Benzamide ARYL ether analogs comprising an amine linker as inhibitors of the menin-MLL interaction

Abstract

The present disclosure is directed to aryl ether analogs comprising an amine linker, of Formula (I), a stereoisomer, or a pharmaceutically acceptable salt thereof, as inhibitors of the interaction of menin with MLL and MLL fusion proteins, pharmaceutical compositions containing the same, and their use in the treatment of cancer and other diseases mediated by the menin-MLL interaction.

Description

[0001] Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0002] BENZAMIDE ARYL ETHER ANALOGS COMPRISING AN AMINE LINKER AS INHIBITORS OF THE MENIN-MLL INTERACTION

[0003] RELATED APPLICATIONS

[0004] This application claims priority to, and the benefit of, U. S. Provisional Application No. 63 / 763,968, filed February 27, 2025, and U. S. Provisional Application No. 63 / 950,234, filed December 29, 2025, the entire contents of each of which are incorporated herein by reference.

[0005] BACKGROUND

[0006] The mixed-lineage leukemia (MLL), also known as KMT2A, gene encodes a protein that is a histone methyltransferase that is mutated in clinically and biologically distinctive subsets of acute leukemia. Rearranged mixed lineage leukemia (MLL-r) involves recurrent translocations of the 1 lq23 chromosome locus which lead to an aggressive form of acute leukemia with limited therapeutic options. These translocations target the MLL gene creating an oncogenic fusion protein comprising the amino-terminus of MLL fused in frame with more than 60 different fusion protein partners. Menin, a ubiquitously expressed, nuclear protein encoded by the multiple endocrine neoplasia type 1 (MENL) tumor suppressor gene, has a high affinity binding interaction with MLL fusion proteins and is an essential co-factor of oncogenic MLL-r fusion proteins. Disruption of this interaction leads to selective growth inhibition and apoptosis of MLL-r leukemia cells both in vitro and in vivo.

[0007] The interaction between menin and MLL or MLL fusion proteins is an attractive target for therapeutic intervention, and there is a need for novel agents that inhibit the menin-MLL interaction for the treatment of various diseases and conditions, including leukemia, other cancers, and diabetes.

[0008] SUMMARY

[0009] In one aspect, the present disclosure is directed to a compound of Formula I,Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0010]

[0011] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0012] = denotes a single bond or a double bond, as valency permits;

[0013] A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(=O)-, -C(RA1)(RA2)-C(=O)-, and -N=C(NH2)-, wherein no more than one of A, B, D, and E is -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(RA1)(RA2)-C(=O)-, -C(=O)-, or -N=C(NH2)-;

[0014] V is N or CH;

[0015] Y is N or CH;

[0016] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0017] G is absent, O, CH2, or NH, wherein

[0018] when G is absent, X is connected with a nitrogen of Ring A;

[0019] when G is O, CH2, or NH, G is connected with the nitrogen of Ring A;

[0020] W is N or CRW, wherein Rwis H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[0021] X is N or CRX, wherein Rxis absent, H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[0022] Z is Cy2, halo, Ci-6 alkyl, C1-6 haloalkyl, Ci -6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NR1R2, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3, and P(O)Rc3Rd3wherein said Ci-6alkyl, Ci-6haloalkyl, Ci-6cyanoalkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0023] substituents independently selected from Cy2, halo, CN, NO2, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;

[0024] each RA1is independently selected from absent, H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, amino, C1-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH;

[0025] each RA2is independently selected from H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, amino, C1-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH;

[0026] each RA3is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C(O)RZ, and C(O)ORZ, wherein said C1-6 alkyl is optionally substituted with phenyl, C1-6 alkoxy, C1-6 haloalkoxy, CN, NO2, or OH;

[0027] Rzis H, C1-6 alkyl, or phenyl;

[0028] each Cy2is independently selected from Ce-14 aryl, C3-18 cycloalkyl, and 4-18 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from RCy2;

[0029] each RCy2is independently selected from halo, C1-6 alkyl, C 1-6 haloalkyl, C1-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5, wherein said Ci-6alkyl, C1-6 haloalkyl, C1-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5;

[0030] R1is

[0031] (a) H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0032] haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0033] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0034] each Rlsis independently oxo or =NR4a;

[0035] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0036] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0037] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0038] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0039] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0040] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0041] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0042] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0043] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0044] R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0045] each Ra3, Rb3, Rc3, Rd3, Ra5, Rb5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-10 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-10 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0046] each Re3and Re5is independently selected from H, C1-6 alkyl, and CN;

[0047] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0048] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or moreAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0049] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0050] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0051] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0052] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0053] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0054] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0055] In one aspect, the present disclosure is directed to a compound of Formula II,

[0056]

[0057] Formula II,

[0058] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0059] = denotes a single bond or a double bond, as valency permits;

[0060] A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(=O)-Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0061] -C(RA1)(RA2)-C(=O)-, and -N=C(NH2)-, wherein no more than one of A, B, D, and E is -C(RA1)(RA2)-O- -C(RA1)(RA2)-NRA3-, -C(RA1)(RA2)-C(=O)-, -C(=O)-, or -N=C(NH2)-;

[0062] V is N or CH;

[0063] Y is N or CH;

[0064] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0065] G is absent or CH2, wherein:

[0066] when G is absent, X is connected with a nitrogen of Ring A;

[0067] when G is CH2, G is connected with the nitrogen of Ring A;

[0068] W is N or CRW, wherein Rwis H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[0069] X is N or CRX, wherein Rxis absent, H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[0070] each RA1is independently selected from absent, H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, amino, Ci-6 alkylamino, C2-s dialkylamino, CN, NO2, and OH; each RA2is independently selected from H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, amino, Ci-6 alkylamino, C2-s dialkylamino, CN, NO2, and OH; each RA3is independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, C(O)RZ, and C(O)ORZ, wherein said Ci-6 alkyl is optionally substituted with phenyl, Ci-6 alkoxy, Ci-6 haloalkoxy, CN, NO2, or OH;

[0071] Rzis H, Ci-6 alkyl, or phenyl;

[0072] R1is

[0073] (a) H, Ci-6 alkyl, Ci -6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0074] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0075] each Rlsis independently oxo or =NR4a;

[0076] (c) -Ci-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0077] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0078] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0079] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0080] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0081] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0082] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0083] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0084] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0085] R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy,Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0086] C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0087] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0088] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0089] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0090] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0091] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0092] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; andAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0093] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0094] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0095] In one aspect, the present disclosure is directed to a compound of Formula Il-a,

[0096]

[0097] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0098] V is N or CH;

[0099] Y is N or CH;

[0100] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0101] G is absent or CH2, wherein:

[0102] when G is absent, X is connected with a nitrogen of Ring A;

[0103] when G is CH2, G is connected with the nitrogen of Ring A;

[0104] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0105] R1is

[0106] (a) H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0107] cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0108] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0109] each Rlsis independently oxo or =NR4a;

[0110] (c) -Ci-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0111] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0112] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0113] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0114] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0115] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0116] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0117] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3-to 12-membered heterocycloalkyl;

[0118] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3-to 12-membered heterocycloalkyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0119] R2is H, Ci-6 alkyl, C1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, Ci-ehaloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0120] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0121] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0122] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0123] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0124] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl,Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0125] or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);

[0126] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0127] each RNIS independently H, C1-6 alkyl, or C1-6 haloalkyl;

[0128] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0129] In one aspect, the present disclosure is directed to a compound of Formula II-b,

[0130] R1

[0131] I

[0132] zN

[0133] R2

[0134]

[0135] Formula II -b,

[0136] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0137] V is N or CH;

[0138] Y is N or CH;

[0139] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0140] G is absent or CH2, wherein:

[0141] when G is absent, X is connected with a nitrogen of Ring A;

[0142] when G is CH2, G is connected with the nitrogen of Ring A;

[0143] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0144] R1is

[0145] (a) H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0146] haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0147] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0148] each Rlsis independently oxo or =NR4a;

[0149] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0150] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0151] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0152] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0153] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0154] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0155] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0156] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3-to 12-membered heterocycloalkyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0157] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0158] R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0159] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0160] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0161] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0162] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0163] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);

[0164] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0165] each RNIS independently H, C1-6 alkyl, or C1-6 haloalkyl;

[0166] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0167] In one aspect, the present disclosure is directed to a compound of Formula II-c,

[0168]

[0169] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0170] V is N or CH;

[0171] Y is N or CH;

[0172] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0173] G is absent or CH2, wherein:

[0174] when G is absent, X is connected with a nitrogen of Ring A;

[0175] when G is CH2, G is connected with the nitrogen of Ring A;

[0176] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0177] R1isAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0178] (a) H, Ci-6 alkyl, C1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0179] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0180] each Rlsis independently oxo or =NR4a;

[0181] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0182] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0183] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0184] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0185] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0186] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0187] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0188] haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0189] each R3b’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0190] each R3C’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0191] R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0192] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0193] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0194] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’),Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0195] N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0196] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0197] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);

[0198] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0199] each RNIS independently H, C1-6 alkyl, or C1-6 haloalkyl;

[0200] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0201] In one aspect, the present disclosure is directed to a compound of Formula II-d,

[0202]

[0203] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0204] V is N or CH;

[0205] Y is N or CH;

[0206] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0207] G is absent or CH2, wherein:

[0208] when G is absent, X is connected with a nitrogen of Ring A;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0209] when G is CH2, G is connected with the nitrogen of Ring A;

[0210] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0211] R1is

[0212] (a) H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(4-10 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(4-10 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0213] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0214] each Rlsis independently oxo or =NR4a;

[0215] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0216] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0217] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0218] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0219] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0220] each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[0221] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0222] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0223] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0224] R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0225] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0226] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0227] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0228] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0229] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0230] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0231] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0232] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0233] In one aspect, the present disclosure is directed to a compound of Formula Il-e,

[0234]

[0235] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0236] V is N or CH;

[0237] Y is N or CH;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0238] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0239] G is absent or CH2, wherein:

[0240] when G is absent, X is connected with a nitrogen of Ring A;

[0241] when G is CH2, G is connected with the nitrogen of Ring A;

[0242] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0243] R1is

[0244] (a) H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(4-10 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(4-10 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0245] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0246] each Rlsis independently oxo or =NR4a;

[0247] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0248] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0249] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0250] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; orAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0251] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0252] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0253] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0254] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0255] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0256] R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0257] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0258] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0259] alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0260] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0261] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0262] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0263] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0264] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0265] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0266] In one aspect, the present application relates to a pharmaceutical composition comprising a compound of the application, or a pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier.

