for protection and deprotection, and the selection of appropriate protecting groups, can be readily determined by one skilled in the art. The chemistry of protecting groups is described, e.g., in Kocienski, Protecting Groups, (Thieme. 2007); Robertson, Protecting Group Chemistry. (Oxford University Press, 2000); Smith et al., March ’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6thEd. (Wiley, 2007); Peturssion et al., “Protecting Groups in Carbohydrate Chemistry,” J. Chem. Educ., 1997, 74(1 I ). 1297; and Wuts et al., Protective Groups in Organic Synthesis, 4th Ed., (Wiley, 2006).Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0813] Reactions can be monitored according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g.,1H or13C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), mass spectrometry or by chromatographic methods such as high performance liquid chromatography (HPLC), liquid chromatography -mass spectroscopy (LCMS). or thin layer chromatography (TLC). Compounds can be purified by those skilled in the art by a variety of methods, including high performance liquid chromatography (HPLC) and normal phase silica chromatography.

[0814] The Schemes below provide general guidance in connection with preparing the compounds of the invention. One skilled in the art would understand that the preparations shown in the Schemes can be modified or optimized using general knowledge of organic chemistry to prepare various compounds of the invention.

[0815] As will be appreciated by those skilled in the art, the compounds provided herein, including salts and stereoisomers thereof, can be prepared using known organic synthesis techniques and can be synthesized according to any of numerous possible synthetic routes.

[0816] Compounds of Formula (I) can be synthesized, for example, according to the process shown in Scheme 1. As depicted in Scheme 1, nucleophilic aromatic substitution reactions of compounds of Formula 1-1 (i.e., where Hal is a suitable halogen, such as Br or I) and amines of Formula 1-2 under appropriate conditions (e.g.. in the presence of a suitable base, such as NEt(z-Pr)2, in a suitable solvent, such as CH3CN) generates compounds of Formula 1-3.

[0817] Compounds of Formula 1-1 are commercially available, or can be synthesized, for example, by the process depicted in Scheme 2. Transition metal (e.g, Pd, Cu, Ni) catalyzed reactions (including, but not limited to, Suzuki, Stille. Negishi, or Ullman couplings) of compounds of Formula 1-3 and appropriate coupling partners of Formula 1-4 (e.g., heteroaryl boronic acids / esters, heteroaryl trialkyl tin, heteroaryl zinc reagents, or aromatic nitrogen heterocycles) affords compounds of Formula (I).

[0818] Scheme 1.

[0819] (R5)P

[0820] u U = B(OR)2, SnR3, ZnX H H (R3) 1-3 1-4 (I)

[0821]

[0822] Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0823] Compounds of Formula 1-1 can be synthesized, for example, according to the process shown in Scheme 2. As depicted in Scheme 2, reduction of compounds of Formula 2-1 using appropriate conditions (e.g., using a suitable reducing agent, such as NaBH4, in a suitable solvent sy stem, such as THF / EtOH) gives compound 2-2. Oxidation of 2-2 under appropriate conditions (e.g., using a suitable oxidant, such as Mn02, in a suitable solvent, such as CH2CI2) affords compounds of Formula 1-1.

[0824] Scheme 2.

[0825] Hal Hal Reduction Oxidation

[0826]

[0827] Compounds of Formula (I) can be prepared, for example, using the process shown in Scheme 3. In the process depicted in Scheme 3, borylation of compounds of Formula 1-3 under appropriate conditions (e.g., using a borylating reagent, such as bis(pinacolato)diboron, in the presence of a suitable catalyst, such as Pd(dppf)C12, and a base, such as KO Ac, in an appropriate solvent, such as 1,4-dioxane) affords compounds of Formula 3-1. Transition metal (e.g., Pd, Cu, Ni) catalyzed reactions (including, but not limited to, Suzuki or Chan-Lam couplings) of compounds of Formula 3-1 and appropriate coupling partners of Formula 3-2 (i.e., where V is a suitable group, such as a halogen, triflate, or hydrogen) using suitable conditions (e.g., using a suitable catalyst, such as XPhos Pd G2, and a base, such as CS2CO3, in an appropriate solvent, such as l,4-dioxane / H2O) affords compounds of Formula (I).

[0828] Scheme 3.

[0829] Borylation

[0830] V = Hal, OSO2CF3, H 3-1 3-2 (I)

[0831]

[0832] Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0833] Compounds of Formula 4-3 can be prepared, for example, using the process illustrated in Scheme 4. In the process depicted in Scheme 4, halogenation of compounds of Formula 4-1 under appropriate conditions (e.g., via reaction with a halogenating reagent, such as N-iodosuccinimide. in an appropriate solvent, such as 1,2-dichloroethane / AcOH) furnishes compounds of Formula 4-2 (e.g., where Hal is a suitable halogen, such as Cl, Br, or I).

[0834] Transition metal (e.g, Pd, Cu, Ni) catalyzed reactions (including, but not limited to, Buchwald, Ullman, Suzuki, Stille, orNegishi couplings) of compounds of Formula 4-2 and appropriate coupling partners (e.g., primary or secondary amines, aromatic nitrogen heterocycles, boronic acids / esters, trialkyl tin, or zinc reagents) affords compounds of Formula 4-3. In certain cases, Formula 4-3 is a version of Formula (I) where Y is O or S. and Z is CR1.

[0835]

[0836] Methods of Use

[0837] Compounds of the present disclosure (and pharmaceutically acceptable salts thereof) can inhibit CDK4 and therefore are useful for treating diseases wherein the underlying pathology is, wholly or partially, mediated by CDK4. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, inhibit CDK4. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK4 over CDK1, CDK6, and / or CDK7. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK4 over CDK1. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK4 over CDK7. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK4 over CDK6. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK4 over CDK6. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, are selective for CDK4 over CDK6. In some embodimetns, the selectivity referenced in each of theAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0838] embodiments of this paragraph is at least 2-fold, at least 3-fold, at least 5-fold, or at least 10-fold.

[0839] In some embodiments, the disclosure includes a method of treating a disease or disorder associated with CDK4 in a patient, comprising administering to the patient a therapeutically effective amount of the compound described herein, or pharmaceutically acceptable salt thereof. In some embodiments, the disclosure includes a method of treating a disease or disorder associated with CDK4 and / or CDK2 in a patient, comprising administering to the patient a therapeutically effective amount of the compound described herein, or pharmaceutically acceptable salt thereof. In some embodiments, the disclosure includes a method of treating a disease or disorder associated with CDK4 and CDK2 in a patient, comprising administering to the patient a therapeutically effective amount of the compound described herein, or pharmaceutically acceptable salt thereof.

[0840] Such diseases include cancer and other diseases with proliferation disorder. In some embodiments, the present disclosure provides treatment of an individual or a patient in vivo using a compound of Formula (1) or a salt thereof such that growth of cancerous tumors is inhibited. A compound of Formula (I) or of any of the formulas as described herein, or a compound as recited in any of the claims and described herein, or a salt thereof, can be used to inhibit the growth of cancerous tumors with aberrations that activate the CDK4 kinase and / or CDK2 activity. These include, but are not limited to. disease (e.g.. cancers) that are characterized by amplification or overexpression of CCNE1 such as ovarian cancer, uterine carcinosarcoma and breast cancer and p27 inactivation such as breast cancer and melanomas. Accordingly, in some embodiments of the methods, the patient has been previously determined to have an amplification of the cyclin El (CCNE1) gene and / or an expression level of CCNE1 in a biological sample obtained from the human subject that is higher than a control expression level of CCNE1. Alternatively, a compound of Formula (I) or of any of the formulas as described herein, or a compound as recited in any of the claims and described herein, or a salt thereof, can be used in conjunction with other agents or standard cancer treatments, as described below. In one embodiment, the present disclosure provides a method for inhibiting grow th of tumor cells in vitro. The method includes contacting the tumor cells in vitro with a compound of Formula (I) or of any of the formulas as described herein, or of a compound as recited in any of the claims and described herein, or of a salt thereof. In another embodiment, the present disclosure provides a method for inhibiting growth of tumor cells with CCNE1 amplification and overexpression in an individual or a patient. The methodAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0841] includes administering to the individual or patient in need thereof a therapeutically effective amount of a compound of Formula (I) or of any of the formulas as described herein, or of a compound as recited in any of the claims and described herein, or a salt or a stereoisomer thereof.

[0842] In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, inhibit CDK2 and / or CDK.4. In some embodiments, the compounds, and pharmaceutically acceptable salts thereof, inhibit CDK2 and CDK4. CDK2 is of particular interest because deregulation of CDK2 activity occurs frequently in a variety of human cancers. CDK2 plays a crucial role in promoting Gl / S transition and S phase progression. In complex with cyclin E (CCNE), CDK2 phosphorylates retinoblastoma pocket protein family members (p107, p130. pRb), leading to de-repression of E2F transcription factors, expression of Gl / S transition related genes and transition from G1 to S phase (Henley, S. A. and F. A. Dick, Cell Div, 2012, 7(1): p. 10). This in turn enables activation of CDK2 / cyclin A, which phosphorylates endogenous substrates that permit DNA synthesis, replication and centrosome duplication (Ekholm, S. V. and S. I. Reed, Curr Opin Cell Biol, 2000. 12(6): 676-84). It has been reported that the CDK2 pathway influences tumorigenesis mainly through amplification and / or overexpression of CCNE1 and mutations that inactivate CDK2 endogenous inhibitors (e.g., p27), respectively (Xu. X., et al., Biochemistry, 1999. 38(27): 8713-22).

[0843] CCNE1 copy -number gain and overexpression have been identified in ovarian, gastric, endometrial, breast and other cancers and been associated with poor outcomes in these tumors (Keyomarsi, K., et al., N Engl J Med, 2002. 347(20): 1566-75; Nakayama, N., et al., Cancer, 2010. 116(11): 2621-34; Au-Yeung, G., et al., Clin Cancer Res, 2017. 23(7): 1862-1874; Rosen. D. G., et al., Cancer, 2006. 106(9): 1925-32). Amplification and / or overexpression of CCNE1 also reportedly contribute to trastuzumab resistance in HER2+ breast cancer and resistance to CDK4 / 6 inhibitors in estrogen receptor-positive breast cancer (Scaltriti, M., et al., Proc Natl Acad Sci USA, 2011. 108(9): 3761-6; Herrera- Abreu, M. T., et al., Cancer Res, 2016. 76(8): 2301-13). Various approaches targeting CDK2 have been shown to induce cell cycle arrest and tumor growth inhibition (Chen, Y. N., et al., Proc Natl Acad Sci USA, 1999. 96(8): 4325-9; Mendoza, N„ et al.. Cancer Res, 2003. 63(5): 1020-4). Inhibition of CDK2 also reportedly restores sensitivity to trastuzumab treatment in resistant HER2+ breast tumors in a preclinical model (Scaltriti, supra).

[0844] In some embodiments, provided herein is a method of inhibiting CDK4, comprising contacting the CDK4 with a compound of Formula (I) or any of the formulas as describedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0845] herein, a compound as recited in any of the claims and described herein, or a salt thereof. In some embodiments, provided herein is a method of inhibiting CDK4 in a patient, comprising administering to the patient a compound of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or a salt thereof.

[0846] In some embodiments, provided herein is a method of inhibiting CDK4 and / or CDK2, comprising contacting the CDK4 and / or CDK2 with a compound of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or a salt thereof. In some embodiments, provided herein is a method of inhibiting CDK4 and / or CDK2 in a patient, comprising administering to the patient a compound of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or a salt thereof.

[0847] In some embodiments, provided herein is a method of inhibiting CDK4 and CDK2, comprising contacting the CDK4 and CDK2 with a compound of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or a salt thereof. In some embodiments, provided herein is a method of inhibiting CDK4 and CDK2 in a patient, comprising administering to the patient a compound of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or a salt thereof.

[0848] In some embodiments, provided herein is a method for treating cancer. The method includes administering to a patient (in need thereof), a therapeutically effective amount of a compound of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or a salt thereof. In another embodiment, the cancer is characterized by amplification or overexpression of CCNE1. In some embodiments, the cancer is ovarian cancer or breast cancer, characterized by amplification or overexpression of CCNE1.

[0849] In some embodiments, provided herein is a method of treating a disease or disorder associated with CDK4 (or alternatively, CDK4 and / or CDK2, or alternatively, CDK4 and CDK2) in a patient, comprising administering to the patient a therapeutically effective amount of a compound of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or a salt thereof. In some embodiments, the disease or disorder associated w ith CDK4 (or alternatively, CDK4 and / or CDK2, or alternatively, CDK4 and CDK2) is associated with an amplification of the cyclin El (CCNE1) gene and / or overexpression of CCNE1.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0850] In some embodiments, the disease or disorder treatable by the compounds and salts described herein is N-myc amplified neuroblastoma cells (see Molenaar, et al.. Proc Natl Acad Sci USA 106(31): 12968-12973) K-Ras mutant lung cancers (see Hu, S., et al., Mol Cancer Ther, 2015. 14(11): 2576-85, and cancers with FBW7 mutation and CCNE1 overexpression (see Takada et al., Cancer Res, 2017. 77(18): 4881-4893).

[0851] In some embodiments, the disease or disorder treatable by the compounds and salts described herein is lung squamous cell carcinoma, lung adenocarcinoma, pancreatic adenocarcinoma, breast invasive carcinoma, uterine carcinosarcoma, ovarian serous cystadenocarcinoma, stomach adenocarcinoma, esophageal carcinoma, bladder urothelial carcinoma, mesothelioma, or sarcoma.

[0852] In some embodiments, the disease or disorder treatable by the compounds and salts described herein is lung adenocarcinoma, breast invasive carcinoma, uterine carcinosarcoma, ovarian serous cystadenocarcinoma, or stomach adenocarcinoma.

[0853] In some embodiments, the disease or disorder treatable by the compounds and salts described herein is an adenocarcinoma, carcinoma, or cystadenocarcinoma.

[0854] In some embodiments, the disease or disorder treatable by the compounds and salts described herein is uterine cancer, ovarian cancer, stomach cancer, esophageal cancer, lung cancer, bladder cancer, pancreatic cancer, or breast cancer.

[0855] In some embodiments, the disease or disorder treatable by the compounds and salts described herein is a cancer.

[0856] In some embodiments, the cancer is characterized by amplification or overexpression of CCNE1. In some embodiments, the cancer is ovarian cancer or breast cancer, characterized by amplification or overexpression of CCNE1.

[0857] In some embodiments, the breast cancer is chemotherapy or radiotherapy resistant breast cancer, endocrine resistant breast cancer, trastuzumab resistant breast cancer, or breast cancer demonstrating primary' or acquired resistance to CDK4 / 6 inhibition. In some embodiments, the breast cancer is advanced or metastatic breast cancer.

[0858] Examples of cancers that are treatable using the compounds of the present disclosure include, but are not limited to, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, uterine cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, endometrial cancer, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin’s Disease, non-Hodgkin’s lymphoma,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0859] cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, sarcoma of soft tissue, cancer of the urethra, cancer of the penis, chronic or acute leukemias including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, solid tumors of childhood, lymphocytic lymphoma, cancer of the bladder, cancer of the kidney or urethra, carcinoma of the renal pelvis, neoplasm of the central nervous system (CNS), primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi’s sarcoma, epidermoid cancer, squamous cell cancer, T-cell lymphoma, environmentally induced cancers including those induced by asbestos, and combinations of said cancers. The compounds of the present disclosure are also useful for the treatment of metastatic cancers.

[0860] In some embodiments, cancers treatable with compounds of the present disclosure include melanoma (e.g., metastatic malignant melanoma, BRAF and HSP90 inhibition-resistant melanoma), renal cancer (e.g., clear cell carcinoma), prostate cancer (e.g., hormone refractory prostate adenocarcinoma), breast cancer, colon cancer, lung cancer (e.g., non-small cell lung cancer and small cell lung cancer), squamous cell head and neck cancer, urothelial cancer (e.g., bladder) and cancers with high microsatellite instability (MSIhlgh). Additionally, the disclosure includes refractory or recurrent malignancies whose growth may be inhibited using the compounds of the disclosure.

[0861] In some embodiments, cancers that are treatable using the compounds of the present disclosure include, but are not limited to, solid tumors (e.g., prostate cancer, colon cancer, esophageal cancer, endometrial cancer, ovarian cancer, uterine cancer, renal cancer, hepatic cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, cancers of the head and neck, thyroid cancer, glioblastoma, sarcoma, bladder cancer, etc.), hematological cancers (e.g.. lymphoma, leukemia such as acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), DLBCL, mantle cell lymphoma, Non-Hodgkin lymphoma (including follicular lymphoma, including relapsed or refractory NHL and recurrent follicular), Hodgkin lymphoma or multiple myeloma) and combinations of said cancers.

[0862] In some embodiments, cancers that are treatable using the compounds of the present disclosure include, but are not limited to, cholangiocarcinoma, bile duct cancer, triple negative breast cancer, rhabdomyosarcoma, small cell lung cancer, leiomyosarcoma, hepatocellular carcinoma, Ewing’s sarcoma, brain cancer, brain tumor, astrocytoma, neuroblastoma,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0863] neurofibroma, basal cell carcinoma, chondrosarcoma, epithelioid sarcoma, eye cancer, Fallopian tube cancer, gastrointestinal cancer, gastrointestinal stromal tumors, hairy cell leukemia, intestinal cancer, islet cell cancer, oral cancer, mouth cancer, throat cancer, laryngeal cancer, lip cancer, mesothelioma, neck cancer, nasal cavity' cancer, ocular cancer, ocular melanoma, pelvic cancer, rectal cancer, renal cell carcinoma, salivary gland cancer, sinus cancer, spinal cancer, tongue cancer, tubular carcinoma, urethral cancer, and ureteral cancer.

[0864] In some embodiments, the compounds of the present disclosure can be used to treat sickle cell disease and sickle cell anemia.

[0865] In some embodiments, diseases and indications that are treatable using the compounds of the present disclosure include, but are not limited to hematological cancers, sarcomas, lung cancers, gastrointestinal cancers, genitourinary tract cancers, liver cancers, bone cancers, nervous system cancers, gynecological cancers, and skin cancers.

[0866] Exemplary' hematological cancers include lymphomas and leukemias such as acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, Non-Hodgkin lymphoma (including relapsed or refractory NHL and recurrent follicular), Hodgkin lymphoma, myeloproliferative diseases (e.g., primary myelofibrosis (PMF), polycythemia vera (PV), and essential thrombocytosis (ET), myelodysplasia syndrome (MDS). T-cell acute lymphoblastic lymphoma (T-ALL) and multiple myeloma (MM).

[0867] Exemplary sarcomas include chondrosarcoma, Ewing’s sarcoma, osteosarcoma, rhabdomyosarcoma, angiosarcoma, fibrosarcoma, liposarcoma, myxoma, rhabdomyoma, rhabdosarcoma, fibroma, lipoma, harmatoma, and teratoma.

[0868] Exemplary lung cancers include non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), bronchogenic carcinoma, squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma, alveolar (bronchiolar) carcinoma, bronchial adenoma, chondromatous hamartoma, and mesothelioma.

[0869] Exemplary gastrointestinal cancers include cancers of the esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors, vipoma), small bowel (adenocarcinoma, lymphoma, carcinoid tumors, Kaposi’s sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large bowelAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0870] (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma), and colorectal cancer.