[0267] In one aspect, the present application relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of the application, or a pharmaceutically acceptable salt, and a pharmaceutically acceptable carrier.

[0268] In one aspect, the present application relates to a pharmaceutical composition comprising a compound of the application, and a pharmaceutically acceptable carrier.

[0269] In one aspect, the present application relates to a pharmaceutical composition comprising a therapeutically effective amount of a compound of the application, and a pharmaceutically acceptable carrier.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0270] The present disclosure further provides a use of a compound of Formula I, II, Il-a, ILb, ILc, ILd, or Il-e, or a stereoisomer, or a pharmaceutically acceptable salt thereof in a method of treating cancer in a patient in need thereof.

[0271] The present disclosure further provides a compound of Formula I, II, Il-a, ILb, II-c, II-d, or Il-e, or a stereoisomer, or a pharmaceutically acceptable salt thereof for use in a method of treating cancer in a patient in need thereof.

[0272] The present disclosure further provides a compound of Formula I, II, Il-a, ILb, II-c, II-d, or Il-e, or a stereoisomer, or a pharmaceutically acceptable salt thereof for use in the manufacture of a medicament for the treatment of cancer in a patient in need thereof.

[0273] The present disclosure further provides a method of inhibiting the interaction between menin and MLL comprising contacting the menin and MLL with an effective amount of a compound of Formula I, II, Il-a, ILb, II-c, ILd, or Il-e, or a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0274] The present disclosure further provides a method of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of a compound of Formula I, II, Il-a, ILb, II-c, ILd, or Il-e, a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0275] The present disclosure further provides a method of inhibiting the interaction between menin and MLL comprising contacting the menin and MLL with a compound of Formula I, II, ILa, ILb, II-c, ILd, or ILe, a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0276] The present disclosure further provides a method of treating cancer in a patient comprising administering to the patient an effective amount of a compound of Formula I, II, ILa, ILb, II-c, ILd, or ILe, a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0277] The present disclosure further provides a method of inhibiting the interaction between menin and MLL comprising contacting the menin and MLL with a compound of Formula I, II, ILa, ILb, ILc, ILd, or ILe, or a stereoisomer, or a pharmaceutically acceptable salt thereof.

[0278] The present disclosure further provides a method of inhibiting the interaction between menin and MLL comprising contacting the menin and MLL with a pharmaceutical composition comprising a compound of Formula I, II, ILa, ILb, ILc, ILd, or ILe, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

[0279] The present disclosure further provides a method of treating cancer in a patient comprising administering to the patient a compound of Formula I, II, ILa, ILb, ILc, ILd, or II-e, a stereoisomer, or a pharmaceutically acceptable salt thereof.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0280] The present disclosure further provides a method of treating cancer in a patient comprising administering to the patient a pharmaceutical composition comprising a compound of Formula I, II, Il-a, Il-b, II-c, Il-d, or Il-e, a stereoisomer, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

[0281] The present disclosure further provides a pharmaceutical composition comprising a compound of Formula I, II, Il-a, Il-b, II-c, Il-d, or Il-e, a stereoisomer, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

[0282] The present disclosure further provides a pharmaceutical composition comprising a salt or crystalline form of a compound of Formula I, II, Il-a, II -b, II-c, Il-d, or Il-e, and at least one pharmaceutically acceptable carrier.

[0283] The present disclosure further provides a compound of Formula I, II, Il-a, Il-b, II-c, II-d, or Il-e, wherein the compound is useful for the treatment of cancer and wherein the compound minimizes hERG binding.

[0284] In some embodiments, present disclosure further provides a method of preparing a compound herein according to a scheme of the present disclosure or synthetic description in the Examples.

[0285] In some embodiments, present disclosure further provides an intermediate useful in the preparation of any one of the compounds herein.

[0286] The details of the disclosure are set forth in the accompanying description below. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, illustrative methods and materials are now described. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be limiting. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0287] DETAILED DESCRIPTION

[0288] In some embodiments, the present disclosure is directed to a compound of Formula I,Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0289]

[0290] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0291] = denotes a single bond or a double bond, as valency permits;

[0292] A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(=O)-, -C(RA1)(RA2)-C(=O)-, and -N=C(NH2)-, wherein no more than one of A, B, D, and E is -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(RA1)(RA2)-C(=O)-, -C(=O)-, or -N=C(NH2)-;

[0293] V is N or CH;

[0294] Y is N or CH;

[0295] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0296] G is absent, O, CH2, or NH, wherein

[0297] when G is absent, X is connected with a nitrogen of Ring A;

[0298] when G is O, CH2, or NH, G is connected with the nitrogen of Ring A;

[0299] W is N or CRW, wherein Rwis H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[0300] X is N or CRX, wherein Rxis absent, H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[0301] Z is Cy2, halo, Ci-6 alkyl, C1-6 haloalkyl, Ci -6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NR1R2, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3,Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0302] S(O)2Rb3, S(O)2NRc3Rd3, and P(O)Rc3Rd3wherein said Ci-6alkyl, Ci-6haloalkyl, Ci-6cyanoalkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Cy2, halo, CN, NO2, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;

[0303] each RA1is independently selected from absent, H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, amino, Ci-6 alkylamino, C2-s dialkylamino, CN, NO2, and OH;

[0304] each RA2is independently selected from H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, amino, Ci-6 alkylamino, C2-s dialkylamino, CN, NO2, and OH;

[0305] each RA3is independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, C(O)RZ, and C(O)ORZ, wherein said Ci-6 alkyl is optionally substituted with phenyl, Ci-6 alkoxy, Ci-6 haloalkoxy, CN, NO2, or OH;

[0306] Rzis H, Ci-6 alkyl, or phenyl;

[0307] each Cy2is independently selected from Ce-14 aryl, C3-18 cycloalkyl, and 4-18 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from RCy2;

[0308] each RCy2is independently selected from halo, Ci-6 alkyl, C 1-6 haloalkyl, Ci-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5, wherein said Ci-6alkyl, Ci-6 haloalkyl, Ci-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5;

[0309] R1is

[0310] (a) H, Ci-6 alkyl, C 1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0311] Ce- io aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0312] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0313] each Rlsis independently oxo or =NR4a;

[0314] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0315] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0316] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0317] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0318] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0319] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0320] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0321] each R3b’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0322] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0323] R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0324] each Ra3, Rb3, Rc3, Rd3, Ra5, Rb5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-10 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-10 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0325] each Re3and Re5is independently selected from H, C1-6 alkyl, and CN;

[0326] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0327] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-memberedAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0328] heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0329] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0330] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0331] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0332] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0333] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0334] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0335] In some embodiments, when = is a double bond, X is C.

[0336] In some embodiments, the present disclosure is directed to a compound of Formula I, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0337] = denotes a single bond;

[0338] A, B, D, and E are each independently selected from -C(RA1)(RA2)-;

[0339] V is N or CH;

[0340] Y is N or CH;

[0341] Ring A is 4-18 membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, and is optionally substituted with one or more R3;

[0342] G is CH2;

[0343] W is N or CRW, wherein Rwis H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0344] X is N or CRX, wherein Rxis absent, H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[0345] Z is Cy2, halo, C1-6 alkyl, C 1 -6 haloalky 1, C 1-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NR1R2, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3, and P(O)Rc3Rd3wherein said Ci-6alkyl, Ci-6haloalkyl, Ci-6cyanoalkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Cy2, halo, CN, NO2, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;

[0346] each RA1is independently selected from H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, amino, Ci-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH; each RA2is independently selected from H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, amino, Ci-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH;

[0347] Rzis H, Ci-6 alkyl, or phenyl;

[0348] each Cy2is independently selected from Ce-14 aryl, C3-18 cycloalkyl, and 4-18 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from RCy2;

[0349] each RCy2is independently selected from halo, Ci-6 alkyl, C 1-6 haloalkyl, Ci-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5, wherein said Ci-6alkyl, Ci-6 haloalkyl, Ci-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0350] R1is

[0351] C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0352] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0353] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0354] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0355] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0356] R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0357] each Ra3, Rb3, Rc3, Rd3, Ra5, Rb5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-10 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-10 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0358] each Re3and Re5is independently selected from H, C1-6 alkyl, and CN;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0359] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0360] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0361] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0362] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0363] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0364] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0365] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0366] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0367] In some embodiments, the present disclosure is directed to a compound of Formula I, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0368] = denotes a single bond;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0369] A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, and -C(RA1)(RA2)-O-, wherein no more than one of A, B, D, and E is -C(RA1)(RA2)-O-;