[0871] Exemplary genitourinary tract cancers include cancers of the kidney (adenocarcinoma, Wilm's tumor [nephroblastoma]), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), and testis (seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumors, lipoma).

[0872] Exemplary liver cancers include hepatoma (hepatocellular carcinoma), cholangiocarcinoma. hepatoblastoma, angiosarcoma, hepatocellular adenoma, and hemangioma.

[0873] Exemplary bone cancers include, for example, osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing’s sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochrondroma (osteocartilaginous exostoses), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma, and giant cell tumors.

[0874] Exemplary nervous system cancers include cancers of the skull (osteoma, hemangioma, granuloma, xanthoma, osteitis deformans), meninges (meningioma, meningiosarcoma, gliomatosis), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germinoma (pinealoma), glioblastoma, glioblastoma multiform, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors), and spinal cord (neurofibroma, meningioma, glioma, sarcoma), as well as neuroblastoma and Lhermitte-Duclos disease.

[0875] Exemplary gynecological cancers include cancers of the uterus (endometrial carcinoma), cervix (cervical carcinoma, pre -tumor cervical dysplasia), ovaries (ovarian carcinoma (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa-thecal cell tumors, Sertoli-Leydig cell tumors, dysgerminoma, malignant teratoma), vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma), and fallopian tubes (carcinoma).

[0876] Exemplary skin cancers include melanoma, basal cell carcinoma, Merkel cell carcinoma, squamous cell carcinoma, Kaposi’s sarcoma, moles dysplastic nevi, lipoma, angioma, dermatofibroma, and keloids. In some embodiments, diseases and indications thatAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0877] are treatable using the compounds of the present disclosure include, but are not limited to, sickle cell disease (e.g., sickle cell anemia), triple-negative breast cancer (TNBC), myelodysplastic syndromes, testicular cancer, bile duct cancer, esophageal cancer, and urothelial carcinoma.

[0878] In some embodiments, the cancer is ovarian cancer, breast cancer, or endometrial cancer.

[0879] In some embodiments, the cancer is ovarian cancer.

[0880] In some embodiments, the cancer is breast cancer.

[0881] In some embodiments, the cancer is endometrial cancer.

[0882] In some embodiments, the cancer is selected from breast cancer, ovarian cancer, a gynecological cancer, a gastrointestinal cancer, prostate cancer, melanoma, colorectal cancer, endometrial cancer, esophageal cancer, gastric cancer, liposarcoma, Ewing sarcoma, or melanoma.

[0883] In some embodiments, the cancer is platinum resistant.

[0884] In some embodiments, the cancer is platinum sensitive.

[0885] In some embodiments, the cancer is breast cancer which is hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-).

[0886] It is believed that compounds of Formula (I), or any of the embodiments thereof, may possess satisfactory pharmacological profile and promising biopharmaceutical properties, such as toxicological profile, metabolism and pharmacokinetic properties, solubility, and permeability. It will be understood that determination of appropriate biopharmaceutical properties is within the know ledge of a person skilled in the art, e.g., determination of cytotoxicity’ in cells or inhibition of certain targets or channels to determine potential toxicity’.

[0887] The terms “individual”, “patient,” and “subject” used interchangeably, refer to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans.

[0888] The phrase “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinician.

[0889] As used herein, the term “treating” or “treatment” refers to one or more of (1) inhibiting the disease; e.g.. inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition orAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0890] disorder (i.e.. arresting further development of the pathology and / or symptomatology); and (2) ameliorating the disease; e.g., ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and / or symptomatology ) such as decreasing the severity of disease.

[0891] In some embodiments, the compounds of the invention are useful in preventing or reducing the risk of developing any of the diseases referred to herein; e g., preventing or reducing the risk of developing a disease, condition or disorder in an individual who may be predisposed to the disease, condition or disorder but does not yet experience or display the pathology or symptomatology of the disease.

[0892] Combination Therapies

[0893] I. Cancer therapies

[0894] Cancer cell growth and survival can be impacted by dysfunction in multiple signaling pathways. Thus, it is useful to combine different enzyme / protein / receptor inhibitors, exhibiting different preferences in the targets which they modulate the activities of, to treat such conditions. Targeting more than one signaling pathway (or more than one biological molecule involved in a given signaling pathway) may reduce the likelihood of drug-resistance arising in a cell population, and / or reduce the toxicity of treatment.

[0895] One or more additional pharmaceutical agents such as, for example, chemotherapeutics, anti-inflammatory agents, steroids, immunosuppressants, immune-oncology agents, metabolic enzyme inhibitors, chemokine receptor inhibitors, and phosphatase inhibitors, as well as targeted therapies such as Bcr-Abl, Flt-3, EGFR, HER2, JAK. c-MET, VEGFR, PDGFR. c-Kit, 1GF-1R. RAF. FAK, and CDK4 / 6 kinase inhibitors such as, for example, those described in WO 2006 / 056399 can be used in combination with the compounds of the present disclosure for treatment of CDK4 -associated diseases, disorders or conditions. Other agents such as therapeutic antibodies can be used in combination with the compounds of the present disclosure for treatment of CDK4 -associated diseases, disorders or conditions. The one or more additional pharmaceutical agents can be administered to a patient simultaneously or sequentially.

[0896] In some embodiments, the one or more additional pharmaceutical agents is an aromatase inhibitor, luteinizing hormone-rel easing hormone (LHRH) agonist, an antiandrogen, therapy targeting the PI3K / AKT / mTOR (PAM) pathway, a selective estrogenAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0897] receptor degrader (SERD). a CDK2 inhibitor, a CDK4 / 6 inhibitor, a CDK4 inhibitor, or VEGF-A inhibitor, or a combination thereof.

[0898] In some embodiments, the one or more additional pharmaceutical agents is a CDK2 inhibitor which is selected from 8-ethoxy-N-((3R,4S)-3-methyl-l-(methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)-[l,2,4]triazolo[l,5-a]pyridin-2 -amine; N-((3R,4S)-1-(cyclopropylsulfonyl)-3-methylpiperidin-4-yl)-8-ethoxy-7-(lH-pyrazol-4-yl)- [1.2.4]triazolo[l,5-a]pyridin-2-amine; 8-isopropoxy-N-((3R,4S)-3-methyl-l-(methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)-[l,2,4]triazolo[l,5-c]pyrimidin-2-amine; 8-(ethoxy-d5)-N-((3R,4S)-3-methyl-l-(methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)- [1.2.4]triazolo[1.5-a]pyridin-2-amine; or 8-isopropoxy-N-((3R,4S)-3-methyl-l-(methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)-[l,2,4]triazolo[l,5-a]pyridin-2-amine; or a pharmaceutically acceptable salt thereof.

[0899] In some embodiments, the one or more pharmaceutical agents is:

[0900] a VEGF-A inhibitor, which is bevacizumab; or

[0901] a PAM therapy, which is alpelisib, capivasertib, or everolimus, or a pharmaceutically acceptable salt thereof; or

[0902] a SERD, which is is fluvestrant, camizestrant, amcenestrant, elacestrant, giredestrant, imlunestrant, rintodestrant, AZD9496, borestrant, taragarestrant, or ZN-c5, or a pharmaceutically acceptable salt thereof; or

[0903] aCDK4 / 6 inhibitor, which is albociclib, ribociclib, albociclib, abemaciclib, or dalpiciclib, or a pharmaceutically acceptable salt thereof; or

[0904] a CDK4 inhibitor, which is atirmociclib, or a pharmaceutically acceptable salt thereof; or

[0905] a CDK2 inhibitor, which is ebvaciclib, or a pharmaceutically acceptable salt thereof; or

[0906] an aromatase inhibitor, which is anastrozole, exemestane, letrozole, vorozole, formestane, or fadrozole, or a pharmaceutically acceptable salt thereof; or

[0907] a LHRH agonist, which is leuprolide, goserelin, triptorelin, histrelin, or buserelin, or a pharmaceutically acceptable salt thereof; or

[0908] an anti-androgen, which is spironolactone, finasteride, dutasteride, bicalutamide, flutamide, enzalutamide, apalutamide, cyproterone, abiraterone, chlormadinone, clascoterone, megestrol, nilutamide, or darolutamide, or a pharmaceutically acceptable salt thereof.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0909] In some embodiments, the compound or salt is administered or used in combination with a BCL2 inhibitor.

[0910] The compounds as disclosed herein can be used in combination with one or more other enzyme / protein / receptor inhibitors therapies for the treatment of diseases, such as cancer and other diseases or disorders described herein. Examples of diseases and indications treatable with combination therapies include those as described herein. Examples of cancers include solid tumors and non-solid tumors, such as liquid tumors, and blood cancers.

[0911] Examples of infections include viral infections, bacterial infections, fungus infections or parasite infections. For example, the compounds of the present disclosure can be combined with one or more inhibitors of the following kinases for the treatment of cancer: Aktl, Akt2, Akt3, BCL2, CDK4 / 6, TGF-βR, PKA, PKG, PKC, CaM-kinase, phosphorylase kinase, MEKK, ERK, MAPK, mTOR, EGFR, HER2, HER3, HER4, INS-R, IDH2, IGF-1R, IR-R, PDGFaR, PDGFpR, PI3K (alpha, beta, gamma, delta, and multiple or selective). CSF1R, KIT, FLK-II, KDR / FLK-1, FLK-4, flt-1, FGFR1, FGFR2, FGFR3, FGFR4, c-Met, PARP, Ron, Sea, TRKA, TRKB, TRKC, TAM kinases (Axl, Mer, Tyro3), FLT3, VEGFR / Flt2, Flt4, EphAl, EphA2, EphA3, EphB2, EphB4, Tie2, Src, Fyn, Lek, Fgr, Btk, Fak, SYK, FRK, JAK, ABL, ALK and B-Raf. In some embodiments, the compounds of the present disclosure can be combined with one or more of the following inhibitors for the treatment of cancer or infections. Non-limiting examples of inhibitors that can be combined with the compounds of the present disclosure for treatment of cancer and infections include an FGFR inhibitor (FGFR1, FGFR2, FGFR3 orFGFR4, e.g., pemigatinib (INCB54828), INCB62079), an EGFR inhibitor (also known as ErB-1 or HER-1; e.g.. erlotinib, gefitinib. vandetanib, orsimertinib, cetuximab, necitumumab, or panitumumab), a VEGFR inhibitor or pathw ay blocker (e.g. bevacizumab, pazopanib, sunitinib, sorafenib, axitinib, regorafenib, ponatinib, cabozantinib, vandetanib, ramucirumab, lenvatinib, ziv-aflibercept), a PARP inhibitor (e.g., olaparib, rucaparib, veliparib or niraparib), a JAK inhibitor (JAK1 and / or JAK2, e.g., ruxolitinib or baricitinib; JAK1, e.g., itacitinib (INCB39110), INCB052793, or INCB054707), an IDO inhibitor (e.g., epacadostat, NLG919, or BMS-986205, MK7162), an LSD1 inhibitor (e.g., GSK2979552, INCB59872 and INCB60003), a TDO inhibitor, a PI3K-delta inhibitor (e.g., parsaclisib (INCB50465) or INCB50797), a PI3K-gamma inhibitor such as PI3K-gamma selective inhibitor, a Pirn inhibitor (e.g., INCB53914), a CSF1R inhibitor, a TAM receptor tyrosine kinases (Tyro-3, Axl, and Mer; e.g., INCB081776), an adenosine receptor antagonist (e.g., A2a / A2b receptor antagonist), an HPK1 inhibitor, a chemokineAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0912] receptor inhibitor (e.g., CCR2 or CCR5 inhibitor), a SHP1 / 2 phosphatase inhibitor, a histone deacetylase inhibitor (HD AC) such as an HD AC 8 inhibitor, an angiogenesis inhibitor, an interleukin receptor inhibitor, bromo and extra terminal family members inhibitors (for example, bromodomain inhibitors or BET inhibitors such as INCB54329 and INCB57643), c-MET inhibitors (e.g., capmatinib), an anti-CD19 antibody (e.g., tafasitamab), an ALK2 inhibitor (e.g., INCB00928); or combinations thereof.

[0913] In some embodiments, the compound or salt described herein is administered with a PI3KS inhibitor. In some embodiments, the compound or salt described herein is administered with a JAK inhibitor. In some embodiments, the compound or salt described herein is administered with a JAK1 or JAK2 inhibitor (e.g., baricitinib or ruxolitinib). In some embodiments, the compound or salt described herein is administered with a JAK1 inhibitor. In some embodiments, the compound or salt described herein is administered with a JAK1 inhibitor, which is selective over JAK2.

[0914] Example antibodies for use in combination therapy include, but are not limited to, trastuzumab (e.g., anti-HER2), ranibizumab (e.g., anti-VEGF-A), bevacizumab (AVASTINTM, e.g., anti-VEGF), panitumumab (e.g., anti-EGFR), cetuximab (e.g., anti-EGFR), rituxan (e.g., anti-CD20), and antibodies directed to c-MET.

[0915] One or more of the following agents may be used in combination with the compounds of the present disclosure and are presented as a non-limiting list: a cytostatic agent, cisplatin, doxorubicin, taxotere, taxol, etoposide, irinotecan, camptosar, topotecan, paclitaxel, docetaxel, epothilones, tamoxifen, 5 -fluorouracil, methotrexate, temozolomide, cyclophosphamide, SCH 66336, R115777, L778,123, BMS 214662, IRESSA™(gefitinib), TARCEVA™ (erlotinib), antibodies to EGFR, intron. ara-C, adriamycin. cytoxan, gemcitabine, uracil mustard, chlormethine, ifosfamide, melphalan, chlorambucil, pipobroman, triethylenemelamine, triethylenethiophosphoramine, busulfan, carmustine, lomustine, streptozocin, dacarbazine, floxuridine, cytarabine, 6-mercaptopurine, 6-thioguanine, fludarabine phosphate, oxaliplatin, leucovirin, ELOXATIN™ (oxaliplatin), pentostatine, vinblastine, vincristine, vindesine, bleomycin, dactinomycin, daunorubicin. doxorubicin, epirubicin, idarubicin, mithramycin, deoxy coformycin, mitomycin-C, L-asparaginase, teniposide, 17-alpha-ethinylestradiol, diethylstilbestrol, testosterone, prednisone, fluoxymesterone, dromostanolone propionate, testolactone, megestrolacetate, methylprednisolone, methyltestosterone, prednisolone, triamcinolone, chlorotrianisene, hydroxy progesterone, aminoglutethimide, estramustine, medroxyprogesterone acetate.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0916] leuprolide, flutamide, toremifene, goserelin, carboplatin, hydroxyurea, amsacrine, procarbazine, mitotane, mitoxantrone, levamisole, navelbene, anastrazole, letrazole, capecitabine, reloxafine, droloxafine, hexamethyl melamine, avastin, HERCEPTIN™ (trastuzumab), BEXXAR™ (tositumomab), VELCADE™ (bortezomib), ZEVALIN™ (ibritumomab tiuxetan), TRISENOX™ (arsenic trioxide), XELODA™ (capecitabine), vinorelbine, porfimer, ERBITUX™ (cetuximab), thiotepa, altretamine. melphalan. trastuzumab, lerozole, fulvestrant, exemestane, ifosfomide, rituximab, C225 (cetuximab). Campath (alemtuzumab), clofarabine, cladribine, aphidicolon, rituxan, sunitinib, dasatinib, tezacitabine, Smll, fludarabine, pentostatin, triapine, didox, trimidox, amidox, 3-AP, and MDL-101,731.

[0917] The compounds of the present disclosure can further be used in combination with other methods of treating cancers, for example by chemotherapy, irradiation therapy, tumor-targeted therapy, adjuvant therapy, immunotherapy or surgery.. Examples of immunotherapy include cytokine treatment (e.g., interferons, GM-CSF, G-CSF, IL-2), CRS-207 immunotherapy, cancer vaccine, monoclonal antibody, bispecific or multi-specific antibody, antibody drug conjugate, adoptive T cell transfer, Toll receptor agonists, RIG-I agonists, oncolytic virotherapy and immunomodulating small molecules, including thalidomide or JAK1 / 2 inhibitor, PI3K5 inhibitor and the like. The compounds can be administered in combination with one or more anti-cancer drugs, such as a chemotherapeutic agent. Examples of chemotherapeutics include any of: abarelix, aldesleukin, alemtuzumab, alitretinoin, allopurinol, altretamine, anastrozole, arsenic trioxide, asparaginase, azacitidine, bevacizumab, bexarotene, baricitinib, bleomycin, bortezomib, busulfan intravenous, busulfan oral, calusterone, capecitabine, carboplatin, carmustine, cetuximab, chlorambucil, cisplatin, cladribine, clofarabine, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daltepann sodium, dasatinib, daunorubicin, decitabine, denileukin, denileukin diftitox, dexrazoxane, docetaxel, doxorubicin, dromostanolone propionate, eculizumab, epirubicin, erlotinib, estramustine, etoposide phosphate, etoposide, exemestane, fentanyl citrate, filgrastim, floxuridine, fludarabine, fluorouracil, fulvestrant, gefitinib, gemcitabine, gemtuzumab ozogamicin, goserelin acetate, histrelin acetate, ibritumomab tiuxetan, idarubicin, ifosfamide, imatinib mesylate, interferon alfa 2a, irinotecan, lapatinib ditosylate, lenalidomide, letrozole, leucovorin, leuprolide acetate, levamisole, lomustine, meclorethamine, megestrol acetate, melphalan, mercaptopurine, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone phenpropionate, nelarabine, nofetumomab, oxaliplatin, paclitaxel.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0918] pamidronate. panitumumab, pegaspargase, pegfilgrastim, pemetrexed disodium, pentostatin, pipobroman, plicamycin, procarbazine, quinacrine, rasburicase, rituximab, ruxolitinib, sorafenib, streptozocin, sunitinib, sunitinib maleate, tamoxifen, temozolomide, teniposide, testolactone, thalidomide, thioguanine, thiotepa, topotecan, toremifene, tositumomab, trastuzumab, tretinoin, uracil mustard, valrubicin, vinblastine, vincristine, vinorelbine, vorinostat, and zoledronate.

[0919] Additional examples of chemotherapeutics include proteasome inhibitors (e.g., bortezomib), thalidomide, revlimid, and DNA-damaging agents such as melphalan, doxorubicin, cyclophosphamide, vincristine, etoposide, carmustine, and the like.

[0920] Example steroids include corticosteroids such as dexamethasone or prednisone.

[0921] Example Bcr-Abl inhibitors include imatinib mesylate (GLEEVAC™), nilotinib, dasatinib, bosutinib, and ponatinib, and pharmaceutically acceptable salts. Other example suitable Bcr-Abl inhibitors include the compounds, and pharmaceutically acceptable salts thereof, of the genera and species disclosed in U. S. Pat. No. 5,521,184, WO 04 / 005281, and U. S. Ser. No. 60 / 578,491.

[0922] Example suitable Flt-3 inhibitors include midostaurin, lestaurtinib, linifanib, sunitinib, sunitinib, maleate, sorafenib, quizartinib, crenolanib, pacritinib, tandutinib, PLX3397 and ASP2215, and their pharmaceutically acceptable salts. Other example suitable Flt-3 inhibitors include compounds, and their pharmaceutically acceptable salts, as disclosed in WO 03 / 037347, WO 03 / 099771, and WO 04 / 046120.