[0370] V is N or CH;

[0371] Y is N or CH;

[0372] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0373] G is absent or CH2, wherein

[0374] when G is absent, X is connected with a nitrogen of Ring A;

[0375] when G is CH2, G is connected with the nitrogen of Ring A;

[0376] W is N or CRW, wherein Rwis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0377] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0378] Z is Cy2or C(O)NR1R2;

[0379] each RA1is independently selected from absent, H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, CN, and OH;

[0380] each RA2is independently selected from H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, or C1-6 haloalkoxy, CN, and OH;

[0381] each Cy2is independently selected from Ce-14 aryl, C3-18 cycloalkyl, and 4-18 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from RCy2;

[0382] each RCy2is independently selected from halo, C1-6 alkyl, C 1-6 haloalkyl, C1-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, NO2, and ORa5;

[0383] R1is

[0384] (a) H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0385] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0386] each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0387] (c) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0388] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0389] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0390] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0391] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0392] R2is C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, or C2-6 alkynyl, Ce-ioaryl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or

[0393] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0394] each Ra5is independently selected from H, C1-6 alkyl, or C1-6 haloalkyl;

[0395] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0396] each R3is independently H, oxo, N(R4a)(R4b), Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[0397] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, Ci-6alkoxy, wherein the Ci-6alkyl, or C1-6 alkoxy, is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, or N(R4a’)(R4b’),;

[0398] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0399] each R4bis independently H or Ci-6 alkyl,;

[0400] each R4a’ and R4b’ is independently H or Ci-6 alkyl; and

[0401] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0402] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0403] In some embodiments, the present disclosure is directed to a compound of Formula I, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0404] = denotes a single bond;

[0405] A, B, D, and E are each independently selected from -C(RA1)(RA2)-;

[0406] V is N or CH;

[0407] Y is N or CH;

[0408] Ring A is 4-18 membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, and is optionally substituted with one or more R3;

[0409] G is CH2;

[0410] W is N or CRW, wherein Rwis H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[0411] X is N or CRX, wherein Rxis H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[0412] Z is Cy2or C(O)NR1R2;

[0413] each RA1is independently selected from absent, H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, CN, and OH;

[0414] each RA2is independently selected from H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, or Ci-6 haloalkoxy, CN, and OH;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0415] each Cy2is independently selected from Ce-14 aryl, C3-18 cycloalkyl, and 4-18 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from RCy2;

[0416] each RCy2is independently selected from halo, C1-6 alkyl, C 1-6 haloalkyl, C1-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, NO2, and ORa5;

[0417] R1is

[0418] C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0419] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0420] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0421] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0422] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0423] R2is C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, or C2-6 alkynyl, Ce-ioaryl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0424] each Ra5is independently selected from H, C1-6 alkyl, or C1-6 haloalkyl;

[0425] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0426] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0427] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, or Ci-6alkoxy, wherein the Ci-6alkyl or Ci-6 alkoxy is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, or N(R4a’)(R4b’);

[0428] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0429] each R4bis independently H or Ci-6 alkyl;

[0430] each R4a’ and R4b’ is independently H or Ci-6 alkyl; and

[0431] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0432] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0433] In some embodiments, the present disclosure is directed to a compound of Formula I, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0434] = denotes a single bond;

[0435] A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, and -C(RA1)(RA2)-O-, wherein no more than one of A, B, D, and E is -C(RA1)(RA2)-O-;

[0436] V is N or CH;

[0437] Y is N or CH;

[0438] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0439] G is absent or CH2, wherein

[0440] when G is absent, X is connected with a nitrogen of Ring A;

[0441] when G is CH2, G is connected with the nitrogen of Ring A;

[0442] W is N;

[0443] X is CRX, wherein Rxis H;

[0444] Z is C(O)NR1R2;

[0445] each RA1is independently selected from H;

[0446] each RA2is independently selected from H;

[0447] R1isAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0448] (a) Ci-6 alkyl, C1-6 haloalkyl, or 3-12 membered heterocycloalkyl, wherein said Ci-6 alkyl, Ci-ehaloalkyl, or 3-12 membered heterocycloalkyl, are each optionally substituted with 1 substituent independently selected from Rg;

[0449] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0450] each Rlbsis Ci-6alkyl; or

[0451] (c) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0452] each Rlcsis independently C1-6 alkyl;

[0453] R2is C1-6 alkyl; or

[0454] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0455] each Rgis independently selected from C1-6 alkyl;

[0456] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, is optionally substituted with one or more R3a;

[0457] each R3ais independently N(R4a)(R4b);

[0458] each R4ais independently H or C1-6 alkyl; and

[0459] each R4bis independently H.

[0460] In some embodiments, the present disclosure is directed to a compound of Formula I, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0461] = denotes a single bond;

[0462] A, B, D, and E are each independently selected from -C(RA1)(RA2)-;

[0463] V is N or CH;

[0464] Y is N or CH;

[0465] Ring A is 4-18 membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, and is optionally substituted with one or more R3;

[0466] G is CH2;

[0467] W is N;

[0468] X is CRX, wherein Rxis H;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0469] Z is C(O)NR1R2;

[0470] each RA1is independently selected from H;

[0471] each RA2is independently selected from H;

[0472] R1is

[0473] C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0474] each Rlcsis independently C1-6 alkyl;

[0475] R2is C1-6 alkyl;

[0476] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl is optionally substituted with one or more R3a;

[0477] each R3ais independently N(R4a)(R4b);

[0478] each R4ais independently H or C1-6 alkyl; and

[0479] each R4bis independently H.

[0480] In some embodiments, the present disclosure is directed to a compound of Formula II,

[0481]

[0482] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0483] = denotes a single bond or a double bond, as valency permits;

[0484] A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(=O)-, -C(RA1)(RA2)-C(=O)-, and -N=C(NH2)-, wherein no more than one of A, B, D, and E is -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(RA1)(RA2)-C(=O)-, -C(=O)-, or -N=C(NH2)-;

[0485] V is N or CH;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0486] Y is N or CH;

[0487] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0488] G is absent or CH2, wherein:

[0489] when G is absent, X is connected with a nitrogen of Ring A;

[0490] when G is CH2, G is connected with the nitrogen of Ring A;

[0491] W is N or CRW, wherein Rwis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0492] X is N or CRX, wherein Rxis absent, H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0493] each RA1is independently selected from absent, H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, amino, C1-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH; each RA2is independently selected from H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, amino, C1-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH; each RA3is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C(O)RZ, and C(O)ORZ, wherein said C1-6 alkyl is optionally substituted with phenyl, C1-6 alkoxy, C1-6 haloalkoxy, CN, NO2, or OH;

[0494] Rzis H, C1-6 alkyl, or phenyl;

[0495] R1is

[0496] (a) H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0497] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0498] each Rlsis independently oxo or =NR4a;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0499] (c) -Ci-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0500] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0501] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0502] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0503] (e) C3-12cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0504] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0505] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0506] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0507] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0508] R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; orAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0509] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;

[0510] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0511] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0512] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0513] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0514] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0515] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0516] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0517] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0518] In some embodiments, the present disclosure is directed to a compound of Formula II, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0519] = denotes a single bond;

[0520] A, B, D, and E are each independently selected from -C(RA1)(RA2)-;

[0521] V is N or CH;

[0522] Y is N or CH;

[0523] Ring A is 4-18 membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, and is optionally substituted with one or more R3;

[0524] G is CH2 and G is connected with the nitrogen of Ring A;

[0525] W is N or CRW, wherein Rwis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0526] X is N or CRX, wherein Rxis absent, H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0527] each RA1is independently selected from H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, amino, C1-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH; each RA2is independently selected from H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, amino, C1-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH;

[0528] R1is

[0529] C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0530] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0531] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0532] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0533] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0534] R2is H, Ci-6 alkyl, C1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, Ci-ehaloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0535] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0536] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0537] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0538] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0539] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0540] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0541] each RNIS independently H, C1-6 alkyl, or C1-6 haloalkyl;

[0542] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0543] In some embodiments, the present disclosure is directed to a compound of Formula II, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0544] = denotes a single bond;

[0545] A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, and -C(RA1)(RA2)-O-, wherein no more than one of A, B, D, and E is -C(RA1)(RA2)-O-;

[0546] V is N or CH;

[0547] Y is N or CH;

[0548] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0549] G is absent or CH2, wherein

[0550] when G is absent, X is connected with a nitrogen of Ring A;

[0551] when G is CH2, G is connected with the nitrogen of Ring A;

[0552] W is N or CRW, wherein Rwis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0553] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0554] each RA1is independently selected from absent, H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, CN, and OH;

[0555] each RA2is independently selected from H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, or C1-6 haloalkoxy, CN, and OH;

[0556] R1is

[0557] (a) H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0558] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0559] each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0560] (c) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0561] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0562] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0563] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0564] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0565] R2is C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, or C2-6 alkynyl, Ce-ioaryl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or

[0566] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0567] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0568] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0569] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, Ci-6alkoxy, wherein the Ci-6alkyl, or Ci-6 alkoxy, is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, or N(R4a’)(R4b’),;

[0570] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0571] each R4bis independently H or Ci-6 alkyl;

[0572] each R4a’ and R4b’ is independently H or Ci-6 alkyl; and

[0573] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0574] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0575] In some embodiments, the present disclosure is directed to a compound of Formula II, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0576] = denotes a single bond;

[0577] A, B, D, and E are each independently selected from -C(RA1)(RA2)-;

[0578] V is N or CH;

[0579] Y is N or CH;

[0580] Ring A is 4-18 membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, and is optionally substituted with one or more R3;

[0581] G is CH2and G is connected with the nitrogen of Ring A;

[0582] W is N or CRW, wherein Rwis H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[0583] X is N or CRX, wherein Rxis H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[0584] each RA1is independently selected from absent, H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, CN, and OH;

[0585] each RA2is independently selected from H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, or Ci-6 haloalkoxy, CN, and OH;

[0586] R1is

[0587] C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0588] each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[0589] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0590] each R3b’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0591] each R3C’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0592] R2is C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, or C2-6 alkynyl, Ce-ioaryl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0593] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0594] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[0595] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, Ci-6alkoxy, wherein the Ci-6alkyl, or C1-6 alkoxy, is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, or N(R4a’)(R4b’);

[0596] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0597] each R4bis independently H or Ci-6 alkyl;

[0598] each R4a’ and R4b’ is independently H or Ci-6 alkyl; and

[0599] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0600] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0601] In some embodiments, the present disclosure is directed to a compound of Formula II, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0602] = denotes a single bond;

[0603] A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, and -C(RA1)(RA2)-O-, wherein no more than one of A, B, D, and E is -C(RA1)(RA2)-O-;

[0604] V is N or CH;

[0605] Y is N or CH;

[0606] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0607] G is absent or CH2, wherein

[0608] when G is absent, X is connected with a nitrogen of Ring A;

[0609] when G is CH2, G is connected with the nitrogen of Ring A;

[0610] W is N;

[0611] X is CRX, wherein Rxis H;

[0612] each RA1is independently selected from H;

[0613] each RA2is independently selected from H;

[0614] R1is

[0615] (a) C1-6 alkyl, C 1 -6 haloalky 1, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, Ci-ehaloalkyl, or 3-12 membered heterocycloalkyl, are each optionally substituted with 1 substituent independently selected from Rg;

[0616] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0617] each Rlbsis C1-6 alkyl; or

[0618] (c) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0619] each Rlcsis independently C1-6 alkyl;

[0620] R2is C1-6 alkyl; or

[0621] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0622] each Rgis independently selected from Ci-6 alkyl;

[0623] each R3is independently H, oxo, N(R4a)(R4b), Ci-6 alkyl, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6 alkyl, is optionally substituted with one or more R3a;

[0624] each R3ais independently N(R4a)(R4b);

[0625] each R4ais independently H or Ci-6 alkyl; and

[0626] each R4bis independently H.

[0627] In some embodiments, the present disclosure is directed to a compound of Formula II, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0628] = denotes a single bond;

[0629] A, B, D, and E are each independently selected from -C(RA1)(RA2)-;

[0630] V is N or CH;

[0631] Y is N or CH;

[0632] Ring A is 4-18 membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, and is optionally substituted with one or more R3;

[0633] G is CH2 and G is connected with the nitrogen of Ring A;

[0634] W is N;

[0635] X is CRX, wherein Rxis H;

[0636] each RA1is independently selected from H;

[0637] each RA2is independently selected from H;

[0638] R1is

[0639] C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0640] each Rlcsis independently C1-6 alkyl;

[0641] R2is C1-6 alkyl;

[0642] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, is optionally substituted with one or more R3a;

[0643] each R3ais independently N(R4a)(R4b);

[0644] each R4ais independently H or C1-6 alkyl; and

[0645] each R4bis independently H.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0646] In some embodiments, the present disclosure is directed to a compound of Formula II-

[0647] X

[0648]

[0649] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0650] V is N or CH;

[0651] Y is N or CH;

[0652] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0653] G is absent or CH2, wherein:

[0654] when G is absent, X is connected with a nitrogen of Ring A;

[0655] when G is CH2, G is connected with the nitrogen of Ring A;

[0656] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0657] R1is

[0658] (a) H, C1-6 alkyl, C 1 -6 haloalky 1, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 memberedAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0659] heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0660] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0661] each Rlsis independently oxo or =NR4a;

[0662] (c) -Ci-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0663] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0664] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0665] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0666] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0667] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0668] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0669] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0670] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0671] R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0672] alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, Ci-ehaloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0673] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0674] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0675] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0676] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0677] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0678] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0679] each RNIS independently H, C1-6 alkyl, or C1-6 haloalkyl;

[0680] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0681] In some embodiments, the present disclosure is directed to a compound of Formula II-a, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0682] V is N or CH;

[0683] Y is N or CH;

[0684] Ring A is 4-18 membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, and is optionally substituted with one or more R3;

[0685] G is CH2 and G is connected with the nitrogen of Ring A;

[0686] X is N or CRX, wherein Rxis absent, H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0687] R1is

[0688] C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0689] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0690] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0691] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0692] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0693] R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0694] membered heterocycloalkyl)-Ci-6 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0695] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0696] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0697] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0698] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0699] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0700] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0701] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0702] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0703] In some embodiments, the present disclosure is directed to a compound of Formula II-a, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0704] V is N or CH;

[0705] Y is N or CH;

[0706] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0707] G is absent or CH2, wherein

[0708] when G is absent, X is connected with a nitrogen of Ring A;

[0709] when G is CH2, G is connected with the nitrogen of Ring A;

[0710] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0711] R1is

[0712] (a) H, C1-6 alkyl, C 1 -6 haloalky 1, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0713] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0714] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0715] (c) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0716] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0717] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0718] each R3b’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0719] each R3C’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0720] R2is C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, or C2-6 alkynyl, Ce-ioaryl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or

[0721] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0722] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0723] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[0724] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, Ci-6alkoxy, wherein the Ci-6alkyl, or C1-6 alkoxy, is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, or N(R4a’)(R4b’);

[0725] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0726] each R4bis independently H or Ci-6 alkyl;

[0727] each R4a’ and R4b’ is independently H or Ci-6 alkyl; and

[0728] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0729] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0730] In some embodiments, the present disclosure is directed to a compound of Formula II-a, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0731] V is N or CH;

[0732] Y is N or CH;

[0733] Ring A is 4-18 membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0734] G is CH2 and G is connected with the nitrogen of Ring A;

[0735] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0736] R1is

[0737] C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0738] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0739] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0740] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0741] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0742] R2is C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, or C2-6 alkynyl, Ce-ioaryl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0743] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0744] each R3is independently H, oxo, N(R4a)(R4b), Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[0745] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, Ci-6alkoxy, wherein the Ci-6alkyl or C1-6 alkoxy is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, or N(R4a’)(R4b’);

[0746] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0747] each R4bis independently H or Ci-6 alkyl;

[0748] each R4a’ and R4b’ is independently H or Ci-6 alkyl; and

[0749] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0750] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0751] In some embodiments, the present disclosure is directed to a compound of Formula II-a, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0752] V is N or CH;

[0753] Y is N or CH;

[0754] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0755] G is absent or CH2, wherein

[0756] when G is absent, X is connected with a nitrogen of Ring A;

[0757] when G is CH2, G is connected with the nitrogen of Ring A;

[0758] X is CRX, wherein Rxis H;

[0759] R1is

[0760] (a) Ci-6 alkyl, C 1-6 haloalkyl, or 3-12 membered heterocycloalkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, or 3-12 membered heterocycloalkyl, are each optionally substituted with 1 substituent independently selected from Rg;

[0761] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0762] each Rlbsis Ci-6alkyl; orAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0763] (C) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0764] each Rlcsis independently C1-6 alkyl;

[0765] R2is C1-6 alkyl; or

[0766] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0767] each Rgis independently selected from C1-6 alkyl;

[0768] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, is optionally substituted with one or more R3a;

[0769] each R3ais independently N(R4a)(R4b);

[0770] each R4ais independently H or C1-6 alkyl; and

[0771] each R4bis independently H.

[0772] In some embodiments, the present disclosure is directed to a compound of Formula II-a, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0773] V is N or CH;

[0774] Y is N or CH;

[0775] Ring A is 4-18 membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, and is optionally substituted with one or more R3;

[0776] G is CH2 and G is connected with the nitrogen of Ring A;

[0777] X is CRX, wherein Rxis H;

[0778] R1is

[0779] C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0780] each Rlcsis independently C1-6 alkyl;

[0781] R2is C1-6 alkyl;

[0782] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, is optionally substituted with one or more R3a;

[0783] each R3ais independently N(R4a)(R4b);Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0784] each R4ais independently H or Ci-6 alkyl; and

[0785] each R4bis independently H.