[0923] Example suitable RAF inhibitors include dabrafenib, sorafenib, and vemurafenib, and their pharmaceutically acceptable salts. Other example suitable RAF inhibitors include compounds, and their pharmaceutically acceptable salts, as disclosed in WO 00 / 09495 and WO 05 / 028444.

[0924] Example suitable FAK inhibitors include VS-4718, VS-5095, VS-6062, VS-6063, BI853520, and GSK2256098, and their pharmaceutically acceptable salts. Other example suitable FAK inhibitors include compounds, and their pharmaceutically acceptable salts, as disclosed in WO 04 / 080980. WO 04 / 056786, WO 03 / 024967, WO 01 / 064655, WO 00 / 053595, and WO 01 / 014402.

[0925] Example suitable CDK4 / 6 inhibitors include palbociclib, ribociclib, trilaciclib, lerociclib, and abemaciclib, and their pharmaceutically acceptable salts. Other example suitable CDK4 / 6 inhibitors include compounds, and their pharmaceutically acceptable salts,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0926] as disclosed in WO 09 / 085185, WO 12 / 129344. WO 11 / 101409, WO 03 / 062236, WO 10 / 075074, and WO 12 / 061156.

[0927] In some embodiments, the compounds of the disclosure can be used in combination with one or more other kinase inhibitors including imatinib, particularly for treating patients resistant to imatinib or other kinase inhibitors.

[0928] In some embodiments, the compounds of the disclosure can be used in combination with a chemotherapeutic in the treatment of cancer, and may improve the treatment response as compared to the response to the chemotherapeutic agent alone, without exacerbation of its toxic effects. In some embodiments, the compounds of the disclosure can be used in combination with a chemotherapeutic provided herein. For example, additional pharmaceutical agents used in the treatment of multiple myeloma, can include, without limitation, melphalan, melphalan plus prednisone [MP], doxorubicin, dexamethasone, and Velcade (bortezomib). Further additional agents used in the treatment of multiple myeloma include Bcr-Abl, Flt-3. RAF and FAK kinase inhibitors. In some embodiments, the agent is an alkylating agent, a proteasome inhibitor, a corticosteroid, or an immunomodulatory agent. Examples of an alkylating agent include cyclophosphamide (CY), melphalan (MEL), and bendamustine. In some embodiments, the proteasome inhibitor is carfilzomib. In some embodiments, the corticosteroid is dexamethasone (DEX). In some embodiments, the immunomodulatory agent is lenalidomide (LEN) or pomalidomide (POM). Additive or synergistic effects are desirable outcomes of combining a compound or salt of the present disclosure with an additional agent.

[0929] The agents can be combined with the present compound in a single or continuous dosage form, or the agents can be administered simultaneously or sequentially as separate dosage forms.

[0930] The compounds of the present disclosure can be used in combination with one or more other inhibitors or one or more therapies for the treatment of infections. Examples of infections include viral infections, bacterial infections, fungus infections or parasite infections.

[0931] In some embodiments, a corticosteroid such as dexamethasone is administered to a patient in combination with the compounds of the disclosure where the dexamethasone is administered intermittently as opposed to continuously.

[0932] The compounds of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or salts thereof can beAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0933] combined with another immunogenic agent, such as cancerous cells, purified tumor antigens (including recombinant proteins, peptides, and carbohydrate molecules), cells, and cells transfected with genes encoding immune stimulating cytokines. Non-limiting examples of tumor vaccines that can be used include peptides of melanoma antigens, such as peptides of gplOO, MAGE antigens, Trp-2, MARTI and / or tyrosinase, or tumor cells transfected to express the cytokine GM-CSF.

[0934] The compounds of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or salts thereof can be used in combination with a vaccination protocol for the treatment of cancer. In some embodiments, the tumor cells are transduced to express GM-CSF. In some embodiments, tumor vaccines include the proteins from viruses implicated in human cancers such as Human Papilloma Viruses (HPV), Hepatitis Viruses (HBV and HCV) and Kaposi’s Herpes Sarcoma Virus (KHSV). In some embodiments, the compounds of the present disclosure can be used in combination with tumor specific antigen such as heat shock proteins isolated from tumor tissue itself. In some embodiments, the compounds of Formula (1) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or salts thereof can be combined with dendritic cells immunization to activate potent anti-tumor responses.

[0935] The compounds of the present disclosure can be used in combination with bispecific macrocyclic peptides that target Fe alpha or Fe gamma receptor-expressing effectors cells to tumor cells. The compounds of the present disclosure can also be combined with macrocyclic peptides that activate host immune responsiveness.

[0936] In some further embodiments, combinations of the compounds of the disclosure with other therapeutic agents can be administered to a patient prior to, during, and / or after a bone marrow transplant or stem cell transplant. The compounds of the present disclosure can be used in combination with bone marrow transplant for the treatment of a variety of tumors of hematopoietic origin.

[0937] The compounds of Formula (I) or any of the formulas as described herein, a compound as recited in any of the claims and described herein, or salts thereof can be used in combination with vaccines, to stimulate the immune response to pathogens, toxins, and self -antigens. Examples of pathogens for which this therapeutic approach may be particularly useful include pathogens for which there is currently no effective vaccine, or pathogens for which conventional vaccines are less than completely effective. These include, but are notAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0938] limited to, HIV, Hepatitis (A, B, & C), Influenza, Herpes. Giardia, Malaria, Leishmania, Staphylococcus aureus, Pseudomonas Aeruginosa.

[0939] Viruses causing infections treatable by methods of the present disclosure include, but are not limited to human papillomavirus, influenza, hepatitis A, B, C or D viruses, adenovirus, poxvirus, herpes simplex viruses, human cytomegalovirus, severe acute respiratory syndrome virus, Ebolavirus, measles virus, herpes virus (e.g., VZV, HSV-1, HAV-6, HSV-II, and CMV, Epstein Barr virus), flaviviruses, echovirus, rhinovirus, coxsackie virus, comovirus, respiratory syncytial virus, mumps virus, rotavirus, measles virus, rubella virus, parvovirus, vaccinia virus, HTLV virus, dengue virus, papillomavirus, molluscum virus, poliovirus, rabies virus, JC virus and arboviral encephalitis virus.

[0940] Pathogenic bacteria causing infections treatable by methods of the disclosure include, but are not limited to, chlamydia, rickettsial bacteria, mycobacteria, staphylococci, streptococci, pneumococci, meningococci and conococci, klebsiella, proteus, serratia, pseudomonas, legionella, diphtheria, salmonella, bacilli, cholera, tetanus, botulism, anthrax, plague, leptospirosis, and Lyme’s disease bacteria.

[0941] Pathogenic fungi causing infections treatable by methods of the disclosure include, but are not limited to, Candida (albicans, krusei, glabrata, tropicalis, etc.), Cryptococcus neoformans, Aspergillus (fumigatus. niger, etc.), Genus Mucorales (mucor, absidia, rhizophus). Sporothrix schenkii, Blastomyces dermatitidis, Paracoccidioides brasiliensis. Coccidioides immitis and Histoplasma capsulatum.

[0942] Pathogenic parasites causing infections treatable by methods of the disclosure include, but are not limited to, Entamoeba histolytica, Balantidium coli, Naegleriafowleri, Acanthamoeba sp.. Giardia lambia, Cryptosporidium sp., Pneumocystis carinii. Plasmodium vivax, Babesia microti, Trypanosoma bmcei, Trypanosoma cmzi. Leishmania donovani. Toxoplasma gondi, and Nippostrongylus brasiliensis. When more than one pharmaceutical agent is administered to a patient, they can be administered simultaneously, separately, sequentially, or in combination (e.g., for more than two agents).

[0943] Methods for the safe and effective administration of most of these chemotherapeutic agents are known to those skilled in the art. In addition, their administration is described in the standard literature. For example, the administration of many of the chemotherapeutic agents is described in the “Physicians' Desk Reference” (PDR, e.g., 1996 edition, Medical Economics Company, Montvale, NJ), the disclosure of which is incorporated herein by¬ reference as if set forth in its entirety.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0944] II. Immune-checkpoint therapies

[0945] Compounds of the present disclosure can be used in combination with one or more immune checkpoint inhibitors for the treatment of diseases, such as cancer or infections. Exemplary immune checkpoint inhibitors include inhibitors against immune checkpoint molecules such as CBL-B. CD20, CD28, CD40, CD70. CD 122, CD96. CD73, CD47, CDK2, CDK4, GITR, CSF1R, JAK, PI3K delta, PI3K gamma, TAM, arginase, HPK1, CD137 (also known as 4-1BB), ICOS, A2AR, B7-H3, B7-H4, BTLA, CTLA-4, LAG3, TIM3, TLR (TLR7 / 8), TIGIT, CD112R, VISTA, PD-1, PD-L1 and PD-L2. In some embodiments, the immune checkpoint molecule is a stimulatory checkpoint molecule selected from CD27, CD28, CD40, ICOS, 0X40, GITR and CD137. In some embodiments, the immune checkpoint molecule is an inhibitory checkpoint molecule selected from A2AR, B7-H3, B7-H4, BTLA, CTLA-4, IDO, KIR, LAG3, PD-1, TIM3, TIGIT, and VISTA. In some embodiments, the compounds provided herein can be used in combination with one or more agents selected from KIR inhibitors, TIGIT inhibitors, LA1R1 inhibitors, CD 160 inhibitors, 2B4 inhibitors and TGFR beta inhibitors.

[0946] In some embodiments, the compounds provided herein can be used in combination with one or more agonists of immune checkpoint molecules, e.g., 0X40, CD27, GITR. and CD 137 (also known as 4- IBB).

[0947] In some embodiments, the inhibitor of an immune checkpoint molecule is anti-PDl antibody, anti-PD-Ll antibody, or anti-CTLA-4 antibody.

[0948] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of PD-1 or PD-L1, e.g., an anti-PD-1 or anti-PD-Ll monoclonal antibody. In some embodiments, the anti-PD-1 or anti-PD-Ll antibody is nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, cemiplimab, atezolizumab, avelumab, tislelizumab, spartalizumab (PDR001), cetrelimab (JNJ-63723283), toripalimab (JS001), camrelizumab (SHR-1210), sintilimab (IBI308), AB122 (GLS-010), AMP-224, AMP-514 / MEDI-0680, BMS936559, JTX-4014. BGB-108, SHR-1210, MEDI4736, FAZ053, BCD-100. KN035, CS1001, BAT1306, LZM009, AK105, HLX10, SHR-1316, CBT-502 (TQB2450), A167 (KL-A167), STI-A101 (ZKAB001), CK-301, BGB-A333, MSB-2311, HLX20, TSR-042, or LY3300054. In some embodiments, the inhibitor of PD-1 or PD-L1 is one disclosed in U. S. Pat. Nos. 7,488,802, 7.943,743, 8,008.449, 8,168,757. 8,217, 149, WO 03042402, WO 2008156712, WO 2010089411, WO 2010036959, WO 2011066342, WO 2011159877, WOAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0949] 2011082400. or WO 2011161699, which are each incorporated herein by reference in its entirety.

[0950] In some embodiments, the antibody is an anti-PD-1 antibody, e.g., an anti-PD-1 monoclonal antibody. In some embodiments, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, spartalizumab, camrelizumab, cetrelimab, toripalimab, sintilimab, AB122. AMP-224. JTX-4014, BGB-108, BCD-100. BAT1306. LZM009, AK105, HLX 10, or TSR-042. In some embodiments, the anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, spartalizumab, camrelizumab, cetrelimab, toripalimab, or sintilimab. In some embodiments, the anti-PD-1 antibody is pembrolizumab. In some embodiments, the anti-PD-1 antibody is nivolumab. In some embodiments, the anti-PD-1 antibody is cemiplimab. In some embodiments, the anti-PD-1 antibody is spartalizumab. In some embodiments, the anti-PD-1 antibody is camrelizumab. In some embodiments, the anti-PD-1 antibody is cetrelimab. In some embodiments, the anti-PD-1 antibody is toripalimab. In some embodiments, the anti-PD-1 antibody is sintilimab. In some embodiments, the anti-PD-1 antibody is AB 122. In some embodiments, the anti-PD-1 antibody is AMP-224. In some embodiments, the anti-PD-1 antibody is JTX-4014. In some embodiments, the anti-PD-1 antibody is BGB-108. In some embodiments, the anti-PD-1 antibody is BCD-100. In some embodiments, the anti-PD-1 antibody is BAT1306. In some embodiments, the anti-PD-1 antibody is LZM009. In some embodiments, the anti-PD-1 antibody is AK.105. In some embodiments, the anti-PD-1 antibody is HLX 10. In some embodiments, the anti-PD-1 antibody is TSR-042. In some embodiments, the anti-PD-1 monoclonal antibody is nivolumab or pembrolizumab. In some embodiments, the anti-PD-1 monoclonal antibody is MGA012. In some embodiments, the anti-PDl antibody is SHR-1210. Other anti-cancer agent(s) include antibody therapeutics such as 4-1BB (e.g., urelumab. utomilumab). In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of PD-L1, e.g., an anti-PD-Ll monoclonal antibody. In some embodiments, the anti-PD-Ll monoclonal antibody is atezolizumab, avelumab, durvalumab, tislelizumab, BMS-935559, MEDI4736. atezolizumab (MPDL3280A; also known as RG7446), avelumab (MSB0010718C), FAZ053, KN035, CS1001, SHR-1316, CBT-502, A167, STI-A101, CK-301, BGB-A333, MSB-2311, HLX20, or LY3300054. In some embodiments, the anti-PD-Ll antibody is atezolizumab, avelumab, durvalumab, or tislelizumab. In some embodiments, the anti-PD-Ll antibody is atezolizumab. In some embodiments, the anti-PD-Ll antibody is avelumab. In some embodiments, the anti-PD-Ll antibody is durvalumab. In someAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0951] embodiments, the anti-PD-Ll antibody is tislelizumab. In some embodiments, the anti-PD-L1 antibody is BMS-935559. In some embodiments, the anti-PD-Ll antibody is MEDI4736. In some embodiments, the anti-PD-Ll antibody is FAZ053. In some embodiments, the anti-PD-Ll antibody is KN035. In some embodiments, the anti-PD-Ll antibody is CS1001. In some embodiments, the anti-PD-Ll antibody is SHR-1316. In some embodiments, the anti-PD-Ll antibody is CBT-502. In some embodiments, the anti-PD-Ll antibody is A167. In some embodiments, the anti-PD-Ll antibody is STI-A101. In some embodiments, the anti-PD-Ll antibody is CK-301. In some embodiments, the anti-PD-Ll antibody is BGB-A333. In some embodiments, the anti-PD-Ll antibody is MSB-2311. In some embodiments, the anti-PD-Ll antibody is HLX20. In some embodiments, the anti-PD-Ll antibody is LY3300054.

[0952] In some embodiments, the inhibitor of an immune checkpoint molecule is a small molecule that binds to PD-L1, or a pharmaceutically acceptable salt thereof. In some embodiments, the inhibitor of an immune checkpoint molecule is a small molecule that binds to and internalizes PD-L1, or a pharmaceutically acceptable salt thereof. In some embodiments, the inhibitor of an immune checkpoint molecule is a compound selected from those in US 2018 / 0179201, US 2018 / 0179197, US 2018 / 0179179, US 2018 / 0179202, US 2018 / 0177784, US 2018 / 0177870, US Ser. No. 16 / 369,654 (filed Mar. 29, 2019), and US Ser. No. 62 / 688,164. or a pharmaceutically acceptable salt thereof, each of which is incorporated herein by reference in its entirety.

[0953] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of KIR, TIGIT, LAIR1, CD160, 2B4 and TGFR beta.

[0954] In some embodiments, the inhibitor is MCLA-145.

[0955] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of CTLA-4, e g., an anti-CTLA-4 antibody. In some embodiments, the anti-CTLA-4 antibody is ipilimumab, tremelimumab, AGEN1884, or CP-675,206.

[0956] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of LAG3, e.g., an anti-LAG3 antibody. In some embodiments, the anti-LAG3 antibody is BMS-986016, LAG525, INCAGN2385, or eftilagimod alpha (IMP321).

[0957] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of CD73. In some embodiments, the inhibitor of CD73 is oleclumab.

[0958] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of TIGIT. In some embodiments, the inhibitor of TIGIT is OMP-31M32.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION

[0959] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of VISTA. In some embodiments, the inhibitor of VISTA is JNJ-61610588 or CA-170.

[0960] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of B7-H3. In some embodiments, the inhibitor of B7-H3 is enobi ituzumab, MGD009, or 8H9.

[0961] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of KIR. In some embodiments, the inhibitor of KIR is lirilumab or IPH4102.

[0962] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of A2aR. In some embodiments, the inhibitor of A2aR is CPI-444.

[0963] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of TGF-beta. In some embodiments, the inhibitor of TGF-beta is trabedersen, galusertinib, or M7824.

[0964] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of PI3K-gamma. In some embodiments, the inhibitor of PI3K-gamma is IPI-549.

[0965] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of CD47. In some embodiments, the inhibitor of CD47 is Hu5F9-G4 or TTI-621.

[0966] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of CD73. In some embodiments, the inhibitor of CD73 is MEDI9447.

[0967] In some embodiments, the inhibitor of an immune checkpoint molecule is an inhibitor of CD70. In some embodiments, the inh...