[0786] In some embodiments, the present disclosure is directed to a compound of Formula II-

[0787]

[0788] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0789] V is N or CH;

[0790] Y is N or CH;

[0791] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0792] G is absent or CH2, wherein:

[0793] when G is absent, X is connected with a nitrogen of Ring A;

[0794] when G is CH2, G is connected with the nitrogen of Ring A;

[0795] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0796] R1is

[0797] (a) H, Ci-6 alkyl, C1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0798] cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0799] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0800] each Rlsis independently oxo or =NR4a;

[0801] (c) -Ci-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0802] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0803] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0804] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0805] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0806] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0807] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0808] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3-to 12-membered heterocycloalkyl;

[0809] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3-to 12-membered heterocycloalkyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0810] R2is H, Ci-6 alkyl, C1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, Ci-ehaloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0811] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0812] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0813] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0814] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0815] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl,Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0816] or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);

[0817] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0818] each RNIS independently H, C1-6 alkyl, or C1-6 haloalkyl;

[0819] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0820] In some embodiments, the present disclosure is directed to a compound of Formula II-b, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0821] V is N or CH;

[0822] Y is N or CH;

[0823] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0824] G is absent or CH2, wherein

[0825] when G is absent, X is connected with a nitrogen of Ring A;

[0826] when G is CH2, G is connected with the nitrogen of Ring A;

[0827] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0828] R1is

[0829] (a) H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0830] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0831] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0832] (c) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more otherAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0833] heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0834] each Rlcsis independently halo, oxo, Ci-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0835] each R3a’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0836] each R3b’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0837] each R3C’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0838] R2is C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, or C2-6 alkynyl, Ce-ioaryl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or

[0839] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0840] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0841] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[0842] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, Ci-6alkoxy, wherein the Ci-6alkyl or C1-6 alkoxy is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, and N(R4a’)(R4b’);

[0843] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0844] each R4bis independently H or Ci-6 alkyl;

[0845] each R4a’ and R4b’ is independently H or Ci-6 alkyl; andAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0846] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0847] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0848] In some embodiments, the present disclosure is directed to a compound of Formula II-b, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0849] V is N or CH;

[0850] Y is N or CH;

[0851] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0852] G is absent or CH2, wherein

[0853] when G is absent, X is connected with a nitrogen of Ring A;

[0854] when G is CH2, G is connected with the nitrogen of Ring A;

[0855] X is CRX, wherein Rxis H;

[0856] R1is

[0857] (a) C1-6 alkyl, C 1-6 haloalkyl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, or 3-12 membered heterocycloalkyl, are each optionally substituted with 1 substituent independently selected from Rg;

[0858] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0859] each Rlbsis C1-6 alkyl; or

[0860] (c) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0861] each Rlcsis independently C1-6 alkyl;

[0862] R2is C1-6 alkyl; or

[0863] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl;

[0864] each Rgis independently selected from C1-6 alkyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0865] each R3is independently H, oxo, N(R4a)(R4b), Ci-6 alkyl, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6 alkyl, is optionally substituted with one or more R3a;

[0866] each R3ais independently N(R4a)(R4b);

[0867] each R4ais independently H or Ci-6 alkyl; and

[0868] each R4bis independently H.

[0869] In some embodiments, the present disclosure is directed to a compound of Formula II-

[0870] G

[0871] X-0

[0872] . N

[0873] 2

[0874]

[0875] Formula II-c,

[0876] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0877] V is N or CH;

[0878] Y is N or CH;

[0879] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0880] G is absent or CH2, wherein:

[0881] when G is absent, X is connected with a nitrogen of Ring A;

[0882] when G is CH2, G is connected with the nitrogen of Ring A;

[0883] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0884] R1is

[0885] (a) H, C1-6 alkyl, C 1 -6 haloalky 1, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0886] alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0887] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0888] each Rlsis independently oxo or =NR4a;

[0889] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0890] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0891] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0892] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0893] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0894] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0895] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[0896] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3-to 12-membered heterocycloalkyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0897] each R3C’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0898] R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0899] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0900] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0901] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[0902] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0903] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);

[0904] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0905] each RNIS independently H, C1-6 alkyl, or C1-6 haloalkyl;

[0906] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0907] In some embodiments, the present disclosure is directed to a compound of Formula II-c, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0908] V is N or CH;

[0909] Y is N or CH;

[0910] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0911] G is absent or CH2, wherein

[0912] when G is absent, X is connected with a nitrogen of Ring A;

[0913] when G is CH2, G is connected with the nitrogen of Ring A;

[0914] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0915] R1is

[0916] (a) H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0917] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0918] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; orAttorney Docket No.: SYND-068 / 001WO 43707-02997

[0919] (C) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0920] each Rlcsis independently halo, oxo, Ci-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0921] each R3a’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[0922] each R3b’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0923] each R3C’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0924] R2is C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, or C2-6 alkynyl, Ce-ioaryl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or

[0925] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0926] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0927] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[0928] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, Ci-6alkoxy, wherein the Ci-6alkyl or C1-6 alkoxy is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, and N(R4a’)(R4b’);

[0929] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0930] each R4bis independently H or Ci-6 alkyl;

[0931] each R4a’ and R4b’ is independently H or Ci-6 alkyl; and

[0932] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[0933] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0934] In some embodiments, the present disclosure is directed to a compound of Formula II-c, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0935] V is N or CH;

[0936] Y is N or CH;

[0937] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0938] G is absent or CH2, wherein

[0939] when G is absent, X is connected with a nitrogen of Ring A;

[0940] when G is CH2, G is connected with the nitrogen of Ring A;

[0941] X is CRX, wherein Rxis H;

[0942] R1is

[0943] (a) C1-6 alkyl, C 1-6 haloalkyl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, or 3-12 membered heterocycloalkyl, are each optionally substituted with 1 substituent independently selected from Rg;

[0944] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0945] each Rlbsis C1-6 alkyl; or

[0946] (c) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0947] each Rlcsis independently C1-6 alkyl;

[0948] R2is C1-6 alkyl; or

[0949] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0950] each Rgis independently selected from Ci-6 alkyl;

[0951] each R3is independently H, oxo, N(R4a)(R4b), Ci-6 alkyl, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6 alkyl, is optionally substituted with one or more R3a;

[0952] each R3ais independently N(R4a)(R4b);

[0953] each R4ais independently H or Ci-6 alkyl; and

[0954] each R4bis independently H.

[0955] In some embodiments, the present disclosure is directed to a compound of Formula II-d,

[0956]

[0957] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0958] V is N or CH;

[0959] Y is N or CH;

[0960] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0961] G is absent or CH2, wherein:

[0962] when G is absent, X is connected with a nitrogen of Ring A;

[0963] when G is CH2, G is connected with the nitrogen of Ring A;

[0964] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0965] R1is

[0966] (a) H, C1-6 alkyl, C 1 -6 haloalky 1, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0967] Ce- io aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0968] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[0969] each Rlsis independently oxo or =NR4a;

[0970] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[0971] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[0972] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[0973] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[0974] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[0975] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[0976] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0977] each R3b’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0978] each R3C’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[0979] R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[0980] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[0981] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[0982] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0983] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[0984] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);

[0985] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[0986] each RNIS independently H, C1-6 alkyl, or C1-6 haloalkyl;

[0987] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[0988] In some embodiments, the present disclosure is directed to a compound of Formula II-d, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[0989] V is N or CH;

[0990] Y is N or CH;

[0991] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[0992] G is absent or CH2, wherein

[0993] when G is absent, X is connected with a nitrogen of Ring A;

[0994] when G is CH2, G is connected with the nitrogen of Ring A;

[0995] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[0996] R1is

[0997] (a) H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[0998] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[0999] each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[1000] (c) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1001] each Rlcsis independently halo, oxo, Ci-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1002] each R3a’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[1003] each R3b’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1004] each R3C’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1005] R2is C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, or C2-6 alkynyl, Ce-ioaryl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or

[1006] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[1007] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[1008] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1009] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, Ci-6alkoxy, wherein the Ci-6alkyl orAttorney Docket No.: SYND-068 / 001WO 43707-02997

[1010] Ci-6 alkoxy is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, and N(R4a’)(R4b’);

[1011] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1012] each R4bis independently H or Ci-6 alkyl;

[1013] each R4a’ and R4b’ is independently H or Ci-6 alkyl; and

[1014] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[1015] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[1016] In some embodiments, the present disclosure is directed to a compound of Formula II-d, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[1017] V is N or CH;

[1018] Y is N or CH;

[1019] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[1020] G is absent or CH2, wherein

[1021] when G is absent, X is connected with a nitrogen of Ring A;

[1022] when G is CH2, G is connected with the nitrogen of Ring A;

[1023] X is CRX, wherein Rxis H;

[1024] R1is

[1025] (a) C1-6 alkyl, C 1-6 haloalkyl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, or 3-12 membered heterocycloalkyl, are each optionally substituted with 1 substituent independently selected from Rg;

[1026] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[1027] each Rlbsis C1-6 alkyl; or

[1028] (c) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1029] each Rlcsis independently C1-6 alkyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1030] R2is Ci-6 alkyl; or

[1031] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl;

[1032] each Rgis independently selected from Ci-6 alkyl;

[1033] each R3is independently H, oxo, N(R4a)(R4b), Ci-6 alkyl, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6 alkyl, is optionally substituted with one or more R3a;

[1034] each R3ais independently N(R4a)(R4b);

[1035] each R4ais independently H or Ci-6 alkyl; and

[1036] each R4bis independently H.

[1037] In some embodiments, the present disclosure is directed to a compound of Formula II-

[1038]

[1039] a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[1040] V is N or CH;

[1041] Y is N or CH;

[1042] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[1043] G is absent or CH2, wherein:

[1044] when G is absent, X is connected with a nitrogen of Ring A;

[1045] when G is CH2, G is connected with the nitrogen of Ring A;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1046] X is N or CRX, wherein Rxis H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;

[1047] R1is

[1048] (a) H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(4-10 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(4-10 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1049] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[1050] each Rlsis independently oxo or =NR4a;

[1051] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[1052] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[1053] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[1054] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[1055] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1056] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1057] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;

[1058] each R3b’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1059] each R3C’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1060] R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[1061] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[1062] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[1063] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1064] membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1065] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1066] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);

[1067] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1068] each RNIS independently H, C1-6 alkyl, or C1-6 haloalkyl;

[1069] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[1070] In some embodiments, the present disclosure is directed to a compound of Formula II-e, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[1071] V is N or CH;

[1072] Y is N or CH;

[1073] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[1074] G is absent or CH2, wherein

[1075] when G is absent, X is connected with a nitrogen of Ring A;

[1076] when G is CH2, G is connected with the nitrogen of Ring A;

[1077] X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;

[1078] R1is

[1079] (a) H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1080] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[1081] each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[1082] (c) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1083] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1084] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1085] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1086] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1087] R2is C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, or C2-6 alkynyl, Ce-ioaryl, or 3-12 membered heterocycloalkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, or 3-12 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or

[1088] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[1089] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[1090] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1091] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, Ci-6alkoxy, wherein the Ci-6alkyl or Ci-6 alkoxy is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, and N(R4a’)(R4b’);

[1092] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1093] each R4bis independently H or Ci-6 alkyl;

[1094] each R4a’ and R4b’ is independently H or Ci-6 alkyl; and

[1095] each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;

[1096] wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

[1097] In some embodiments, the present disclosure is directed to a compound of Formula II-e, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:

[1098] V is N or CH;

[1099] Y is N or CH;

[1100] Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[1101] G is absent or CH2, wherein

[1102] when G is absent, X is connected with a nitrogen of Ring A;

[1103] when G is CH2, G is connected with the nitrogen of Ring A;

[1104] X is CRX, wherein Rxis H;

[1105] R1is

[1106] (a) Ci-6 alkyl, Ci -6 haloalkyl, or 3-12 membered heterocycloalkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, or 3-12 membered heterocycloalkyl, are each optionally substituted with 1 substituent independently selected from Rg;

[1107] (b) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[1108] each Rlbsis Ci-6alkyl; or

[1109] (c) C3-12cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more otherAttorney Docket No.: SYND-068 / 001WO 43707-02997

[1110] heteroatom ring members and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1111] each Rlcsis independently C1-6 alkyl;

[1112] R2is C1-6 alkyl; or

[1113] R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl;

[1114] each Rgis independently selected from C1-6 alkyl;

[1115] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, is optionally substituted with one or more R3a;

[1116] each R3ais independently N(R4a)(R4b);

[1117] each R4ais independently H or C1-6 alkyl; and

[1118] each R4bis independently H.

[1119] Embodiments

[1120] For any of Formulae I, II, Il-a, Il-b, II-c, Il-d, and Il-e where applicable, the following embodiments are considered both alone and in conjunction with another where a stable compound is formed.

[1121] Embodiments covering A, B, D, andE

[1122] In some embodiments, A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(=O)--C(RA1)(RA2)-C(=O)-, and -N=C(NH2)-, wherein no more than one of A, B, D, and E is -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(RA1)(RA2)-C(=O)-, -C(=O)-, or -N=C(NH2)-.

[1123] In some embodiments, A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, and -C(RA1)(RA2)-O-.

[1124] In some embodiments, B is -C(RA1)(RA2)-.

[1125] In some embodiments, B is -C(RA1)(RA2)-C(RA1)(RA2)-.

[1126] In some embodiments, B is -C(RA1)(RA2)-O- In some embodiments, B is -C(RA1)(RA2)-, wherein RA1is absent.

[1127] In some embodiments, B is -C(RA1)(RA2)-C(RA1)(RA2)-, wherein one RA1is absent. In some embodiments, B is -C(RA1)(RA2)-O-, wherein RA1is absent.

[1128] In some embodiments, B is -C(RA2)-.

[1129] In some embodiments, B is -C(RA2)-C(RA1)(RA2)-.

[1130] In some embodiments, B is -C(RA2)-O-Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1131] Embodiments covering RA1

[1132] In some embodiments, each RA1is independently selected from absent, H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-ehaloalkyl, Ci-6 haloalkoxy, amino, Ci-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH.

[1133] In some embodiments, each RA1is independently selected from absent, H, and C1-6 alkyl.

[1134] In some embodiments, RA1is absent.

[1135] In some embodiments, RA1is H.

[1136] In some embodiments, RA1is C1-6 alkyl.

[1137] Embodiments covering R'2

[1138] In some embodiments, each RA2is independently selected from H, halo, C1-6 alkyl, Ci-6 alkoxy, Ci-ehaloalkyl, C1-6 haloalkoxy, amino, C 1-6 alkyl amino, C2-8 dialkylamino, CN, NO2, and OH.

[1139] In some embodiments, each RA2is independently selected from H and C1-6 alkyl. Embodiments covering RA3

[1140] In some embodiments, each RA3is independently selected from H, C1-6 alkyl, C1-6 alkoxy, Ci-ehaloalkyl, C(O)RZ, and C(O)ORZ, wherein said C1-6 alkyl is optionally substituted with phenyl, C1-6 alkoxy, C1-6 haloalkoxy, CN, NO2, or OH; and

[1141] Rzis H, C1-6 alkyl, or phenyl.

[1142] In some embodiments, each RA3is independently selected from H and C1-6 alkyl. Embodiments covering V

[1143] In some embodiments, V is N or CH.

[1144] In some embodiments, V is N.

[1145] In some embodiments, V is CH.

[1146] Embodiments covering Y

[1147] In some embodiments, Y is N or CH.

[1148] In some embodiments, Y is N.

[1149] In some embodiments, Y is CH.

[1150] Embodiments covering G

[1151] In some embodiments, Gis absent, O, CH2, orNH, wherein

[1152] when G is absent, X is connected with a nitrogen of Ring A;

[1153] when G is O, CH2, or NH, G is connected with the nitrogen of Ring A.

[1154] In some embodiments, Gis absent, O, CH2, orNH.

[1155] In some embodiments, G is absent and X is connected with a nitrogen of Ring A.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1156] In some embodiments, G is O and G is connected with the nitrogen of Ring A.

[1157] In some embodiments, G is CH2 and G is connected with the nitrogen of Ring A. In some embodiments, G is NH and G is connected with the nitrogen of Ring A.

[1158] Embodiments covering Ring A

[1159] In some embodiments, Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[1160] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[1161] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1162] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1163] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1164] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1165] In some embodiments, Ring A is 4-18 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl is optionally substituted with one or more R3;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1166] each R3is independently H, oxo, N(R4a)(R4b), Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1167] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1168] each R4ais independently H or C1-6 alkyl; and

[1169] each R4bis independently H or C1-6 alkyl.

[1170] In some embodiments, Ring A is 4-17 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-17 membered heterocycloalkyl is optionally substituted with one or more R3;

[1171] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1172] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1173] each R4ais independently H or C1-6 alkyl; and

[1174] each R4bis independently H or C1-6 alkyl.

[1175] In some embodiments, Ring A is 4-16 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-16 membered heterocycloalkyl is optionally substituted with one or more R3;

[1176] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1177] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1178] each R4ais independently H or C1-6 alkyl; and

[1179] each R4bis independently H or C1-6 alkyl.

[1180] In some embodiments, Ring A is 4-15 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-15 membered heterocycloalkyl is optionally substituted with one or more R3;

[1181] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1182] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1183] each R4ais independently H or C1-6 alkyl; and

[1184] each R4bis independently H or C1-6 alkyl.

[1185] In some embodiments, Ring A is 4-14 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-14 membered heterocycloalkyl is optionally substituted with one or more R3;

[1186] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1187] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1188] each R4ais independently H or C1-6 alkyl; and

[1189] each R4bis independently H or C1-6 alkyl.

[1190] In some embodiments, Ring A is 4-13 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-13 membered heterocycloalkyl is optionally substituted with one or more R3;

[1191] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1192] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1193] each R4ais independently H or C1-6 alkyl; and

[1194] each R4bis independently H or C1-6 alkyl.

[1195] In some embodiments, Ring A is 4-12 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-12 membered heterocycloalkyl is optionally substituted with one or more R3;

[1196] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1197] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1198] each R4ais independently H or C1-6 alkyl; and

[1199] each R4bis independently H or C1-6 alkyl.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1200] In some embodiments, Ring A is 4-11 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-11 membered heterocycloalkyl is optionally substituted with one or more R3;

[1201] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1202] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1203] each R4ais independently H or C1-6 alkyl; and

[1204] each R4bis independently H or C1-6 alkyl.

[1205] In some embodiments, Ring A is 4-10 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-10 membered heterocycloalkyl is optionally substituted with one or more R3;

[1206] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1207] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1208] each R4ais independently H or C1-6 alkyl; and

[1209] each R4bis independently H or C1-6 alkyl.

[1210] In some embodiments, Ring A is 4-9 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-9 membered heterocycloalkyl is optionally substituted with one or more R3;

[1211] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1212] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1213] each R4ais independently H or C1-6 alkyl; and

[1214] each R4bis independently H or C1-6 alkyl.

[1215] In some embodiments, Ring A is 4-8 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-8 membered heterocycloalkyl is optionally substituted with one or more R3;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1216] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1217] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1218] each R4ais independently H or C1-6 alkyl; and

[1219] each R4bis independently H or C1-6 alkyl.

[1220] In some embodiments, Ring A is 4-7 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-7 membered heterocycloalkyl is optionally substituted with one or more R3;

[1221] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1222] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1223] each R4ais independently H or C1-6 alkyl; and

[1224] each R4bis independently H or C1-6 alkyl.