Claims

Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONWhat is claimed is:

1. A compound of Formula (I):(I) or a pharmaceutically acceptable salt thereof, wherein:n is 0, 1, 2, 3, 4, 5, or 6;p is 0, 1, 2, 3, 4, 5, or 6;each m is independently 1, 2, 3, or 4;is O or S, and Z is CR1; oris CR2, and Z is O or S;X is O, S, S(O)2, S(O)NRc, or N(-L-R4);L is a bond, C1-6alkylene, C(O), C(O)NRa, C(O)O, S(O), S(O)2, S(O)(=NRb), or S(O)2NRa;Ra, Rb, and Rcare each independently selected from H, Ci-6 alkyl, and Ci-ehaloalkyl; or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;Ring moiety A is 5-10 membered heteroaryl;when Y is O, then R1is selected from H, D, CN, halo, Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-10 cycloalkyl, 6-14 membered ary l, 4-15 membered heterocycloalkyl, 5-14 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-14 membered aryl-C1-4 alkyl, 4-15 membered heterocycloalkyl-Ci-4 alkyl, 5-14 membered heteroaryl-C 1.4 alkyl, ORbl, SRbl, NHORal, C(O)Rbl, C(O)NRclRdl, C(O)NRcl(ORal), C(O)ORal, OC(O)Rbl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONOC(O)NRclRdl, NRclRdl, NRclNRclRdl. NRclC(O)Rbl, NRclC(O)ORal. NRclC(O)NRclRdl, C(=NRel)Rbl, C(=NRel)NRclRdl, NRclC(=NRel)NRclRdl, NRclC(=NRel)Rbl, NRclS(O)NRclRdl, NRclS(O)Rbl, NRclS(O)2Rbl, NRclS(O)(=NRel)Rbl, NRclS(O)2NRclRdl, S(O)Rbl, S(O)NRclRdl, S(O)2Rbl, S(O)2NRclRdl, OS(O)(=NRel)Rbl, OS(O)2Rbl, S(O)(=NRel)Rbl, SF5, P(O)RflRgl, OP(O)(ORhl)(ORil), P(O)(ORhl)(ORil), and BRjlRkl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-14 membered aryl, 4-15 membered heterocycloalkyl, 5-14 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-14 membered aryl-Ci-4 alkyl, 4-15 membered heterocycloalkyl-Ci-4 alky l, and 5-14 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; orwhen Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci.6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-14 membered aryl, 4-15 membered heterocycloalkyl, (R1A2)m-5-14 membered heteroaryl, (R1A)m-C3-10 cycloalkyl-C 1-4 alkyl, (C3-10 cy cl oalkyl)-(R1A1)m-C 1-4 alkyl, 6-14 membered aryl-C 1-4 alkyl, 4-15 membered heterocycloalkyl-C 1-4 alkyl, 5-14 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, NHORal, C(O)Rbl, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclNRclRdl, NRclC(O)ORal, NRclC(O)NRclRdl, C(=NRel)Rbl, C(=NRel)NRclRdl, NRclC(=NRel)NRclRdl, NRclC(=NRel)Rbl, NRclS(O)NRclRdl, NRclS(O)Rbl, NRclS(O)2Rbl, NRclS(O)(=NRel)Rbl, NRclS(O)2NRclRdl, S(O)Rbl, S(O)NRclRdl, S(O)2Rbl. OS(O)(=NRel)Rbl. OS(O)2Rbl,S(O)(=NRel)Rbl, SF5, P(O)RflRgl, OP(O)(ORhl)(ORn), P(O)(ORhl)(ORil), and BRjlRkl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-14 membered aryl, 4-15 membered heterocycloalkyl, 6-14 membered aryl-C 1-4 alkyl, 4-15 membered heterocycloalkyl-C 1-4 alkyl, and 5-14 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-C1-6haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-14 membered heteroaryl portion of said (R1A2)m-5-14 membered heteroaryl, (ii) the C3-10 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-10 cycloalkyl-C 1-4 alkyl, and (iii) the C3-10 cycloalkyl-C 1-4 alkyl portion of (C3-10 cycloalkyl)-(R1A1)m-Ci-4 alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents;each Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONalkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;or, any Rcland Rdlattached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each Rb1is independently selected from C1-6 alkyl, C1-6 haloalkyl. C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroary I-C1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each Relis independently selected from H. OH, CN, Ci-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroary I-C1-4 alkyl;each Rfland Rglare independently selected from H. Ci-6 alkyl, C1-6 alkoxy. C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryd, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl;each Rhland R11is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryd, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyd;each Rl1and Rklis independently selected from OH, Ci-6 alkoxy, and Ci-6 haloalkoxy; or any R'1and Rklattached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-6 alkyd and C 1-6 haloalkyl; each R1Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, NHORa11, C(O)Rb11, C(O)NRcllRd11, C(O)NRcll(ORa11), C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllNRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, C(=NRell)Rb11, C(=NRell)NRcllRdll, NRcllC(=NRell)NRcllRd11, NRcllC(=NRell)Rb11, NRcllS(O)NRcllRd11, NRollS(O)Rb11, NRcllS(O)2Rb11, NRcllS(O)(=NRell)Rb11, NRcllS(O)2NRcllRd11, S(O)Rb11. S(O)NRcllRd11, S(O)2Rb11. S(O)2NRcllRd11.OS(O)(=NRell)Rb11, OS(O)2Rb11, S(O)(=NRell)Rb11, SF5, P(O)RfllRg11, OP(O)(ORhll)(ORin), P(O)(ORhll)(ORin), and BRjllRk11, wherein said Ci-6alky l, C2-6alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A1is independently selected from CN, C2-6 alkenyl, C2-6 alky nyl, (R1B)m-Ci-4 alkoxy. (R1B)m-C3-7 cycloalkyl. phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORm11, SRa11, NHORa11, C(O)Rb11, C(O)NRcllRd11, C(O)NRcll(ORa11), C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllNRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRdll, C(=NRell)Rbll, C(=NRel 1)NRc11Rd11, NRcllC(=NRell)NRcllRd11, NRcllC(=NRell)Rb11, NRcllS(O)NRcllRd11. NRcllS(O)Rb11, NRcllS(O)2Rb11, NRcllS(O)(=NRell)Rb11, NRcllS(O)2NRcllRd11, S(O)Rb11, S(O)NRcllRd11,S(O)2Rb11, S(O)2NRcllRd11, OS(O)(=NRell)Rbll, OS(O)2Rb11, S(O)(=NRell)Rb11, SF5, P(O)RfllRg11, OP(O)(ORhll)(ORin), P(O)(ORhll)(ORin), and BRjllRk11, wherein said C2-6alkenyl, C2-6alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A2is independently selected from CN, NO2, (R1B)m-Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl. (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORm11, SRa11, NHORa11, C(O)Rb11, C(O)NRcllRd11, C(O)NRcll(ORa11), C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11. NRcllNRcllRd11. NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, C(=NRell)Rb11, C(=NRell)NRcllRd11, NRcllC(=NRell)NRcllRd11,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONNRcllC(=NRell)Rb11, NRcllS(O)NRcllRd11, NRcllS(O)Rb11, NRcllS(O)2Rb11, NRcllS(O)(=NRell)Rb11, NRcllS(O)2NRcllRd11, S(O)Rb11, S(O)NRcllRd11, S(O)2Rb11, S(O)2NRcllRd11, OS(O)(=NRell)Rb11, OS(O)2Rbll, S(O)(=NRell)Rb11, SF5, P(O)RfllRg11, OP(O)(ORhll)(ORin), P(O)(ORhll)(ORin), and BRjllRk11, wherein said C2-6alkenyl, C2-6alkynyl, Ci-6 haloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci.4 alkyd are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A3is independently selected from halo, OH, C1-4 alkoxy, and C3-7 cycloalkyl, wherein said C1-4 alkoxy and C3-7 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A4is independently selected from halo, OH, C1-6 alkyl, C1-4 alkoxy, and C3-7 cycloalkyl, wherein said C1-6 alkyl, C1.4 alkoxy, and C3-7 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Ral1, Rcl1, and Rdl1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky 1, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C1-4 alkyl, ph enyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;or, any Rcl1and Rdl1attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rbl1is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rel1is independently selected from H, OH. CN, C1-6 alkyl. C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;each Rfl1and Rgl1is independently selected from H, Ci-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;each Rhl1and R111is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;each Rjl1and Rkl1is independently selected from OH, C1-6alkoxy, and C1-6haloalkoxy;or any RJ11and Rkl1attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2. 3, or 4 substituents independently selected from C1-6 alkyl and C 1-6 haloalkyl; each Rml1is independently selected from C1-6alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaiy I. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1Bis independently selected from halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa12, SRa12, NHORa12, C(O)Rh12, C(O)NRc12Rd12, C(O)NRcl2(ORa12), C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRcl2Rdl2, NRcl2NRcl2Rdl2, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, C(=NRel2)Rb12, C(=NRel2)NRcl2Rd12, NRcl2C(=NRel2)NRcl2Rd12, NRcl2C(=NRel2)Rb12, NRcl2S(O)NRcl2Rd12, NRcl2S(O)Rb12, NRcl2S(O)2Rb12, NRcl2S(O)(=NRel2)Rb12, NRcl2S(O)2NRcl2Rd12, S(O)Rb12, S(O)NRcl2Rd12, S(O)2Rb12, S(O)2NRcl2Rd12, OS(O)(=NRel2)Rb12, OS(O)2Rb12, S(O)(=NRel2)Rb12, SF5, P(O)Rfl2Rg12, OP(O)(ORhl2)(ORi12), P(O)(ORhl2)(ORi12), and BRjl2Rk12, wherein said Ci-6alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ral2, Rcl2, and Rdl2is independently selected from H, Ci-6 alkyd, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky 1, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyd, phenyl-C 1-4 alky 1, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroary 1-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;or, any Rcl2and Rdl2attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rbl2is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyd, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroary 1-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rel2is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalk d, 5-6 membered heteroary!, C3-7 cycloalky I-C1-4 alky 1, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroary 1-C 1-4 alkyl;each Rfl2and Rgl2is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalk d, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroary!, C3-7 cycloalkyl-C 1-4 alkyd, phenyl-C 1-4 alky 1, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroary 1-C 1-4 alkyl;each Rhl2and Ril2is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary!, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyd-C 1-4 alk d, and 5-6 membered heteroary 1-C 1-4 alkyd;each Rjl2and Rkl2is independently selected from OH. C1-6 alkoxy, and C1-6 haloalkoxy;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONor any Rjl2and Rkl2attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-6 alkyd and Ci-6 haloalkyl;R2is selected from H, D, halo, CN, Ci-6 alkyl, Ci-6 haloalky 1, C3-4 cycloalkyl, C3-4 cycloalkyl-Ci-4 alkyl, ORb2, SRb2, NHORa2, C(O)Rb2, C(O)NRc2Rd2, C(O)NRc2(ORa2), C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2. NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, C(=NRe2)Rb2, C(=NRe2)NRc2Rd2, NRc2C(=NRe2)NRc2Rd2, NRc2C(=NRe2)Rb2, NRc2S(O)NRc2Rd2, NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)(=NRe2)Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said C1-6alkyl, Ci-6 haloalkyl, C3-4 cycloalkyl, and C3-4cycloalkyl-Ci-4 alky l are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ra2, Rc2, and Rd2is independently selected from H, C1-6alkyl, C1-6haloalkyl, and C3-4 cycloalkyl, wherein said C1-6alkyl, C1-6haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2. 3, or 4 independently selected RGsubstituents;each Rb2is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Re2is independently selected from H, OH, CN, C 1-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, and C 1-6 haloalkoxy;each R3is independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa3. SRa3. NHORa3, C(O)Rb3, C(O)NRc3Rd3, C(O)NRc3(ORa3), C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3C(=NRe3)Rb3, NRc3S(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)(=NRe3)Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3, wherein said Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ra3, Rc3. and Rd3is independently selected from H. Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONcycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1.4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2. 3, or 4 independently selected RGsubstituents;each Re3is independently selected from H, OH, CN, Ci-6 alkyd, C 1-6 alkoxy, Ci-6 haloalkyl, and C 1-6 haloalkoxy;R4is selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-C 1-4 alkyl, 6-10 membered aryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;each R4Ais independently selected from oxo, D, halo, CN, NO2, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C1-4alkyl, ORa41, SRa41, NHORa41, C(O)Rb41, C(O)NRc41Rd41, C(O)NRc41(ORa41), C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41NRc41Rd41, NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, C(=NRe41)Rb41, C(=NRe41)NRc41Rd41, NRc41C(=NRe41)NRc41Rd41, NRc41C(=NRe41)Rb41, NRc41S(O)NRc41Rd41, NRc41S(O)Rb41, NRc41S(O)2Rb41, NRc41S(O)(=NRe41)Rb41, NRc41S(O)2NRc41Rd41, S(O)Rb41, S(O)NRc41Rd41, S(O)2Rb41, S(O)2NRc41Rd41, OS(O)(=NRe41)Rb41, OS(O)2Rb41, and S(O)(=NRe41)Rb41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONalkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalky l. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;or, any Rc41and Rd41attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Rb41is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyd, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Re41is independently selected from H, OH. CN, C1-6 alkyl. C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl;each R4Bis independently selected from D, halo, CN, NO2, C1-6 alky l, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroary l-Ci-4 alkyl, ORa42, SRa42, NHORa42, C(O)Rb42, C(O)NRc42Rd42, C(O)NRc42(ORa42). C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, C(=NRe42)Rb42, C(=NRe42)NRc42Rd42, NRc42C(=NRe42)NRc42Rd42, NRc42C(=NRe42)Rb42, NRc42S(O)NRc42Rd42, NRc42S(O)Rb42, NRc42S(O)2Rb42, NRc42S(O)(=NRe42)Rb42, NRc42S(O)2NRc42Rd42, S(O)Rb42, S(O)NRc42Rd42, S(O)2Rb42, S(O)2NRc42Rd42, OS(O)(=NRe42)Rb42, OS(O)2Rb42, and S(O)(=NRe42)Rb42, wherein said C1-6 alkyl, C1-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONalkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, Ci-6 haloalky l. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rb42is independently selected from C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2. 3, or 4 independently selected RGsubstituents;each Re42is independently selected from H, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl;each R5is independently selected from D, halo, NO2, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyd, 6-10 membered aryl, 4-10 membered heterocycloalkyd, 5-10 membered heteroaryl, C3-10 cycloalky I-C1-4 alkyl, 6-10 membered aryd-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-Ci-4 alkyl, ORa5, SRa5, NHORa5, C(O)Rb5, C(O)NRc5Rd5. C(O)NRc5(ORa5), C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, C(=NRe5)Rb5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5C(=NRe5)Rb5, NRc5S(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)(=NRe5)Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, S(O)2NRc5Rd5, OS(O)(=NRe5)Rb5, OS(O)2Rb5, S(O)(=NRe5)Rh5, SF5, P(O)Rf5Rg5, OP(O)(ORh5)(ORi5), P(O)(ORh5)(ORi5), and BRj5Rk5, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalky 4, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONalkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R5Asubstituents;each Ra5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered ar l. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl. 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1.4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyL C3- 10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C 1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alky 1, and 5-10 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R5Asubstituents;or, any Rc5and Rd5attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyL C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alky l, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1. 2, 3, or 4 independently selected R5Asubstituents;each Re5is independently selected fromH, OH, CN, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;each Rf5and Rg5is independently selected from H, C1-6 alky l, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;each Rh5and Ri5is independently selected fromH, Ci-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered ary l, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl. 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach Rj5and Rk5is independently selected from OH. Ci-6 alkoxy, and Ci-6 haloalkoxy; or, any Rj5and Rk5attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from Ci-6 alky l and Ci-6 haloalkyl; each R5Ais independently selected from D, halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyd, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-Ci-4 alkyl, ORa51, SRa51, NH0Ra51, C(O)Rb51, C(O)NRc51Rd51, C(O)NRc51(ORa51), C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, C(=NRe51)Rb51, C(=NRe51)NRc51Rd51, NRc51C(=NRe51)NRc51Rd51, NRc51C(=NRe51)Rb51, NRc51S(O)NRc51Rd51, NRc51S(O)Rb51, NRc51S(O)2Rb51, NRc51S(O)(=NRe51)Rb51, NRc51S(O)2NRc51Rd51, S(O)Rb51, S(O)NRc51Rd51, S(O)2Rb51, S(O)2NRc51Rd51, OS(O)(=NRe51)Rb51, OS(O)2Rb51, S(O)(=NRe51)Rb51. SF5, P(O)Rf51Rg51,OP(O)(ORh51)(OR‘51), P(O)(ORb51)(ORi51), and BRj51Rk51, wherein said C1-6alkyl, C2-6 alkenyl, C2.6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaiyl-Ci-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R5Bsubstituents;each Ra51, Rc51, and Rd51is independently selected from H, Ci-6 alky 1, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alky nyl, C3-10 cycloalkyl, 6-10 membered ary l, 4-10 membered heterocycloalky l, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alky nyl, Ci-6 haloalky l, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R5Bsubstituents;or, any Rc51and Rd51attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, which is optionally substituted with 1, 2. 3, or 4 independently selected R5Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach Rb51is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl -C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered hctcrocycloalkyl-C 1-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;each Re51is independently selected from H, OH. CN, C1-6 alkyl. C1-6 alkoxy, C1-6 haloalkyl, C 1.6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alky l, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;each Rf51and Rg51is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alky l, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-Ci-4 alkyl;each Rh51and Ri51is independently selected from H, C1-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl;each Rj51and Rk51is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;or, any Rj51and Rk51attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2. 3, or 4 substituents independently selected from C1-6 alkyl and C 1-6 haloalkyl;each R5Bis independently selected from D, halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa52. SRa52, NHORa52. C(O)Rb52, C(O)NRc52Rd52, C(O)NRc52(ORa52), C(O)ORa52, OC(O)Rb52, OC(O)NRc52Rd52, NRc52Rd52, NRc52NRc52Rd52NRc52C(O)Rb52, NRc52C(O)ORa52, NRc52C(O)NRc52Rd52, C(=NRe52)Rb52, C(=NRe52)NRc52Rd52, NRc52C(=NRe52)NRc52Rd52, NRc52C(=NRe52)Rb52, NRc52S(O)NRc52Rd52, NRc52S(O)Rb52, NRc52S(O)2Rb52, NRc52S(O)(=NRe52)Rb52, NRc52S(O)2NRc52Rd52, S(O)Rb52, S(O)NRc52Rd52, S(O)2Rb52, S(O)2NRc52Rd52,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONOS(O)(=NRe52)Rb52, OS(O)2Rb52, S(O)(=NRe52)Rb52, SF5, P(O)Rf52Rg52, OP(O)(ORh52)(ORi52), P(O)(ORh52)(ORi52), and BRj52Rk52, wherein said C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected RGsubstituents;each Ra52, Rc52, and Rd52is independently selected from H, Ci-6 alkyd, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;or, any Rc52and Rd52attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, which is optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rb52is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl -Ci -4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyd, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Re52is independently selected from H, OH. CN, Ci-6 alkyl. Ci-6 alkoxy, Ci-6 haloalkyl, C 1-6 haloalkoxy, C2-6 alkenyl. C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl;each Rf52and Rg52is independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, C 1-6 haloalkoxy. C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl;each Rh52and Ri52is independently selected from H, Ci-6 alky l, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl;each Rj52and Rk52is independently selected from OH, C1-6 alkoxy, and C1-6 haloalkoxy;or, any Rj52and Rk52attached to the same B atom, together with the B atom to which they are attached, form a 5- or 6-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from C1-6 alkyl and Ci-ehaloalkyl; and each RGis independently selected from OH, NO2, CN, halo, C1-3 alky l, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alky l, C3-4 cycloalkyl, C1-3 alkoxy, C1.3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino. thio, Ci-3 alkylthio, C1-3 alkylsulfinyl, C1.3 alkylsulfonyl, carbamyl, C1.3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkyd carbonyl, C1-3 alkoxy carbonyl, C1-3 alkylcarbonyloxy, C1-3 alky Icarbonylamino, C1-3 alkoxy carbonylamino, C1-3 alkylaminocarbonyloxy, C1-3 alky lsulfonylamino, aminosulfonyl, C 1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alky laminocarbonylamino, and di(Ci-3 alkyl)aminocarbonyl amino.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein n is 0, 1, or 2.

3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein n is O or l.

4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein n is 1.

5. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein p is 0. 1, 2, 3. 4, or 5.

6. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein p is 0, 1, 2, 3, or 4.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION7. The compound of any one of claims 1-4. or a pharmaceutically acceptable salt thereof, wherein p is 0, 1, 2, or 3.

8. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein p is 0.

9. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein p is 1.

10. The compound of any one of claims 1-4. or a pharmaceutically acceptable salt thereof, wherein p is 2.

11. The compound of any one of claims 1-4, or a pharmaceutically acceptable salt thereof, wherein p is 3.

12. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt thereof, wherein each m is independently 1 or 2.

13. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt thereof, wherein X is O, S(O)2, S(O)NRC, or N(-L-R4).

14. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt thereof, wherein X is O, S(O)2, or N(-L-R4).

15. The compound of any one of claims 1-12. or a pharmaceutically acceptable salt thereof, wherein X is O or N(-L-R4).

16. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt thereof, wherein X is O.

17. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt thereof, wherein X is S.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION18. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt thereof, wherein X is S(O)2.

19. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt thereof, wherein X is S(O)NRC.

20. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt thereof, wherein X is N(-L-R4).

21. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein L is C(O), C(O)NRa, C(O)O, S(O), S(O)2, or S(O)2NRa.

22. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein L is C(O), C(O)O, S(O)2. or S(O)2NRa.

23. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein L is a bond.

24. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein L is Ci-6 alkylene.

25. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein L is C(O).

26. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein L is C(O)NRa.

27. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein L is C(O)O.

28. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein L is S(O).Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION29. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein L is S(O)2.

30. The compound of any one of claims 1-20, or a pharmaceutically acceptable salt thereof, wherein L is S(O)(=NRb).

31. The compound of any one of claims 1 -20, or a pharmaceutically acceptable salt thereof, wherein L is S(O)2NRa.

32. The compound of any one of claims 1-31, or a pharmaceutically acceptable salt thereof, wherein Ra, Rb, and Rcare each independently selected from H and C1.3 alkyl.

33. The compound of any one of claims 1-31, or a pharmaceutically acceptable salt thereof, wherein Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

34. The compound of any one of claims 1-31, or a pharmaceutically acceptable salt thereof, wherein Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

35. The compound of any one of claims 1-34, or a pharmaceutically acceptable salt thereof, wherein Ring moiety A is 5-9 membered heteroaryl.

36. The compound of any one of claims 1-34, or a pharmaceutically acceptable salt thereof, wherein Ring moiety A is 5-6 membered heteroaryl.

37. The compound of any one of claims 1-34, or a pharmaceutically acceptable salt thereof, wherein Ring moiety A is a pyrazole ring, a thiazole ring, an isothiazole ring, an oxazole ring, an isoxazole ring, an oxadiazole ring, a thiodiazoloring, a pyridine ring, a pyridazine ring, a pyrazine ring, a pyrimidine ring, an indazole ring, an indole ring, aAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONpyrazolopyridine ring, a pyrrolopyridine ring, a pyrazolopyrimidine ring, or a pyrrolopyrmidine ring.

38. The compound of any one of claims 1-34, or a pharmaceutically acceptable salt thereof, wherein Ring moiety A is a pyrazole ring, a thiazole ring, a pyridine ring, a pyridazine ring, or an indazole ring.

39. The compound of any one of claims 1-34, or a pharmaceutically acceptable salt thereof, wherein Ring moiety A is a pyrazole ring, a thiazole ring, an isothiazole ring, a pyridine ring, a pyridazine ring, or an indazole ring.

40. The compound of any one of claims 1-39, or a pharmaceutically acceptable salt thereof, wherein when Y is O, then R1is selected from H, D, CN, halo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, 6-10 membered ary l, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, 6-10 membered aryl-C1-4 alkyl, 4-10 membered heterocycloalkyl-Ci-4 alkyl, 5-10 membered heteroaryl-Ci-4 alkyl. ORbl, SRbl, C(O)Rbl, C(O)NRclRdl, C(O)ORal, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)Rbl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl, S(O)2Rbl, and S(O)2NRclRdl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl. 6-10 membered aryl. 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl -C 1-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, and 4-10 membered heterocycloalkyl-C 1-4 alkyl are each optionally7substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

41. The compound of any one of claims 1-39, or a pharmaceutically acceptable salt thereof, wherein when Y is O, then R1is selected from H, D, CN, halo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky7!, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, C(O)Rbl, C(O)NRclRdl, C(O)ORal, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)Rbl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl, S(O)2Rbl, and S(O)2NRclRdl, wherein said Ci-6 alky l, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONmembered heteroaryl-C 1.4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Asubstituents.

42. The compound of any one of claims 1-39, or a pharmaceutically acceptable salt thereof, wherein when Y is O, then R1is selected from H, D, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, andNRclRdl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl -C 1-4 alkyl, and 5-6 membered heteroaryl -Ci -4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

43. The compound of any one of claims 1-39, or a pharmaceutically acceptable salt thereof, wherein when Y is O, then R1is selected from H, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocycloalkyl-Ci-i alkyl, and ORbl, wherein said C2-6 alkynyl. phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

44. The compound of any one of claims 1-39, or a pharmaceutically acceptable salt thereof, wherein when Y is S, then R1is selected fromH, D, halo, (R1A1)m-Ci-6 alky l, (R1A1)m-Ci.6 haloalkyl. C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, 6-10 membered aryl, 4-10 membered heterocycloalkyl, (R1A2)m-5-10 membered heteroaryl, (R1A)m-C3-10 cycloalkyl-C 1-4 alkyl, (C3-10 cycloalkyl)-(R1A1)m-Ci-4 alkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyl-C1-4alkyl, 5-10 membered heteroaryl-C1-4alkyl, ORbl, SRbl, C(O)Rbl, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)ORal, NRclC(O)NRclRdl. NRclS(O)2Rbl, NRclS(O)2NRclRdl, and S(O)2Rbl. wherein said C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl. 6-10 membered aryl, 4-10 membered heterocycloalkyl, 6-10 membered aryl-Ci-4 alkyl, 4-10 membered heterocycloalkyd-C 1-4 alkyl, and 5-10 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-C1-6 haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONsubstituents; and wherein (i) the 5-10 membered heteroaryl portion of said (R1A2)m-5-10 membered heteroaryl, (ii) the C3-10 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-10cycloalkyl-C1-4alkyl, and (iii) the C3-10-cycloalkyl-C1-4alkyl portion of (C3-10cycloalkyl)-(R1A1)m-C1-4alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents.

45. The compound of any one of claims 1-39, or a pharmaceutically acceptable salt thereof, wherein when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl, (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl, (C3-7cycloalkyl)-(R1A1)m-C1-4alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, C(O)Rbl, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl, and S(O)2Rbl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-Ci-6 haloalky l are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, (ii) the C3-7 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl, and (iii) the C3-7 cycloalkyl-C1-4 alkyl portion of (C3-7 cycloalky l)-(R1A1)m-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents.

46. The compound of any one of claims 1-39, or a pharmaceutically acceptable salt thereof, wherein when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-C1-6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl. (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, andNRclRdl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-C1-6haloalkyl are each optionallyAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONsubstituted by 1, 2. or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, and (ii) the C3-7 cy cl oalkyl-C 1-4 alkyl portion of (R1A)m-C3-7cycloalkyl-C1-4alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents.

47. The compound of any one of claims 1-39, or a pharmaceutically acceptable salt thereof, wherein when Y is S, then R1is selected from H, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl, 4-7 membered heterocycloalkyl-C1-4alkyl, and ORbl, wherein said C2-6 alkynyl, 4-7 membered heterocycloalkyl, phenyl, and 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R1Asubstituents; and wherein the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl is optionally substituted by 1, 2, or 3 independently selected R1A4substituents.

48. The compound of any one of claims 1-47, or a pharmaceutically acceptable salt thereof, wherein:each Ral, Rcl, and Rdlis independently selected from H, C1-6 alky l, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each Rblis independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each R1Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONC(O)NRcllRd11, C(O)ORa11, OC(O)Rb11. OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;each Ral1, Rcl1, and Rdl1is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rbl1is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2.6 alkenyl, C2.6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1Bis independently selected from halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRcl2Rd12, NRcl2C(O)Rb12. NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12. S(O)2Rb12, and S(O)2NRcl2Rd12, wherein said Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ral2, Rcl2, and Rdl2is independently selected from H, C1-6alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1. 2, 3, or 4 independently selected RGsubstituents;each Rbl2is independently selected from C1-6alkyl and C1-6haloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;when present, each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION5-6 membered heteroaryl, phenyl-Ci-4 alkyl. 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C1-4alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcl1Rd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;when present, each R1A2is independently selected from CN. NO2, (R1B)m-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, 5-6 membered heteroaryl-C1-4alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11. NRcllS(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)2Rb11. and S(O)2NRcllRd11, wherein said C2-6alkenyl, C2-6alkynyl, C1-6 haloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;when present, each R1A3is independently selected from halo, OH, and C1-4 alkoxy, wherein said C1-4 alkoxy is optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents; andwhen present, each R1A4is independently selected from halo, OH. C1-6 alkyl, and C1-4 alkoxy, wherein said C1-6 alkyl and C1.4 alkoxy are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents; andwhen present, each Rm11is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents.

49. The compound of any one of claims 1-47, or a pharmaceutically acceptable salt thereof, wherein:Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach Ral, Rcl. and Rdlis independently selected from H. Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, wherein said C1-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl -C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each Rblis independently selected from Ci-6 alky 1, Ci-6 haloalky l, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl -Ci -4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alky 1, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each R1Ais independently selected from halo, CN. C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11. OC(O)NRc11Rd11, NRc11Rd11, NRcl1C(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11. and S(O)2NRcl1Rd11, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Ral1, Rcl1, and Rdl1is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach Rbl1is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1Bis independently selected from halo, CN, NO2, C1-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRcl2Rd12, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRcl2Rd12;each Ral2, Rcl2. and Rdl2is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;each Rbl2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;when present, each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcl1Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcl1Rd11, NRcl1Rd11, NRcl1C(O)Rb11, NRcl1C(O)ORa11, NRcl1C(O)NRcl1Rd11, NRcl1S(O)2Rb11, NRcl1S(O)2NRcl1Rd11, S(O)2Rb11, and S(O)2NRcl1Rd11, wherein said C2-6 alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;when present, each R1A2is independently selected from CN, NO2. (R1B)m-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl. 5-6 membered heteroaryl-C 1-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRellC(O)NRcllRd11. NRcllS(O)2Rb11, NRcllS(O)2NRcllRdllS(O)2Rb11, and S(O)2NRcl1Rd11, wherein said C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalky l, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONwhen present, each R1A3is independently selected from halo, OH, and C1-4alkoxy; when present, each R1A4is independently selected from halo, OH, Ci-6 alkyl, and C1-4 alkoxy; andwhen present, each Rml1is independently selected from C2-6alkenyl, C2-6alkynyl, C3-5cycloalkyl, and 4-5 membered heterocycloalkyl.

50. The compound of any one of claims 1-49, or a pharmaceutically acceptable salt thereof, wherein R2is selected from H, D, halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, C3-4 cycloalky l-Ci-4 alkyl, ORb2, SRb2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2. NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said C1-6alkyl, C1-6haloalkyl, C3-4 cycloalkyl, and C3-4 cycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

51. The compound of any one of claims 1-49. or a pharmaceutically acceptable salt thereof, wherein R2is selected from H, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

52. The compound of any one of claims 1-49, or a pharmaceutically acceptable salt thereof, wherein R2is selected from H, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl.

53. The compound of any one of claims 1-49, or a pharmaceutically acceptable salt thereof, wherein R2is H.

54. The compound of any one of claims 1-53, or a pharmaceutically acceptable salt thereof, wherein each Ra2, Rc2, and Rd2is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl; and each Rb2is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl.

55. The compound of any one of claims 1-53, or a pharmaceutically acceptable salt thereof, wherein each Ra2, Rc2. and Rd2is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and each Rb2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION56. The compound of any one of claims 1-55, or a pharmaceutically acceptable salt thereof, wherein each R3is independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)NRc3(ORa3), C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3, wherein said C1-6alkyl, C1-6haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

57. The compound of any one of claims 1-55, or a pharmaceutically acceptable salt thereof, wherein each R3is independently selected from halo, CN, Ci-6 alky l, Ci-6 haloalkyl. ORa3, and NRc3Rd3, wherein said Ci-6 alkyl and Ci-6 haloalkyl, and C3-4 cy cloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents.

58. The compound of any one of claims 1-55, or a pharmaceutically acceptable salt thereof, wherein each R3is independently selected from halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa3, and NRc3Rd3, wherein said Ci-6 alkyl and Ci-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1 RGsubstituent.

59. The compound of any one of claims 1-55, or a pharmaceutically acceptable salt thereof, wherein each R3is independently selected from Ci-6 alkyl, Ci-6 alky lene-ORa3, Ci-6 alkylene-NRc3Rd3, ORa3. and NRc3Rd3.

60. The compound of any one of claims 1-55, or a pharmaceutically acceptable salt thereof, wherein each R3is independently selected from Ci-6 alkylene-ORa?, Ci-6 alkylene-NRc3Rd3, ORa3. and NRc3Rd3.

61. The compound of any one of claims 1-55, or a pharmaceutically acceptable salt thereof, wherein each R3is independently selected from Ci-6 alky l, Ci-6 alkyd ene-OH and OH.

62. The compound of any one of claims 1-55, or a pharmaceutically acceptable salt thereof, wherein each R3is independently selected from Ci-6 alkylene-OH and OH.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION63. The compound of any one of claims 1-62, or a pharmaceutically acceptable salt thereof, wherein each Ra3, Rc3, and Rd3is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said Ci-6 alky l and Ci-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents; and each Rb3is independently selected from Ci-6 alkyl and Ci-6 haloalkyl. which are each optionally substituted with 1, 2, 3. or 4 independently selected RGsubstituents.

64. The compound of any one of claims 1-62, or a pharmaceutically acceptable salt thereof, wherein each Ra3, Rc3, and Rd3is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; and each Rb3is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

65. The compound of any one of claims 1-62, or a pharmaceutically acceptable salt thereof, wherein each Ra3, Rc3. and Rd3is independently selected from H and CH3; and each Rb3is CH3.

66. The compound of any one of claims 1-65, or a pharmaceutically acceptable salt thereof, wherein R4is selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alky l, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

67. The compound of any one of claims 1-65, or a pharmaceutically acceptable salt thereof, wherein R4is selected fromH, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C3-7 cycloalkyl-C 1-4 alkyl, wherein said Ci-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C3-10 cycloalkyl-Ci-4 alkyd are each optionally substituted by' 1, 2, 3, or 4 independently selected R4Asubstituents.

68. The compound of any one of claims 1-65, or a pharmaceutically acceptable salt thereof, wherein R4is selected fromH, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, and 5-6 membered heteroaryl, wherein said Ci-6 alkyl, Ci-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONhaloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents.

69. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein:each R4Ais independently selected from oxo, D, halo, CN, Ci-6 alky l, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyd, Ci-6 haloalky 1, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alky 1, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2. 3, or 4 independently selected R4Bsubstituents;each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, pheny l, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa42, SRa42, C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONOC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42C(O)Rb42. NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyd, and Ci-6 haloalky 1; andeach Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

70. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein:each R4Ais independently selected from D, halo, CN, Ci-6 alky l, Ci-6 haloalky 1, C3-7 cycloalky l, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said C1-6 alkyl, C1-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41. and Rd41is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyd, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONcycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa42, SRa42, C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl; andeach Rb42is independently selected from C1-6 alkyl and C1-6 haloalkyl.

71. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein:each R4Ais independently selected from oxo, D, halo, CN, Ci-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41. NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alky 1, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alky l, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2. 3, or 4 independently selected R4Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. and C3-4 cycloalkyl, ORa42, SRa42, C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl; andeach Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

72. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein:each R4Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41. NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroar l-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alky l, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaiyl-C1-4 alkyl, which are each optionally substituted with 1, 2. 3, or 4 independently selected R4Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalky 1. and C3-4 cycloalkyl, ORa42, SRa42, C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl; andeach Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

73. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein:each R4Ais independently selected from oxo, D, halo, CN, Ci-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa41, and NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41. and Rd41is independently selected from H, Ci-6 alky l, and Ci-6 haloalkyl;each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1 or 2 independently selected R4Bsubstituents;each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. ORa42and NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; andeach Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

74. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein:each R4Ais independently selected from D, halo, CN, Ci-6 alky l, Ci-6 haloalk 1, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalky I-C1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONmembered heteroaryl-Ci-4 alkyl, ORa41, and NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1.4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41. and Rd41is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1 or 2 independently selected R4Bsubstituents;each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. ORa42and NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalky l; andeach Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

75. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein each R4Ais independently selected from oxo, halo, CN, Ci-6 alkyl, Ci-e haloalkyl, and C3-4 cycloalkyl, wherein said Ci-6 alkyl, Ci-6 haloalky l, and C3-4 cycloalkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R4Bsubstituents; each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa42and NRc42Rd42; and each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl.

76. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein each R4Ais independently selected from halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents; each R4Bis independently selected fromD, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl. ORa42and NRc42Rd42; and each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

77. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein each R4Ais independently selected from oxo, halo. CN, Ci-6 alkyl, Ci-6 haloalkyl, and C3.4 cycloalkyl.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION78. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein each R4Ais independently selected from halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl.

79. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein each R4Ais independently selected from oxo, halo, CN, C1-6 alkyl, and Ci-6 haloalkyl.

80. The compound of any one of claims 1-68, or a pharmaceutically acceptable salt thereof, wherein each R4Ais independently selected from halo, CN, C1-6 alkyl, and C1-6 haloalkyl.

81. The compound of any one of claims 1-80, or a pharmaceutically acceptable salt thereof, wherein each R5is independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalky l, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5, wherein said C1-6 alkyl, C2-6 alkeny l, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalky l, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alky 1, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents.

82. The compound of any one of claims 1-80, or a pharmaceutically acceptable salt thereof, wherein each R5is independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalky l, C3-7 cycloalky 1, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa5, andNRc5Rd5, wherein said Ci-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONalkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents.

83. The compound of any one of claims 1-80, or a pharmaceutically acceptable salt thereof, wherein each R5is independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, ORa5, and NRc5Rd5, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, and 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents.

84. The compound of any one of claims 1-80, or a pharmaceutically acceptable salt thereof, wherein each R5is independently selected from D, halo, CN, C1-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa5. andNRc5Rd5, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalky 1, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents.

85. The compound of any one of claims 1-80, or a pharmaceutically acceptable salt thereof, wherein each R5is independently selected from D, halo, CN. C1-6 alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, ORa5, and NRc5Rd5, wherein said C1-6 alkyl, Ci-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalky l, 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R5Asubstituents.

86. The compound of any one of claims 1-80, or a pharmaceutically acceptable salt thereof, wherein each R5is independently selected from D, halo, CN, C1-6 alkyd, C1-6 haloalkyl, and ORa5, wherein said C1-6 alkyl and C1-6 haloalkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R5Asubstituents.

87. The compound of any one of claims 1-86, or a pharmaceutically acceptable salt thereof, wherein:each Ra5, Rc5. and Rd5is independently selected from H. C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R5Asubstituents;each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each R5Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)2NRc51Rd51, S(O)2Rb51, and S(O)2NRc51Rd51, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;each Ra51, Rc51, and Rd51is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;each Rb51is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;each R5Bis independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, C3-4 cycloalkyl, ORa52, SRa52, C(O)Rb52, C(O)NRc52Rd52, C(O)ORa52, OC(O)Rb52, OC(O)NRc52Rd52, NRc52Rd52, NRc52C(O)Rb52, NRc52C(O)ORa52, NRc52C(O)NRc52Rd52, NRc52S(O)2Rb52, NRc52S(O)2NRc52Rd52. S(O)2Rb52, and S(O)2NRc52Rd52;each Ra52, Rc52, and Rd52is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl; andeach Rb52is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

88. The compound of any one of claims 1-86, or a pharmaceutically acceptable salt thereof, wherein:each Ra5, Rc5, and Rd5is independently selected from H, Ci-6 alkyd, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each R5Ais independently selected from D, halo, CN, Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)2NRc51Rd51, S(O)2Rb51, and S(O)2NRc51Rd51, wherein said Ci-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONcycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1.4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R3Bsubstituents;each Ra51, Rc51, and Rd51is independently selected from H, C1-6alkyl, C1-6haloalkyl, and C3-7cycloalkyl; andeach Rb51is independently selected from C1-6 alkyl and C1-6 haloalkyl.