[1225] In some embodiments, Ring A is 4-6 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-6 membered heterocycloalkyl is optionally substituted with one or more R3;

[1226] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1227] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1228] each R4ais independently H or C1-6 alkyl; and

[1229] each R4bis independently H or C1-6 alkyl.

[1230] In some embodiments, Ring A is 4-5 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-5 membered heterocycloalkyl is optionally substituted with one or more R3;

[1231] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1232] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1233] each R4ais independently H or C1-6 alkyl; and

[1234] each R4bis independently H or C1-6 alkyl.

[1235] In some embodiments, Ring A is 4-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-membered heterocycloalkyl is optionally substituted with one or more R3;

[1236] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1237] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1238] each R4ais independently H or C1-6 alkyl; and

[1239] each R4bis independently H or C1-6 alkyl.

[1240] In some embodiments, Ring A is 5-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 5 -membered heterocycloalkyl is optionally substituted with one or more R3;

[1241] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1242] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1243] each R4ais independently H or C1-6 alkyl; and

[1244] each R4bis independently H or C1-6 alkyl.

[1245] In some embodiments, Ring A is 6-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 6-membered heterocycloalkyl is optionally substituted with one or more R3;

[1246] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1247] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1248] each R4ais independently H or C1-6 alkyl; and

[1249] each R4bis independently H or C1-6 alkyl.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1250] In some embodiments, Ring A is 7-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 7-membered heterocycloalkyl is optionally substituted with one or more R3;

[1251] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1252] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1253] each R4ais independently H or C1-6 alkyl; and

[1254] each R4bis independently H or C1-6 alkyl.

[1255] In some embodiments, Ring A is 8-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 8-membered heterocycloalkyl is optionally substituted with one or more R3;

[1256] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1257] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1258] each R4ais independently H or C1-6 alkyl; and

[1259] each R4bis independently H or C1-6 alkyl.

[1260] In some embodiments, Ring A is 9-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 9-membered heterocycloalkyl is optionally substituted with one or more R3;

[1261] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1262] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1263] each R4ais independently H or C1-6 alkyl; and

[1264] each R4bis independently H or C1-6 alkyl.

[1265] In some embodiments, Ring A is 10-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 10-membered heterocycloalkyl is optionally substituted with one or more R3;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1266] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1267] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1268] each R4ais independently H or C1-6 alkyl; and

[1269] each R4bis independently H or C1-6 alkyl.

[1270] In some embodiments, Ring A is 11 -membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 11 -membered heterocycloalkyl is optionally substituted with one or more R3;

[1271] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1272] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1273] each R4ais independently H or C1-6 alkyl; and

[1274] each R4bis independently H or C1-6 alkyl.

[1275] In some embodiments, Ring A is 12-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 12-membered heterocycloalkyl is optionally substituted with one or more R3;

[1276] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1277] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1278] each R4ais independently H or C1-6 alkyl; and

[1279] each R4bis independently H or C1-6 alkyl.

[1280] In some embodiments, Ring A is 13-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 13 -membered heterocycloalkyl is optionally substituted with one or more R3;

[1281] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1282] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1283] each R4ais independently H or C1-6 alkyl; and

[1284] each R4bis independently H or C1-6 alkyl.

[1285] In some embodiments, Ring A is 14-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 14-membered heterocycloalkyl is optionally substituted with one or more R3;

[1286] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1287] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1288] each R4ais independently H or C1-6 alkyl; and

[1289] each R4bis independently H or C1-6 alkyl.

[1290] In some embodiments, Ring A is 15-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 15 -membered heterocycloalkyl is optionally substituted with one or more R3;

[1291] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1292] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1293] each R4ais independently H or C1-6 alkyl; and

[1294] each R4bis independently H or C1-6 alkyl.

[1295] In some embodiments, Ring A is 16-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 16-membered heterocycloalkyl is optionally substituted with one or more R3;

[1296] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1297] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1298] each R4ais independently H or C1-6 alkyl; and

[1299] each R4bis independently H or C1-6 alkyl.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1300] In some embodiments, Ring A is 17-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 17-membered heterocycloalkyl is optionally substituted with one or more R3;

[1301] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1302] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1303] each R4ais independently H or C1-6 alkyl; and

[1304] each R4bis independently H or C1-6 alkyl.

[1305] In some embodiments, Ring A is 18-membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 18 -membered heterocycloalkyl is optionally substituted with one or more R3;

[1306] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1307] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1308] each R4ais independently H or C1-6 alkyl; and

[1309] each R4bis independently H or C1-6 alkyl.

[1310]

[1311] Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1312]

[1313] Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1314]

[1315] In some embodiments, Ring A is 5- to 10-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;

[1316] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1317] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1318] each R4ais independently H or C1-6 alkyl; and

[1319] each R4bis independently H or C1-6 alkyl.

[1320] In some embodiments, Ring A is 5- to 9-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 5- to 9-membered heteroaryl is optionally substituted with one or more R3;

[1321] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1322] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1323] each R4ais independently H or C1-6 alkyl; and

[1324] each R4bis independently H or C1-6 alkyl.

[1325] In some embodiments, Ring A is 5- to 8-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 5- to 8-membered heteroaryl is optionally substituted with one or more R3;

[1326] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1327] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1328] each R4ais independently H or C1-6 alkyl; and

[1329] each R4bis independently H or C1-6 alkyl.

[1330] In some embodiments, Ring A is 5- to 7-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 5- to 7-membered heteroaryl is optionally substituted with one or more R3;

[1331] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1332] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1333] each R4ais independently H or C1-6 alkyl; and

[1334] each R4bis independently H or C1-6 alkyl.

[1335] In some embodiments, Ring A is 5- to 6-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 5- to 6-membered heteroaryl is optionally substituted with one or more R3;

[1336] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1337] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1338] each R4ais independently H or C1-6 alkyl; and

[1339] each R4bis independently H or C1-6 alkyl.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1340] In some embodiments, Ring A is 5-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 5-membered heteroaryl is optionally substituted with one or more R3;

[1341] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1342] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1343] each R4ais independently H or C1-6 alkyl; and

[1344] each R4bis independently H or C1-6 alkyl.

[1345] In some embodiments, Ring A is 6-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 6-membered heteroaryl is optionally substituted with one or more R3;

[1346] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1347] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1348] each R4ais independently H or C1-6 alkyl; and

[1349] each R4bis independently H or C1-6 alkyl.

[1350] In some embodiments, Ring A is 7-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 7-membered heteroaryl is optionally substituted with one or more R3;

[1351] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1352] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1353] each R4ais independently H or C1-6 alkyl; and

[1354] each R4bis independently H or C1-6 alkyl.

[1355] In some embodiments, Ring A is 8-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 8-membered heteroaryl is optionally substituted with one or more R3;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1356] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1357] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1358] each R4ais independently H or C1-6 alkyl; and

[1359] each R4bis independently H or C1-6 alkyl.

[1360] In some embodiments, Ring A is 9-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 9-membered heteroaryl is optionally substituted with one or more R3;

[1361] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1362] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1363] each R4ais independently H or C1-6 alkyl; and

[1364] each R4bis independently H or C1-6 alkyl.

[1365] In some embodiments, Ring A is 10-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 10-membered heteroaryl is optionally substituted with one or more R3;

[1366] each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;

[1367] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);

[1368] each R4ais independently H or C1-6 alkyl; and

[1369] each R4bis independently H or C1-6 alkyl.

[1370] In some embodiments, Ring A is

[1371]

[1372] Embodiments covering W

[1373] In some embodiments, W is N or CRW, wherein Rwis H, halo, CN, OH, C1-6 alkyl, Ci-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1374] In some embodiments, W is CRW, wherein Rwis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino.

[1375] In some embodiments, W is N.

[1376] In some embodiments, W is CH.

[1377] Embodiments covering X

[1378] In some embodiments, X is N or CRX, wherein Rxis absent, H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino.

[1379] In some embodiments, X is N.

[1380] In some embodiments, X is CRX, wherein Rxis absent, H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino.

[1381] In some embodiments, X is CH.

[1382] In some embodiments, X is C.

[1383] In some embodiments, when = is a double bond, X is C.

[1384] Embodiments covering the Spiro Moiety

[1385] In some embodiments, the spiro moiety represented by the below formula:

[1386] e

[1387] X

[1388] AxB

[1389] D; >

[1390] w

[1391] ux Irv

[1392]

[1393] f

[1394] wherein e and f indicate points of attachment to the remainder of the molecule, is selected from:Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1395]

[1396] In some embodiments, the spiro moiety represented by the below formula:Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1397] e

[1398]

[1399] wherein e and f indicate points of attachment to the remainder of the molecule, is selected from:

[1400]

[1401] Embodiments covering Z

[1402] In some embodiments, Z is Cy2, halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NR1R2, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3, and P(O)Rc3Rd3wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 cyanoalkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Cy2, halo, CN, NO2, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;

[1403] each Cy2is independently selected from Ce-14 aryl, C3-18 cycloalkyl, and 4-18 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from RCy2;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1404] each RCy2is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5;

[1405] R1is

[1406] (a) H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(4-10 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(4-10 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1407] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[1408] each Rlsis independently oxo or =NR4a;

[1409] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[1410] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1411] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[1412] each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[1413] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1414] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1415] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1416] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1417] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1418] R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;

[1419] each Ra3, Rb3, Rc3, Rd3, Ra5, Rb5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-10 cycloalkyl, 5-10 memberedAttorney Docket No.: SYND-068 / 001WO 43707-02997

[1420] heteroaryl, 4-10 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-10 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(4-10 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-10 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(4-10 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1421] each Re3and Re5is independently selected from H, C1-6 alkyl, and CN;

[1422] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[1423] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);

[1424] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1425] each RNis independently H, C1-6 alkyl, or C1-6 haloalkyl.