89. The compound of any one of claims 1-86, or a pharmaceutically acceptable salt thereof, wherein:each Ra5, Rc5. and Rd5is independently selected from H. C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyd-C 1-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyd, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Rb5is independently selected from C1-6 alky 1, C1-6 haloalky l, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl -Ci -4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyd, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each R5Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyd-C 1-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51. OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)2NRc51Rd51, S(O)2Rb51. and S(O)2NRc51Rd51, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R5Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach Ra51, Rc51, and Rd51is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; andeach Rb51is independently selected from C1-6alkyl and C1-6haloalkyl.

90. The compound of any one of claims 1-86, or a pharmaceutically acceptable salt thereof, wherein:each Ra3, Rc3, and Rd5is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R5Asubstituents;each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each R5Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51S(O)2Rb51, and NRc51S(O)2NRc51Rd51;each Ra51, Rc51, and Rd51is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, and C3-7 cycloalkyl; andeach Rb51is independently selected from Ci-6 alkyl and Ci-6 haloalkyl.

91. The compound of any one of claims 1-86, or a pharmaceutically acceptable salt thereof, wherein:each Ra3, Rc5, and Rd5is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONalkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Rb5is independently selected from C1-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each R5Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51S(O)2Rb51, and NRc51S(O)2NRc51Rd51;each Ra51, Rc51, and Rd51is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl; andeach Rb51is independently selected from C1-6 alkyl and C1-6 haloalkyl.

92. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: n is 1;p is 0, 1, 2, or 3;each m is independently 1 or 2;is 0 or S, and Z is CR1; oris CR2, and Z is O or S;X is O, S, S(O)2, S(O)NRc, or N(-L-R4);L is C(O), C(O)NRa, C(O)O, S(O), S(O)2, or S(O)2NRa;Raand Rcare each independently selected from H and C1-3 alky l;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONor, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring or 5-6 membered heteroaryl ring, each of which is optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;Ring moiety A is 5-9 membered heteroaryl;when Y is O, then R1is selected from H. D, CN. halo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7Cycloalkyl-Ci.4 alkyl, phenyl -C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORbl, SRbl, C(O)Rbl, C(O)NRclRdl, C(O)ORal, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)Rbl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl. S(O)2Rbl, and S(O)2NRclRdl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci 6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalk l. (R1A2)m-5-6 membered heteroaryl, (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl, (C3-7 cycloalkyl)-(R1A1)m-C1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd. 5-6 membered heteroaiyl-Ci-4 alkyl, ORbl, SRbl, C(O)Rbl, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl, and S(O)2Rbl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalky l portion of (R1A1)m-Ci.6haloalky l are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl. (ii) the C3-7 cy cl oalkyl-C 1-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl, and (iii) the C3-7 cycloalkyl-C1-4 alkyl portion of (C3-7 cycloalky l)-(R1A1)m-C 1-4 alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents;each Ral, Rcl. and Rdlis independently selected from H. C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R1Asubstituents;each Rblis independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each R1Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRc11Rd11, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Ral1, Rcl1, and Rdl1is independently selected from H, Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rbl1is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1Bis independently selected from halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRcl2Rd12, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12. S(O)2Rb12, and S(O)2NRcl2Rd12, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ral2, Rcl2, and Rdl2is independently selected from H, Ci-6 alky l, and C1-6 haloalkyl, wherein said Ci-6 alkyl and Ci-6 haloalkyl are each optionally substituted with 1. 2, 3, or 4 independently selected RGsubstituents;each Rbl2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each R1A1is independently selected from CN, C2-6 alkenyl, C2-6 alky nyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRc11Rd11, C(O)ORa11, OC(O)Rb11, OC(O)NRc11Rd11, NRc11Rd11, NRc11C(O)Rb11, NRc11C(O)ORa11, NRc11C(O)NRc11Rd11, NRc11S(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRc11Rd11, wherein said C2-6alkenyl, C2-6alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A2is independently selected from CN, NO2, (R1B)m-C1-6alkyl, C2-6alkenyl, C2-6alkynyl, Ci-6 haloalkyl, (R1B)m-C 1-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyd, phenyl-C 1-4 alky 1, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyd, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11. NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalky l, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONmembered heteroaryl-C 1.4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;each R1A3is independently selected from halo, OH, and C1-4alkoxy, wherein said C1-4alkoxy is optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents; and each R1A4is independently selected from halo, OH, C1-6alkyl, and C1-4alkoxy, wherein said C1-6alkyl and C1-4alkoxy are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rml1is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;R2is selected from H, D, halo, CN, CM alkyl, C haloalkyl, C3-4 cycloalkyl, C3-4 cycloalkyl-Ci-4 alkyl, ORb2, SRb2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2.OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2. NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said C1-6alkyl, C1-6haloalkyl, C3-4cycloalkyl, and C3-4cycloalkyl-C1-4alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents; each Ra2, Rc2, and Rd2is independently selected from H, C1-6alkyl, and C1-6haloalkyl; each Rb2is independently selected from C1-6alkyl and C1-6haloalkyl; each R3is independently selected from halo, CN, C1-6alkyl, C1-6haloalkyl, ORa3, and NRc3Rd3, wherein said C1-6alkyl and C1-6haloalkyl, and C3-4cycloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents; each Ra3, Rc3, and Rd3is independently selected from H, C1-6alkyl, and C1-6haloalkyl; R4is selected from H, C1-6alkyl, C1-6haloalkyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl, wherein said C1-6alkyl, C1-6haloalkyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;each R4Ais independently selected from oxo, D, halo, CN, C1-6alkyl, C1-6haloalkyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONcycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41, NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each R4Bis independently selected from D, halo, CN, C1-6alkyl, C1-6haloalkyl, and C3-4cycloalkyl, ORa42, SRa42, C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alky l, and Ci-6 haloalkyl;each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;each R5is independently selected from D, halo, CN, Ci-6 alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa3, SRa3, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONNRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5. S(O)2Rb5, and S(O)2NRc5Rd5, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Ra3, Rc3, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C 3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky I-C1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R5Asubstituents;each Rb5is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each R5Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, ORa51, SRa51, C(O)Rb51. C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51. OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)2NRc51Rd51, S(O)2Rb51, and S(O)2NRc51Rd51, wherein said C1-6 alkyd, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;each Ra51, Rc51, and Rd51is independently selected from H, Ci-6 alky l, C1-6 haloalky l, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, ph enyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaiy I-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;each Rb51is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;each R5Bis independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa52, SRa52, C(O)Rb52, C(O)NRc52Rd52, C(O)ORa52, OC(O)Rb52, OC(O)NRc52Rd52, NRc52Rd52, NRc52C(O)Rb52, NRc52C(O)ORa52, NRc52C(O)NRc52Rd52, NRc52S(O)2Rb52, NRc52S(O)2NRc52Rd52, S(O)2Rb52, and S(O)2NRc52Rd52;each Ra52, Rc52, and Rd52is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;each Rb52is independently selected from C1-6 alkyl and C1-6 haloalkyl; and each RGis independently selected from OH, NO2, CN, halo. C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalkyl, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxy carbonylamino, C1-3 alkylaminocarbonyloxy. C1-3 alkylsulfonylamino, aminosulfonyl, C 1-3 alkylaminosulfonyl, di(Ci-3 alkyl )aminosulfonyl, aminosulfonylamino, C1-3 alkydaminosulfonylamino, di(C 1-3 alkyl)aminosulfonyl amino, aminocarbonylamino, C1-3 alky laminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino.

93. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: n is 1;p is 0, 1, 2, or 3;each m is independently 1 or 2;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONY is O or S, and Z is CR1; or, Y is CR2, and Z is O or S;X is O, S, S(O)2, S(O)NRc, or N(-L-R4);L is C(O), C(O)O, S(O)2, or S(O)2NRa;Raand Rcare each independently selected from H and C1-3 alkyl;Ring moiety A is 5-9 membered heteroaryl;when Y is O, then R1is selected from H, D, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORbl, SRbl, C(O)Rbl, C(O)NRclRdl, C(O)ORal, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)Rbl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl, S(O)2Rbl, and S(O)2NRclRdl, wherein said C1-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci-6 haloalkyl. C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkvl. (R1A2)m-5-6 membered heteroary l, (R1A)m-C.-7 cycloalkyl-C 1-4 alkyl, (C3-7 cycloalky l)-(R1A1)m-C1-4 alkyd, phenyl-Ci-4 alky l, 4-7 membered heterocycloalky 1-C 1-4 alkyd, 5-6 membered heteroaiyl-C 1.4 alkyl, ORbl, SRbl, C(O)Rbl, OC(O)Rbl, OC(O)NRclRdl, NRclRdl, NRclC(O)ORal, NRclC(O)NRclRdl, NRclS(O)2Rbl, NRclS(O)2NRclRdl. and S(O)2Rbl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyd, and 5-6 membered heteroaryd-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONalkyl and (ii) the C1-6haloalkyl portion of (R1A1)m-C1-6haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, (ii) the C3-7 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-Ci-4 alky l, and (iii) the C3-7 cycloalky 1-C1-4 alkyl portion of (C3-7 cycloalkyl)-(R1A1)m-Ci-4 alkyl are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents:each Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2. 3, or 4 independently selected R1Asubstituents;each Rblis independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each R1Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11. OC(O)NRcllRd11, NRcllRd11, NRc11C(O)Rb11, NRc11C(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcl1Rd11, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Ral1, Rcl1, and Rdl1is independently selected from H, Ci-6 alky l, C1-6 haloalky l, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, ph enyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaiy 1-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rbl1is independently selected from Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1Bis independently selected from halo, CN, NO2, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRcl2Rd12, NRcl2C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12, S(O)2Rb12, and S(O)2NRcl2Rd12, wherein said C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ral2, Rcl2, and Rdl2is independently selected from H, C1-6 alkyd, and C1-6 haloalkyl, wherein said Ci-6 alkyl and C1-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Rbl2is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy. (R1B)m-C3-7 cycloalky 1. phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, pheny 1-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaiy I-C1.4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRc11Rd11. wherein said C2-6 alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaiyl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A2is independently selected from CN, NO2, (R1B)m-Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheterocycloalkyL 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1.4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRc11S(O)2NRc11Rd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6alkenyl, C2-6alkynyl, C1-6 haloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1.4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A3is independently selected from halo. OH, and C1-4 alkoxy, wherein said C1.4 alkoxy is optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents; and each R1A4is independently selected from halo, OH, Ci-6 alkyl, and CM alkoxy, wherein said C1-6 alkyl and C 1-4 alkoxy are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rm11is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;R2is selected from H, D, halo, CN, Ci-6 alkyl, C1-6 haloalkyl, C3-4 cycloalkyl, C3-4 cycloalkyl-C 1.4 alkyl, ORb2, SRb2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said C1-6alkyl, C1-6haloalkyl, C3-4 cycloalkyl, and C3-4 cycloalkyl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each Ra2, Rc2, and Rd2is independently selected from H, Ci-6 alky l, and Ci-6 haloalkyl; each Rb2is independently selected from Ci-6 alky l and Ci-6 haloalkyl;each R3is independently selected from halo. CN, Ci-6 alkyl. C 1-6 haloalkyl, ORa3, and NRc3Rd3, wherein said Ci-6 alkyl and Ci-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1 or 2 independently selected RGsubstituents;each Ra3, Rc3, and Rd3is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; R4is selected from H, Ci-6 alkyl. Ci-6 haloalkyl, C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalkyL 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONalkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, ph enyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaiy 1-C 1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;each R4Ais independently selected from D, halo, CN, C1-6 alkyl, Ci-6 haloalkyl. C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaiy 1, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaiy 1-C 1.4 alkyl, ORa41, SRa41, C(O)Rb41, C(O)NRc41Rd41, C(O)ORa41, OC(O)Rb41, OC(O)NRc41Rd41, NRc41Rd41, NRc41C(O)Rb41. NRc41C(O)ORa41, NRc41C(O)NRc41Rd41, NRc41S(O)2Rb41, NRc41S(O)2NRc41Rd41, S(O)2Rb41, and S(O)2NRc41Rd41, wherein said Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalky 1-C 1-4 alkyd, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaiy 1-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alky 4, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalky l, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 Cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4 alky l are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Rb41is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaiy 1-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, and C3-4 cycloalkyl, ORa42, SRa42, C(O)Rb42, C(O)NRc42Rd42, C(O)ORa42, OC(O)Rb42, OC(O)NRc42Rd42, NRc42Rd42, NRc42C(O)Rb42, NRc42C(O)ORa42, NRc42C(O)NRc42Rd42, NRc42S(O)2Rb42, NRc42S(O)2NRc42Rd42, S(O)2Rb42, and S(O)2NRc42Rd42;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;each R5is independently selected from D, halo, CN, Ci-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl -C 1-4 alkyl, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5, wherein said C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1.4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Ra5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alky l, 4-7 membered heterocycloalkyl-C 1-4 alky l, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Rb5is independently selected from C1-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each R5Ais independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51. OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51C(O)ORa51, NRc51C(O)NRc51Rd51, NRc51S(O)2Rb51, NRc51S(O)2NRc51Rd51, S(O)2Rb51,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONand S(O)2NRc51Rd51, wherein said Ci-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;each Ra51, Rc51. and Rd51is independently selected from H, Ci-6 alkyl. C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;each Rb51is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci.4 alkyl, 4-7 membered heterocycloalky I-C1.4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Bsubstituents;each R5Bis independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa52, SRa52, C(O)Rb52, C(O)NRc52Rd52, C(O)ORa52, OC(O)Rb52, OC(O)NRc52Rd52, NRc52Rd52, NRc52C(O)Rb52, NRc52C(O)ORa52, NRc52C(O)NRc52Rd52, NRc52S(O)2Rb52, NRc52S(O)2NRc52Rd52, S(O)2Rb52, and S(O)2NRc52Rd52;each Ra52, Rc52, and Rd52is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb52is independently selected from Ci-6 alkyl and Ci-6 haloalkyl; and each RGis independently selected from OH, NO2, CN, halo, C1-3 alky l, C2-3 alkenyl, C2-3 alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alky l, C3-4 cycloalkyl. C1-3 alkoxy, C1.3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino. thio, Ci-3 alkydthio, C1-3 alkylsulfinyl, C1.3 alkylsulfonyl, carbamyl, C1.3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkyd carbonyl, C1-3 alkoxy carbonyl, C1-3 alkylcarbonyloxy, C1-3 alky dcarbonydamino, C1-3 alkoxy carbonylamino, C1-3 alkydaminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C 1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONaminosulfonydamino, C1-3 alkylaminosulfonylamino, di(C1-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alky laminocarbonylamino, and di(Ci-3 alky l)aminocarbonyl amino.

94. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: n is 1;p is 0, 1, 2, or 3;each m is independently 1 or 2;, Y is O or S, and Z is CR1; orz, Y is CR2, and Z is O or S;X is O, S(O)2, or N(-L-R4);L is C(O), C(O)NRa, C(O)O, S(O), S(O)2, or S(O)2NRa;Rais selected from H and C 1-3 alky l;or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring optionally substituted by 1. 2, or 3 independently selected R4Asubstituents;Ring moiety A is 5-9 membered heteroaryl;when Y is O, then R1is selected from H, D, CN, halo, C1-6 alkyd, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl -C 1-4 alkyl, ORbl, SRbl, and NRclRdl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alky nyl, C1-6 haloalky l, C3-7 cycloalkyd, phenyl, 4-7 membered heterocycloalky l, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyd, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci-6 haloalky 1, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalky 1, pheny l, 4-7 membered heterocycloalkyd, (R1A2)m-5-6 membered heteroaryl, (R1A)m-C3-7 cycloalkyd-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONmembered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl. ORb1, SRb1, and NRc1Rd1, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-Ci.6haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, and (ii) the C3-7 cycloalkyl-Ci-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl are each optionally substituted by 1, 2. or 3 independently selected R1A4substituents;each Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalky I-C1-4 alkyl, phenyl-C 1-4 alky l, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each Rb1is independently selected from C1-6 alkyl, C1-6 haloalkyl. C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each R1Ais independently selected from halo, CN. C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11. OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONmembered heteroaryl-C 1.4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;each Ral1, Rcl1, and Rdl1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rbl1is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1Bis independently selected from halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRc12Rd12, NRc12C(O)Rb12, NRcl2C(O)ORa12, NRcl2C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12. S(O)2Rb12, and S(O)2NRcl2Rd12;each Ral2, Rcl2, and Rdl2is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;each Rbl2is independently selected from C1-6 alkyl and C1-6 haloalkyl;each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NR011Rd11. NRc11C(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11. wherein said C2-6alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach R1A2is independently selected from CN, NO2, (R1B)m-C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, (R1B)m-C1-4alkoxy, (R1B)m-C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRollRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11.NRcllS(O)2NRcllRdllS(O)2Rb11, and S(O)2NRcl1Rd11, wherein said C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalky l, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;each R1A3is independently selected from halo, OH, and C1-4alkoxy; andeach R1A4is independently selected from halo, OH, C1-6 alkyl, and CM alkoxy; each Rml1is independently selected from C2-6 alkenyl. C2-6 alkynyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl;R2is selected from H, halo, CN, Ci-6 alkyl, and Ci-6 haloalkyl, wherein said CM alkyl and C1-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each R3is independently selected from Ci-6 alkyl, Ci-6alkylene-ORa3. C1-6 alkylene-NRc3Rd3, ORa3, and NRc3Rd3;each Ra3, Rc3, and Rd3is independently selected from H, C1-6alkyl, and C1-6haloalkyl; R4is selected from H, C1-6alkyl, C1-6haloalkyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C3-10cycloalkyl-C1-4alkyl, wherein said C1-6alkyl, C1-6haloalkyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C3-10cycloalkyl-C1-4alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;each R4Ais independently selected from oxo, D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa41, and NRc41Rd41, wherein said C1-6alkyl, C1-6haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONmembered heteroaryl-C 1.4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R4Bsubstituents;each Ra41, Rc41, and Rd41is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;each Rb41is independently selected from C1-6 alkyl and C1-6 haloalkyl, which are each optionally substituted with 1 or 2 independently selected R4Dsubstituents;each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa42and NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alky l, and C1-6 haloalkyl;each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;each R5is independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, ORa5, and NRc5Rd5, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, and 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Ra5, Rc5, and Rd5is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C1-4alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Rb5is independently selected from C1-6alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each R5Ais independently selected from D, halo, CN, Ci-6 alky l, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, ORa51, SRa51,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONC(O)Rb51, C(O)NRc51Rd51, C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51, NRc51Rd51, NRc51C(O)Rb51, NRc51S(O)2Rb51, and NRc51S(O)2NRc51Rd51;each Ra51, Rc51, and Rd51is independently selected from H, C1-6 alkyd, C1-6 haloalkyl, and C3-7 cycloalky 1;each Rb51is independently selected from C1-6 alkyl and C1-6 haloalkyl; and each RGis independently selected from OH, NO2, CN, halo, C1-3alkyl, C2-3alkenyl, C2-3alkynyl, C1-3 haloalkyl, cyano-Ci-3 alkyl, HO-C1-3 alkyl, C1-3 alkoxy-Ci-3 alkyl, C3-4 cycloalky l, C1-3 alkoxy, C1-3 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, Ci-3 alkylthio, C1-3alkylsulfinyl, C1-3alkylsulfonyl, carbamyl, C1-3alkylcarbamyl, di(C1-3alkyl)carbamyl, carboxy, C1-3alkylcarbonyl, C1-3alkoxycarbonyl, C1-3alkylcarbonyloxy, C1-3alkylcarbonylamino, C1-3alkoxycarbonylamino, C1-3alkylaminocarbonyloxy, C1-3alkylsulfonylamino, aminosulfonyl, C1-3alkylaminosulfonyl, di(C1-3alkyl)aminosulfonyl, aminosulfonylamino, C1-3alkylaminosulfonylamino, di(C1-3alkyl)aminosulfonylamino, aminocarbonylamino, C1-3alkylaminocarbonylamino, and di(C1-3alkyl)aminocarbonylamino.

95. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: n is 1;p is 0, 1, 2, or 3;each m is independently 1 or 2;ZY is O or S, and Z is CR1; or, Y is CR2, and Z is O or S;X is O, S(O)2, or N(-L-R4);L is C(O), C(O)O, S(O)2, or S(O)2NRa;Rais selected from H and C1-3 alkyl;Ring moiety A is 5-9 membered heteroaryl;when Y is O, then R1is selected from H, D, CN, halo, C1-6 alky l, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONmembered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORbl, SRbl, and NRclRdl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl. C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1. 2, 3, or 4 independently selected R1Asubstituents;when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci.6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl, (R1A)m-C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl. ORb1, SRb1, and NRc1Rd1, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alky l, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-Ci-6 haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, and (ii) the C3-7 cycloalkyl-Ci-4 alkyl portion of (R1 A)m-C3-7 cycloalkyl-Ci-4 alkyl are each optionally substituted by 1, 2. or 3 independently selected R1A4substituents;each Ra1, Rc1, and Rd1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each Rb1is independently selected from C1-6 alkyl, C1-6 haloalkyl. C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach R1Ais independently selected from halo, CN. Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11. OC(O)NRcllRd11, NRcllRd11, NRc11C(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rh11, NRcllS(O)2NRcllRd11, S(O)2Rb11. and S(O)2NRcl1Rd11, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3. or 4 independently selected R1Bsubstituents;each Ral1, Rcl1, and Rdl1is independently selected from H, C1-6 alkyd, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalky 1, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaiy 1-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rbl1is independently selected from Ci-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C1-4 alkyl, phenyl-C1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1Bis independently selected from halo, CN, NO2, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, C3-4 cycloalkyl, ORa12, C(O)Rb12, C(O)NRc12Rd12, C(O)ORa12, OC(O)Rb12, OC(O)NRc12Rd12, NRc12Rd12, NRc12C(O)Rb12, NRc12C(O)ORa12, NRc12C(O)NRc12Rd12, NRcl2S(O)2Rb12, NRcl2S(O)2NRcl2Rd12. S(O)2Rb12, and S(O)2NRcl2Rd12;each Ra12, Rc12, and Rd12is independently selected from H, C1-6alkyl, and C1-6haloalkyl;each Rbl2is independently selected from C1-6alkyl and C1-6haloalkyl;each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRdn, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcllRd11, wherein said C2-6alkenyl, C2-6alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A2is independently selected from CN, NO2, (R1B)m-C1-6alkyl, C2-6alkenyl, C2-6alkynyl, Ci-6 haloalkyl. (R1B)m-C 1-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORm11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11.NRc11S(O)2NRc11Rd11, S(O)2Rb11. and S(O)2NRcllRd11, wherein said C2-6alkenyl, C2-6alkynyl, C1-6 haloalkyl. phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A3is independently selected from halo, OH, and C1-4 alkoxy; andeach R1A4is independently selected from halo, OH, Ci-6 alkyl, and C1-4 alkoxy; each Rm11is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl;R2is selected from H, halo, CN, C1-6 alkyl, and C1-6 haloalkyl, wherein said C1-6 alkyl and C1-6 haloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents;each R3is independently selected from C1-6alkyl, C1-6alkylene-ORa3, C1-6alkylene-NRc3Rd3, ORa3, and NRc3Rd3;each Ra3, Rc3, and Rd3is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl; R4is selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein said Ci-6 alky l, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheteroaryl are each optionally substituted by 1, 2, 3. or 4 independently selected R4Asubstituents;each R4Ais independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa41, and NRc41Rd41, wherein said Ci-6 alkyl. C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cy cl oalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each Ra41, Rc41, and Rd41is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each Rb41is independently selected from Ci-6 alkyl and Ci-6 haloalkyl, which are each optionally substituted with 1 or 2 independently selected R4Bsubstituents;each R4Bis independently selected from D, halo, CN, Ci-6 alkyl, Ci-6 haloalkyl, ORa42and NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;each Rb42is independently selected from Ci-6 alkyl and Ci-6 haloalkyl;each R5is independently selected from D, halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa5, and NRc5Rd5, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalky l, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Ra5, Rc5, and Rd5is independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroary l, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alky 1, 4-7 membered heterocycloalky 1-C 1-4 alky 1, and 5-6 membered heteroary 1-C 1-4 alky l, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Rb5is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl,Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONC3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each R5Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, ORa51, SRa51, C(O)Rb51, C(O)NRc51Rd51. C(O)ORa51, OC(O)Rb51, OC(O)NRc51Rd51. NRc51Rd51, NRc51C(O)Rb51, NRc51S(O)2Rb51, and NRc51S(O)2NRc51Rd51;each Ra51, Rc51, and Rd51is independently selected from H, Ci-6 alky l, and C1-6 haloalkyl;each Rb51is independently selected from C1-6 alkyl and C1-6 haloalkyl; and each RGis independently selected from OH, NO2, CN, halo, C1-3alkyl, C2-3alkenyl, C2-3alkynyl, C1-3haloalkyl, cyano-C1-3alkyl, HO-C1-3alkyl, C1-3alkoxy-C1-3alkyl, C3-4cycloalkyl, C1-3alkoxy, C1-3haloalkoxy, amino, C1-3alkylamino, di(C1-3alkyl)amino, thio, C1-3alkylthio, C1-3alkylsulfinyl, C1-3alkylsulfonyl, carbamyl, C1-3alkylcarbamyl, di(C1-3alkyl)carbamyl, carboxy, C1-3alkylcarbonyl, C1-3alkoxycarbonyl, C1-3alkylcarbonyloxy, C1-3alkylcarbonylamino, C1-3alkoxycarbonylamino, C1-3alkylaminocarbonyloxy, C1-3alkylsulfonylamino, aminosulfonyl, C1-3alkylaminosulfonyl, di(C1-3alkyl)aminosulfonyl, aminosulfonylamino, C1-3alkylaminosulfonylamino, di(C1-3alkyl)aminosulfonylamino, aminocarbonylamino, C1-3alkylaminocarbonylamino, and di(C1-3alkyl)aminocarbonylamino.

96. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: n is 1;p is 0, 1, 2, or 3;each m is independently 1 or 2;Y is O or S, and Z is CR1; or, Y is CR2, and Z is O or S;X is O, S(O)2, or N(-L-R4);Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONL is C(O), C(O)NRa, C(O)O. S(O), S(O)2, or S(O)2NRa;Raand Rcare each independently selected from H and C1-3 alkyl;or, alternatively, Raand R4, taken together with the nitrogen atom to which they are attached, form a 4-7 membered heterocycloalkyl ring optionally substituted by 1 or 2 independently selected R4Asubstituents;Ring moiety A is 5-9 membered heteroaryl;when Y is O, then R1is selected from H, D, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, and ORbl; wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl. 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;when Y is S, then R1is selected from H, D, halo, (R1A1)m-C1-6alkyl, (R1A1)m-C1-6haloalkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, (R1A2)m-5-6 membered heteroaryl, (R1A)m-C3-7cycloalkyl-C1-4alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, 5-6 membered heteroaryl-C1-4alkyl, and ORb1, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R1A1)m-Ci-6 haloalkyl are each optionally substituted by 1, 2, or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, and (ii) the C3-7 cycloalkyl-C 1-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-C 1-4 alky l are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents;each Ra1, Rc1, and Rd1is independently selected from H, C1-6alkyl, C1-6haloalkyl, C2-6alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C1-4alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6haloalkyl, C3-7cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-C1-4alkyl, phenyl-C 1-4 alkyl, 4-7 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each Rblis independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each R1Ais independently selected from halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa11, SRa11, C(O)Rb11, C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcl1Rd11, wherein said C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Ra11, Rc11, and Rd11is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyd, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalky 1-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rbl1is independently selected from Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alky l, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1Bis independently selected from halo, CN. Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa12, and NRcl2Rd12;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach Ral2, Rcl2, and Rdl2is independently selected from H, Ci-6 alkyl, and Ci-6 haloalkyl;each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl. ORm11. andNRcllRd11. wherein said C2-6 alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C1-4alkyl, and 5-6 membered heteroaryl-C1-4alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A2is independently selected from CN, NO2, (R1B)m-Ci-6 alkyl. C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, (R1B)m-Ci-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORm11and NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C1-4 alkyl, and 5-6 membered heteroaryd-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A3is independently selected from halo, OH, and C1-4 alkoxy; andeach R1A4is independently selected from halo, OH, C1-6 alkyl, and C1-4 alkoxy; each Rml1is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl;R2is selected from H, halo, CN, C1-4 alkyl, and C1-4 haloalkyl;each R3is independently selected from C1-6 alkyl, C1-6 alkylene-OH and OH;R4is selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C3-7 cycloalkyl-C1-4 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and C3-7 cycloalkyl-C1-4 alkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;each R4Ais independently selected from oxo, halo, CN, C1-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each R4Bis independently selected from D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, ORa42and NRc42Rd42;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONeach Ra42, Rc42, and Rd42is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;each R5is independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalky l, 4-7 membered heterocycloalky 1-C 1-4 alkyl, ORa5, and NRc5Rd5, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, 4-7 membered heterocycloalkyl, and 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Ra5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl. C3-7 cycloalkyl-C 1-4 alkyl, and 4-7 membered heterocycloalkyl-Ci-4 alkyl, wherein said C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalkyl-C 1-4 alky 1, and 4-7 membered heterocycloalkyl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each R5Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, 4-7 membered heterocycloalkyl, ORa51, and NRc51Rd51; andeach Ra51, Rc51, and Rd51is independently selected from H, C1-6 alkyd, C1-6 haloalkyl, and C3-7 cycloalkyl.

97. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: n is 1;p is 0, 1, 2, or 3;each m is independently 1 or 2;Y is O or S, and Z is CR1; orZ, Y is CR2, and Z is O or S;X is O, S(O)2, or N(-L-R4);L is C(O), C(O)O, S(O)2, or S(O)2NRa;Raand Rcare each independently selected from H and C1-3 alkyl;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONRing moiety A is 5-9 membered heteroaryl;when Y is 0, then R1is selected from H, D, CN, halo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, and ORbl; wherein said C1-6 alkyl, C2-6 alkenyl. C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;when Y is S, then R1is selected from H, D, halo, (R1A1)m-Ci-6 alkyl, (R1A1)m-Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalk l. (R1A2)m-5-6 membered heteroaryl, (R1A)m-C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyd, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, and ORbl, wherein said C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci.4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; wherein (i) the C1-6 alkyl portion of said (R1A1)m-Ci-6 alkyl and (ii) the C1-6 haloalkyl portion of (R, A,)m-Ci-6 haloalkyl are each optionally substituted by 1, 2. or 3 independently selected R1A3substituents; and wherein (i) the 5-6 membered heteroaryl portion of said (R1A2)m-5-6 membered heteroaryl, and (ii) the C3-7 cycloalkyl-C 1-4 alkyl portion of (R1A)m-C3-7 cycloalkyl-Ci-4 alkyd are each optionally substituted by 1, 2, or 3 independently selected R1A4substituents;each Ral, Rcl. and Rdlis independently selected from H. C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyd, and 5-6 membered heteroaryl-C 1-4 alkyd, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl. phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each Rblis independently selected from C1-6 alky 1, Ci-6 haloalky l, C2-6 alkeny l, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION6 membered heteroaryl-Ci-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents;each R1Ais independently selected from halo, CN, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-Ci-4 alkyl, ORa11. SRa11, C(O)Rb11. C(O)NRcllRd11, C(O)ORa11, OC(O)Rb11, OC(O)NRcllRd11, NRcllRd11, NRcllC(O)Rb11, NRcllC(O)ORa11, NRcllC(O)NRcllRd11, NRcllS(O)2Rb11, NRcllS(O)2NRcllRd11, S(O)2Rb11, and S(O)2NRcl1Rd11, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl. 4-7 membered heterocycloalkyl. 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Ral1, Rcl1, and Rdl1is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7cycloalkyl-Ci-4 alkyl, phenyl-C 1-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each Rbl1is independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl, which are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1Bis independently selected from halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-4 cycloalkyl, ORa12. and NRcl2Rd12;each Ral2, Rcl2, and Rdl2is independently selected from H, Ci-6 alkyl, and C1-6 haloalkyl;each R1A1is independently selected from CN, C2-6alkenyl, C2-6alkynyl, (R1B)m-Ci-4 alkoxy. (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, 5-6 memberedAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONheteroaryl-C 1-4 alkyl. ORm11. andNRcllRd11. wherein said C2-6 alkenyl, C2-6 alkynyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-Ci-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A2is independently selected from CN, NO2, (R1B)m-Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl. (R1B)m-C1-4 alkoxy, (R1B)m-C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl-C 1-4 alkyl, ORm11and NRcllRd11, wherein said C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalky l, phenyl. 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-C 1-4 alkyl, phenyl-Ci-4 alkyl, 4-7 membered heterocycloalkyl-Ci-4 alkyl, and 5-6 membered heteroaryl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents;each R1A3is independently selected from halo, OH, and C1-4 alkoxy; andeach R1A4is independently selected from halo. OH, Ci-6 alkyl, and C1-4 alkoxy; each Rml1is independently selected from C2-6 alkenyl, C2-6 alkynyl, C3-5 cycloalkyl, and 4-5 membered heterocycloalkyl;R2is selected from H, halo, CN, Ci-6 alkyd, and Ci-6 haloalkyl;each R3is independently selected from C1-6 alkylene-OH and OH;R4is selected from H, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein said C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 independently selected R4Asubstituents;each R4Ais independently selected from halo, CN, C1-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R4Bsubstituents;each R4Bis independently selected from D, halo, CN, C1-6 alkyl, C1-6 haloalkyl, ORa42and NRc42Rd42;each Ra42, Rc42, and Rd42is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl;each R5is independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 haloalkyl, C3-4 cycloalkyl, ORa5, andNRc5Rd5, wherein said Ci-6 alkyl, C2-6Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONalkenyl, C2-6 alkynyl, Ci-6 haloalky I. and C3-4 cycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each Ra5, Rc5, and Rd5is independently selected from H, Ci-6 alkyd, Ci-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalkyl-C 1-4 alkyl, and 4-7 membered heterocycloalkyl-C 1-4 alkyl, wherein said C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C3-7 cycloalkyl-Ci-4 alkyl, and 4-7 membered heterocycloalkyl-C 1-4 alkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R5Asubstituents;each R5Ais independently selected from D, halo, CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, ORa51, and NRc51Rd51; andeach Ra51, Rc51. and Rd51is independently selected from H, Ci-6 alkyd, and C1-6 haloalkyl.

98. The compound of any one of claims 1-43, 48-49, and 56-97, wherein the compound is a compound of Formula (II):or a pharmaceutically acceptable salt thereof.

99. The compound of any one of claims 1-40, 44-49, and 56-97, wherein the compound is a compound of Formula (III):or a pharmaceutically acceptable salt thereof.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION100. The compound of any one of claims 1-40 and 50-97, wherein the compound is a compound of Formula (IV):or a pharmaceutically acceptable salt thereof.

101. The compound of any one of claims 1-40 and 50-97, wherein the compound is a compound of Formula (V):or a pharmaceutically acceptable salt thereof.

102. The compound of claim 1, wherein the compound is selected from:(3,4R)-4-((6-(17 / -pyrazol-4-yl)thieno[3,2-< / ]pyrimidin-2-yl)arnino)-l-(methylsulfonyl)piperidin-3-ol;(37?,47?)-4-((6-(3-methyl-177-pyrazol-4-yl)thieno[3,2-< / |pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;(37?,4A)-4-((6-(177-pyrazol-4-yl)thieno[3,2-< / |pyrimidin-2-yl)amino)-l-(cyclopropylsulfonyl)piperidin-3-ol;(37?,47?)-4-((6-(177-pyrazol-4-yl)thieno[2,3-<7]pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;(3?,4 )-4-((6-(17 -pyrazol-4-yl)thieno[3,2-t / ]pyrimidin-2-yl)amino)-l-((l-methyl-17 / -pyrazol-4-yl)sulfonyl)piperidin-3-ol;(3A,47?)-4-((6-(l / / -pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)-l-((l-methyl-17 / -pyrazol-3-yl)sulfonyl)piperidin-3-ol;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONl-((3?,4?)-3-hydroxy-4-((6-(pyridazin-4-yl)thieno[3,2-tZ]pyrimidin-2-yl)amino) piperidin- 1 -y l)ethan- 1 -one;(3S,47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-< ]pyrirnidin-2-yl)arnino)tetrahydro-27f-pyran-3-ol;(3S,47?)-4-((7-(4-(azetidin-l-ylmethyl)-3-fluorophenyl)-6-(177-pyrazol-4-yl)thieno[3,2-<7|pyrimidin-2-yl)amino)tetrahydro-277-pyran-3-ol;(35',47?)-4-((7-(2-((isopropylamino)methyl)pyridin-4-yl)-6-(l / / -pyrazol-4-yl)thieno[3,2-<7|pyrimidin-2-yl)amino)tetrahydro-277-pyran-3-ol;(3S.47?)-4-((6-(177-pyrazol-4-yl)-7-(((S)-pyrrolidin-2-yl)ethynyl)thieno[3,2-t / |pyrimi din-2 -yl)amino)tetrahydro-277-pyran-3-ol;(3S,47?)-4-((6-(177-pyrazol-4-yl)-7-(pyridin-4-ylethynyl)thieno[3,2-t / ]pyrirni din-2-yl)ammo)tetrahydro-27 / -pyrari-3-ol:(3S,47?)-4-((7-(azetidin-3-yl)-6-(177-pyrazol-4-yl)thieno[3,2-< / ]pyrimi din-2-yl)amino)tetrahydro-277-pyran-3-ol;(35,47?)-4-((6-(17 / -pyrazol-4-yl)-7-(((?)-pyrrolidin-3-yl)methyl)thieno[3,2-c / |pyrimi din-2 -yl)amino)tetrahydro-277-pyran-3-ol;(37?, 47?)-4-((6-(177-pyrazol-4-yl)furo[3,2-< / ]pyrimi din-2 -yl)amino)-l-(methylsulfonyl)piperidin-3-ol;(37?,4?)-l-(methylsulfonyl)-4-((6-(pyridin-4-yl)thieno[3,2-< / |pyrimidin-2-yl)amino)piperidin-3-ol;(3?,4?)-l-(methylsulfonyl)-4-((6-(thiazol-5-yl)thieno[3,2-< ]pyrirnidin-2-y l)amino)piperi din-3 -ol;(37?,47?)-4-((6-(3-(difluoromethyl)-177-pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;methyl (37?,47?)-4-((6-(3-(azetidin-3-ylmethoxy)-177-pyrazol-4-yl)thieno[3,2-<7|pyrimidin-2-yl)amino)-3-hydroxypiperidine-l -carboxylate;(3S.47?)-4-((7-ethoxy-6-(177-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)tetrahydro-277-pyran-3-ol;(3S,47?)-4-((7-(2-(dimethylamino)ethoxy)-6-(17 / -pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)tetrahydro-277-pyran-3-ol;ethyl (37?,47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-c / ]pyrimidin-2-yl)amino)-3-hy droxypiperidine- 1 -carboxylate;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION((37?,47?)-4-((6-(127-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)(cyclopropyl)methanone;(3J?,4J?)-3-hydroxy-jV,jV-dimethyl-4-((6-(6-methyl-17 / -indazol-5-yl)thieno[2,3-<7|pyrimidin-2-yl)amino)piperidine-l -sulfonamide;cyclopropyl((3J?,47?)-4-((6-(6-fluoro-5-hydroxy-3-methylpyridin-2-yl)thieno[2,3-<7]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)methanone;cyclopropyl((37?,47?)-4-((6-(3-((dimethylamino)methyl)-177-pyrazol-4-yl)thieno[3,2-c / |pyrimidin-2-yl)amirio)-3-hydroxypiperidin-l-yl)metharione: and(35',4J?)-4-((7-(4-isopropylpiperazin-l-yl)-6-(177-pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)tetrahydro-277-pyran-3-ol;or a pharmaceutically acceptable salt thereof.

103. The compound of claim 1, wherein the compound is selected from:(37?,47?)-4-((6-(l-methyl-177-pyrazol-4-yl)thieno[3,2-< / |pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;(3R, 47?)-4-((6-(3-fluoro-17f-pyrazol-4-yl)thieno[3,2-<7]pyrimi din-2 -yl)amino)-l-(methylsulfonyl)piperidin-3-ol;(37?,47?)-4-((6-(3-methoxy-l / 7-pyrazol-4-yl)thieno[3,2-cil|pyrimidin-2-yl)amino)-l-(methy Isulfony l)pi p eri din-3 -ol;(37?,47?)-4-((6-(3-cyclopropyl-12f-pyrazol-4-yl)thieno[3,2-<7]pyrimi din-2 -yl)amino)-l-(methylsulfonyl)piperidin-3-ol;(37?,47?)-4-((6-(3-isopropyl-177-pyrazol-4-yl)thieno[3,2-<7|pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;(3,47 )-4-((6-(3-ethyl-lH-pyrazol-4-yl)thieno[3,2-t / ]pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;(3?,4?)-l-(methylsulfonyl)-4-((6-(pyridazin-4-yl)thieno[3,2-J]pyrimidin-2-yl)amino)piperidin-3-ol;(37?,4?)-l-(methylsulfonyl)-4-((6-(pyridin-3-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)piperidin-3-ol;(3 / .4 / )-4-((6-(isothiazol-4-yl)thieno|3.2- / |pyrimidin-2-yl)ammo)-l -(methylsulfonyl)piperidin-3-ol;((37?, 47?)-4-((6-(12 / -pyrazol-4-yl)thieno[3,2-< / ]pyrimi din-2 -yl)amino)-3-hydroxypiperidin-l-yl)(l-methylcyclopropyl)methanone;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION((3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)(1-(trifluoromethyl)cyclopropyl)methanone;1-((3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)butan-1-one;1-((3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)ethan-1-one;methyl (3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidine-1-carboxylate;((3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)(1-(difluoromethyl)cyclopropyl)methanone;1-((3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)-4,4,4-trifluorobutan-1-one;1 -((37?, 47?)-4-((6-(177-pyrazol-4-yl)thieno[3,2-<7|pyrimi din-2 -yl)amino)-3-hy droxypiperidin- 1 -yl)-2-methy Ipropan- 1 -one;((3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)(cyclobutyl)methanone;((3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)(1-methylcyclobutyl)methanone;((3R,4R)-4-((6-(lH-pyrazol-4-yl)thieno[3.2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperidin-l-yl)(l-fluorocyclobutyl)methanone;(3R,4R)-4-((6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-l- (ethylsulfonyl)piperidin-3-ol;((3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)(1-(1,1-difluoroethyl)cyclopropyl)methanone;((3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)((1S,2R)-2-fluorocyclopropyl)methanone;((3R,4R)-4-((6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)((1R,2S)-2-fluorocyclopropyl)methanone;((37?,47?)-4-((7-ethoxy-6-(17 / -pyrazol-4-yl)thieno[3,2-<7]pyrimidin-2-yl)amino)-3-hy droxypiperi din-1 -yl)((LS',27?)-2-fluorocyclopropyl)methanone;((3R,4R)-4-((7-ethoxy-6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)((1R,2S)-2-fluorocyclopropyl)methanone;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONcyclopropyl((3R,4R)-4-((7-ethoxy-6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)methanone;((3R,4R)-4-((7-ethoxy-6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)(1-(trifluoromethyl)cyclopropyl)methanone;(1-(difluoromethyl)cyclopropyl)((3R,4R)-4-((7-ethoxy-6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)methanone;1-((3R,4R)-4-((7-ethoxy-6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)butan-1-one;2-cyclopropyl-l-((3R,4R)-4-((7-Ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)ethan-l-one;l-((3R,4R)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)-3-hy droxypiperidin- 1 -y 1 )- 3,3 -difluoropropan- 1 -one;((3R,4R)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hy droxypiperidin- l-yl)(3-fluorobicyclo[l.l.l]pentan-l-yl)methanone;((3R,4R)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)-3-hy droxypiperidin- 1 -yl)(tetrahy dro-2H-pyran-4-yl)methanone;(l,l-dioxidothietan-3-yl)((3R,4R)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)-3-hy droxypiperidin- 1 -yl)methanone;(l-(difluoromethyl)cyclopropyl)((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thi eno[3,2-d]pyrimi din-2 -yl)amino)piperidin-l-yl)methanone;((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;((lS,2R)-2-fluorocyclopropyl)((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;cyclopropyl((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)piperidin-l-yl)methanone;1-((3R,4R)-3-hydroxy-4-((7-methoxy-6-(1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-1-yl)butan-1-one;((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-y l)amino)piperidin- 1 -yl)( 1 -methylcy clopropyl)methanone;(3,3-difluorocyclobutyl)((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION(3-fluorobicyclo[l.l.l]pentan-l-yl)((3R.4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thi eno[3,2-d]pyrimidin-2-yl)amino)piperi din-1 -yl)methanone;ethyl (37?,47?)-4-((7-ethoxy-6-(177-pyrazol-4-yl)thieno[3,2-<7|pyrimidin-2-yl)amino)-3-hydroxypiperidine-1 -carboxylate;((3R,4R)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3.2-d]pyrimidin-2-yl)amino)-3-hy droxypiperidin- 1 -yl)(morpholino)methanone;methyl (3R,4S)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-methylpiperidine-l -carboxylate;cyclopropyl((3R,4S)-4-((7-ethoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2-yl)amino)-3-methylpiperidin-l-yl)methanone;(3,3-difluoroazetidin-l-yl)((3R,4R)-3-hydroxy-4-((7-methoxy-6-(lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;6-(2-(((3<S',4?)-3-hydroxytetrahydro-277-pyran-4-yl)amino)thieno[2,3-<7]pyrimidin-6-yl)-2-methoxypyridin-3-ol;2-ethoxy-6-(2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)thieno[2,3-d]pyrimidin-6-yl)pyridin-3-ol;6-(2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)thieno[2,3-d]pyrimi din-6-y l)-2-methylpyri din-3 -ol;6-(2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)thieno[2,3-d]pyrimi din-6-yl)-2-methoxy-5-methylpyridin-3-ol;6-(2-(((3S,4R)-3-hydroxytetrahydro-2H-pyran-4-yl)amino)thieno[2,3-d]pyrimi din-6-yl)-2-(methylamino)pyridin-3-ol;cyclopropyl((37?,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2.3-<7]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;cyclopropyl((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;methyl (3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidine-l -carboxylate;ethyl (3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidine-l -carboxylate;l-((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2.3-d] py rimidin-2-yl)amino)piperidin- 1 -y l)-2-methylpropan- 1 -one;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONl-((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2.3-d]pyrimidin-2-yl)amino)piperidin-l-yl)ethan-l-one;l-((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)butan-l-one;((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2.3-d]pyrimidin- 2-yl)amino)piperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;((lS,2R)-2-fluorocyclopropyl)((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;((lR,2S)-2-fluorocyclopropyl)((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyri din-2 -yl)thieno[2.3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;(l-(difluoromethyl)cyclopropyl)((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;(3-fluorobicyclo[l.l.l]pentan-l-yl)((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2.3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;3-((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyri din-2 -yl)thieno[2.3-d]pyrimi din-2 -yl)amino)piperidine-l -carbonyl)bi cyclofl.

1. l]pentane-l -carbonitrile;(2-oxabicyclo[2.1.1]hexan-4-yl)((3R,4R)-3-hydroxy-4-((6-(5-hydroxy-6-methoxypyridin-2-yl)thieno[2,3-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;ethyl (3,4R)-4-((6-(3-([l,3'-biazetidin]-r-yl)-117-pyrazol-4-yl)thieno[3,2-< / ]pyrimi din-2 -yl)amino)-3-hydroxypiperidine-l -carboxylate;ethyl (3R,4R)-4-((6-(3-(3-(dimethylamino)azetidin-l-yl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperidine-l-carboxylate;ethyl (3R,4R)-3-hydroxy-4-((6-(3-(4-methylpiperazin-l-yl)-lH-pyrazol-4-yl)thi eno[3,2-d]pyrimi din-2 -yl)amino)piperidine-l -carboxylate;ethyl (3R,4R)-3-hydroxy-4-((6-(3-(3-(pyrrolidin-l-yl)azetidin-l-yl)-lH-pyrazol-4-yl)thi eno[3,2-d]pyrimi din-2 -yl)amino)piperidine-l -carboxylate;ethyl (3R,4R)-4-((6-(3-((R)-3-(dimethylamino)pyrrolidin-l-yl)-lH-pyrazol-4-yl)thi eno[3,2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperi dine- 1 -carboxylate;ethyl (3R,4R)-4-((6-(3-((S)-3-(dimethylamino)pyrrolidin-l-yl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperidine-l-carboxylate;ethyl (3R,4R)-4-((6-(3-((dimethylamino)methyl)-lH-pyrazol-4-yl)thieno[3.2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperidine-l-carboxylate;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONethyl (3R,4R)-4-((6-(3-((ethylamino)methyl)-lH-pyrazol-4-yl)thieno[3.2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidine-l -carboxylate;((3R,4R)-4-((6-(3-((dimethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;((3R,4R)-4-((6-(3-((ethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyri mi din-2-yl)amino)-3-hydroxypiperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;2,2-difluoroethyl (3R,4R)-4-((6-(3-((dimethylamino)methyl)-lH-pyrazol-4-yl)thi eno[3,2-d]pyrimi din-2 -yl)amino)-3-hydroxypiperidine-l -carboxylate;(3R,4R)-4-((6-(3-((dimethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;(3R,4R)-4-((6-(3-((ethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-l-(methylsulfonyl)piperidin-3-ol;cyclopropyl((3R,4R)-4-((6-(3-((ethylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-l-yl)methanone;(3R,4R)-4-((6-(3-(azetidin-l-ylmethyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)- 1 -(methyl sulfonyl)piperidin-3-ol;methyl (3R,4R)-3-hydroxy-4-((6-(3-((methylamino)methyl)-lH-pyrazol-4-yl)thieno[3, 2-d]pyrimi din-2 -yl)amino)piperi dine- 1 -carboxylate;methyl (3R,4R)-4-((6-(3-((ethylamino)methyl)-lH-pyrazol-4-yl)thieno[3.2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidine-l -carboxylate;((3R,4R)-4-((6-(3-((cyclobutylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d] py rimidin-2-yl)amino)-3-hy droxy piperidin- 1 -yl)( 1 -(trifluoromethyl)cyclopropyl)methanone;((3R,4R)-3-hydroxy-4-((6-(3-((isopropylamino)methyl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;((3R,4R)-4-((6-(3-((ethylamino)methyl)-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)-3-hydroxypiperidin-1-yl)(1-fluorocyclobutyl)methanone;ethyl (3R,4R)-3-hydroxy-4-((6-(3-(1-methylpyrrolidin-3-yl)-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidine-1-carboxylate;((3R,4R)-3-hydroxy-4-((6-(3-(l-methylazetidin-3-yl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)(l-(trifluoromethyl)cyclopropyl)methanone;Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION4,4,4-trifluoro-1-((3R,4R)-3-hydroxy-4-((6-(3-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-1-yl)butan-1-one;ethyl (3R,4R)-3-hydroxy-4-((6-(3-(l-methylazetidin-3-yl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidine-l -carboxylate; and(l-fluorocyclobutyl)((3R,4R)-3-hydroxy-4-((6-(3-(l-methylpyrrolidin-3-yl)-lH-pyrazol-4-yl)thieno[3,2-d]pyrimidin-2-yl)amino)piperidin-l-yl)methanone;or a pharmaceutically acceptable salt thereof.

104. A pharmaceutical composition comprising the compound of any one of claims 1-103, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

105. A method of inhibiting CDK4, comprising contacting the CDK4 with the compound of any one of claims 1-103, or a pharmaceutically acceptable salt thereof.

106. A method of inhibiting CDK4 in a patient, comprising administering to the patient a compound of any one of claims 1-103, or a pharmaceutically acceptable salt thereof.

107. A method of inhibiting CDK4 and / or CDK2, comprising contacting the CDK4 or CDK2 with the compound of any one of claims 1-103, or a pharmaceutically acceptable salt thereof.

108. A method of inhibiting CDK4 and / or CDK2 in a patient, comprising administering to the patient a compound of any one of claims 1-103, or a pharmaceutically acceptable salt thereof.

109. A method of inhibiting CDK4 and CDK2, comprising contacting the CDK4 and CDK2 with the compound of any one of claims 1-103, or a pharmaceutically acceptable salt thereof.

110. A method of inhibiting CDK4 and CDK2 in a patient, comprising administering to the patient a compound of any one of claims 1-103, or a pharmaceutically acceptable salt thereof.Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION111. A method of treating a disease or disorder associated with CDK4 in a patient, comprising administering to the patient a therapeutically effective amount of the compound of any one of claims 1-103, or pharmaceutically acceptable salt thereof.

112. A method of treating a disease or disorder associated with CDK4 and / or CDK2 in a patient, comprising administering to the patient a therapeutically effective amount of the compound of any one of claims 1-103, or pharmaceutically acceptable salt thereof.

113. A method of treating a disease or disorder associated with CDK4 and CDK2 in a patient, comprising administering to the patient a therapeutically effective amount of the compound of any one of claims 1-103, or pharmaceutically acceptable salt thereof.

114. The method of any one of claims 111-113, wherein the disease or disorder is associated with an amplification of the cyclin El (CCNE1) gene and / or overexpression of CCNE1.

115. The method of any one of claims 113-114, wherein the disease or disorder is cancer.

116. The method of claim 115, wherein the cancer is ovarian cancer, breast cancer, or endometrial cancer.

117. The method of claim 115, wherein the cancer is selected from breast cancer, ovarian cancer, a gynecological cancer, a gastrointestinal cancer, prostate cancer, melanoma, colorectal cancer, endometrial cancer, esophageal cancer, gastric cancer, liposarcoma, Ewing sarcoma, or melanoma.

118. The method of any one of claims 115-117, wherein the cancer is platinum resistant.

119. The method of any one of claims 115-117, wherein the cancer is platinum sensitive.

120. The method of any one of claims 115-117, wherein the cancer is breast cancer which is hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-).Attorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATION121. The method of any one of claims 115-117, wherein the cancer is ovarian cancer.

122. The method of any one of claims 113-121, wherein the administering further comprises administering one or more additional pharmaceutical agents.

123. The method of claim 122, wherein the one or more additional pharmaceutical agents is an aromatase inhibitor, luteinizing hormone-releasing hormone (LHRH) agonist, an antiandrogen, therapy targeting the PI3K / AKT / mT0R (PAM) pathway, a selective estrogen receptor degrader (SERD), a CDK2 inhibitor, a CDK4 / 6 inhibitor, a CDK4 inhibitor, or VEGF-A inhibitor, or a combination thereof.

124. The method of claim 122, wherein the one or more additional pharmaceutical agents is a CDK2 inhibitor which is selected from 8-ethoxy-N-((3R,4S)-3-methyl-l-(methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)-[l,2,4]triazolo[l,5-a]pyridin-2-amine; N-((3R,4S)-l-(cyclopropylsulfonyl)-3-methylpiperidin-4-yl)-8-ethoxy-7-(lH-pyrazol-4-yl)- [1.2.4]triazolo[l,5-a]pyridin-2-amine; 8-isopropoxy-N-((3R,4S)-3-methyl-l-(methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)-[l,2,4]triazolo[l,5-c]pyrimidin-2-amine; 8-(ethoxy-d5)-N-((3R,4S)-3-methyl-l-(methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)- [1.2.4]triazolo[1.5-a]pyridin-2-amine; or 8-isopropoxy-N-((3R,4S)-3-methyl-l- (methylsulfonyl)piperidin-4-yl)-7-(lH-pyrazol-4-yl)-[l,2,4]triazolo[l,5-a]pyridin-2-amine; or a pharmaceutically acceptable salt thereof.

125. The method of claim 122, wherein the one or more pharmaceutical agents is:a VEGF-A inhibitor, which is bevacizumab; ora PAM therapy, which is alpelisib, capivasertib, or everolimus, or a pharmaceutically acceptable salt thereof; ora SERD, which is is fluvestrant, camizestrant, amcenestrant, elacestrant, giredestrant. imlunestrant, rintodestrant, AZD9496, borestrant, taragarestrant, or ZN-c5, or a pharmaceutically acceptable salt thereof; oraCDK4 / 6 inhibitor, which is albociclib, ribociclib, albociclib, abemaciclib, or dalpiciclib, or a pharmaceutically acceptable salt thereof; orAttorney Docket No. 20443-0887WO1 / INCY0571-WO1 PCT APPLICATIONa CDK4 inhibitor, which is atirmociclib. or a pharmaceutically acceptable salt thereof; ora CDK2 inhibitor, which is ebvaciclib, or a pharmaceutically acceptable salt thereof; oran aromatase inhibitor, which is anastrozole. exemestane, letrozole, vorozole. formestane, or fadrozole, or a pharmaceutically acceptable salt thereof; ora LHRH agonist, which is leuprolide, goserelin, triptorelin, histrelin, or buserelin, or a pharmaceutically acceptable salt thereof; oran anti-androgen, which is spironolactone, finasteride, dutasteride, bicalutamide, flutamide, enzalutamide. apalutamide. cyproterone, abiraterone, chlormadinone, clascoterone, megestrol, nilutamide, or darolutamide, or a pharmaceutically acceptable salt thereof.

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