[1426] In some embodiments, Z is C(O)NR1R2, wherein R1and R2are as defined above. In some embodiments, Z is C(O)NR1R2, wherein:

[1427] R1is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1428] R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1429] membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1430] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[1431] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1432] each RNis independently H, C1-6 alkyl, or C1-6 haloalkyl.

[1433] In some embodiments, Z is C(O)NR1R2, wherein:

[1434] R1is 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[1435] each Rlsis independently oxo or =NR4a;

[1436] R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-i2cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1437] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[1438] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1439] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1440] each RNis independently H, C1-6 alkyl, or C1-6 haloalkyl.

[1441] In some embodiments, Z is C(O)NR1R2, wherein:Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1442] R1is -Ci-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[1443] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[1444] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1445] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1446] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1447] R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1448] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[1449] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1450] each RNis independently H, C1-6 alkyl, or C1-6 haloalkyl.

[1451] In some embodiments, Z is C(O)NR1R2, wherein:

[1452] R1is 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1453] each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[1454] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1455] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1456] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1457] R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1458] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[1459] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1460] each RNis independently H, C1-6 alkyl, or C1-6 haloalkyl.

[1461] In some embodiments, Z is C(O)NR1R2, wherein:

[1462] R1is C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1463] each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[1464] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1465] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1466] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1467] R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1468] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[1469] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1470] each RNis independently H, C1-6 alkyl, or C1-6 haloalkyl.

[1471] In some embodiments, Z is C(O)NR1R2, wherein R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy.

[1472] Embodiments covering R1

[1473] In some embodiments, R1is:Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1474] (a) H, Ci-6 alkyl, C1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1475] (b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[1476] each Rlsis independently oxo or =NR4a;

[1477] (c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;

[1478] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[1479] (d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[1480] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or

[1481] (e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1482] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1483] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1484] haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1485] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1486] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;

[1487] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[1488] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1489] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1490] each RNis independently H, C1-6 alkyl, or C1-6 haloalkyl.

[1491] In some embodiments, R1is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce- 10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1492] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[1493] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1494] each RNis independently H, C1-6 alkyl, or C1-6 haloalkyl.

[1495] In some embodiments, R1is C1-6 alkyl.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1496] In some embodiments, R1is C1-5 alkyl.

[1497] In some embodiments, R1is C1-6 alkyl.

[1498] In some embodiments, R1is C1-3 alkyl.

[1499] In some embodiments, R1is C1-2 alkyl.

[1500] In some embodiments, R1is methyl.

[1501] In some embodiments, R1is ethyl.

[1502] In some embodiments, R1is propyl.

[1503] In some embodiments, R1is isopropyl.

[1504] In some embodiments, R1is butyl.

[1505] In some embodiments, R1is tert-butyl.

[1506] In some embodiments, R1is pentyl.

[1507] In some embodiments, R1is hexyl.

[1508] In some embodiments, R1is C 1 -6 haloalky 1.

[1509] In some embodiments, R1is C1-3 haloalkyl.

[1510] In some embodiments, R1is C 1-2 haloalkyl.

[1511] In some embodiments, R1is -CH2-CF3, -CH2-CHF2, or -CH2-CH2F.

[1512] In some embodiments, R1is -CH2-CHF2.

[1513] In some embodiments, R1is C1-6 alkoxy.

[1514] In some embodiments, R1is C2-6 alkenyl.

[1515] In some embodiments, R1is C2-6 alkynyl.

[1516] In some embodiments, R1is Ce-ioaryl.

[1517] In some embodiments, R1is C3-12 cycloalkyl.

[1518] In some embodiments, R1is 5-10 membered heteroaryl.

[1519] In some embodiments, R1is 3-12 membered heterocycloalkyl.

[1520] In some embodiments, R1is -Ce-io aryl-Ci-6 alkyl.

[1521] In some embodiments, R1is -C3-12 cycloalkyl -C1-6 alkyl.

[1522] In some embodiments, R1is -(5-10 membered heteroaryl)-Ci-6 alkyl.

[1523] In some embodiments, R1is -(4-10 membered heterocycloalkyl)-Ci-6 alkyl.

[1524] In some embodiments, R1is 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;

[1525] each Rlsis independently oxo or =NR4a;

[1526] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); andAttorney Docket No.: SYND-068 / 001WO 43707-02997

[1527] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1528] In some embodiments, R1is -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3 -12 cycloalkylene is optionally substituted with one or more Rlas;

[1529] each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[1530] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1531] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1532] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1533] In some embodiments, R1is 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;

[1534] each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;

[1535] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1536] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1537] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1538] In some embodiments, R1is C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1539] each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[1540] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1541] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1542] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1543] In some embodiments, R1is C3-11 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-11 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1544] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1545] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1546] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1547] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1548] In some embodiments, R1is C3-10 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-10 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1549] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1550] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1551] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1552] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1553] In some embodiments, R1is C3-9 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-9 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1554] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1555] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1556] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1557] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1558] In some embodiments, R1is C3-8 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-8 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1559] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1560] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1561] each R3b’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1562] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1563] In some embodiments, R1is C3-7 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-7 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1564] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1565] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1566] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1567] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1568] In some embodiments, R1is C3-6 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-6 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1569] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1570] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1571] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1572] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1573] In some embodiments, R1is C3-5 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-5 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1574] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1575] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1576] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1577] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1578] In some embodiments, R1is C3-4 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-4 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1579] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1580] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1581] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1582] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1583] In some embodiments, R1is cyclopropyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclopropyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1584] each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[1585] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1586] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1587] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1588] In some embodiments, R1is cyclobutyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclobutyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1589] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1590] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1591] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1592] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1593] In some embodiments, R1is cyclopentyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclopentyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1594] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1595] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1596] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1597] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1598] In some embodiments, R1is cyclohexyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclohexyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1599] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1600] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1601] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1602] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1603] In some embodiments, R1is cycloheptyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cycloheptyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1604] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1605] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1606] each R3b’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1607] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1608] In some embodiments, R1is cyclooctyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclooctyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1609] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1610] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1611] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1612] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1613] In some embodiments, R1is cyclononyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclononyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1614] each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;

[1615] each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1616] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1617] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1618] In some embodiments, R1is cyclodecyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the cyclodecyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;

[1619] each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;

[1620] each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;

[1621] each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1622] each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1623] In some embodiments, R

[1624]

[1625] 1is, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the heterocycloalkyl is optionally substituted.

[1626] B

[1627] In some embodiments, R

[1628]

[1629] 1is, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the heterocycloalkyl is optionally substituted.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1630] In some embodiments, R

[1631]

[1632] 1is, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the heterocycloalkyl is optionally substituted.

[1633] B

[1634] In some embodiments, R

[1635]

[1636] 1is "w, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the heterocycloalkyl is optionally substituted, wherein RBnis an optionally substituted Ci-6 alkyl.

[1637] B

[1638] In some embodiments, R

[1639]

[1640] 1isnnnr, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the heterocycloalkyl is optionally substituted, wherein RBnis an optionally substituted Ci-6 alkyl.

[1641] In some embodiments, R

[1642]

[1643] 1isnnnr, wherein Ring B is a 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the heterocycloalkyl is optionally substituted, wherein RBnis an optionally substituted Ci-6 alkyl.

[1644] In some embodiments, RBnis an optionally substituted Ci alkyl.

[1645] In some embodiments, RBnis an optionally substituted C2 alkyl.

[1646] In some embodiments, RBnis an optionally substituted C3 alkyl.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1647] In some embodiments, RBnis a Ci alkyl. In some embodiments, RBnis a C2 alkyl. In some embodiments, RBnis a C3 alkyl.

[1648] In some embodiments, R1is

[1649] In some embodiments,

[1650]

[1651] R1is

[1652] In some embodiments,

[1653]

[1654] R1is

[1655] In some embodiments,

[1656]

[1657] R1is

[1658] N

[1659] In some embodiments,

[1660]

[1661] R1is

[1662] In some embodiments,

[1663]

[1664] R1is

[1665] In some embodiments,

[1666]

[1667] R1is

[1668] In some embodiments,

[1669]

[1670] R1isAttorney Docket No.: SYND-068 / 001WO 43707-02997

[1671] HNS<

[1672] In some embodiments,

[1673]

[1674] R1is.

[1675] Embodiments covering R2

[1676] In some embodiments, R2is H, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce- 10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;

[1677] each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;

[1678] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; and

[1679] each RNis independently H, C1-6 alkyl, or C1-6 haloalkyl.

[1680] In some embodiments, R2is H.

[1681] In some embodiments, R2is C1-6 alkyl.

[1682] In some embodiments, R2is C1-5 alkyl.

[1683] In some embodiments, R2is C1-6 alkyl.

[1684] In some embodiments, R2is C1-3 alkyl.

[1685] In some embodiments, R2is C1-2 alkyl.

[1686] In some embodiments, R2is methyl.

[1687] In some embodiments, R2is ethyl.

[1688] In some embodiments, R2is propyl.

[1689] In some embodiments, R2is isopropyl.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1690] In some embodiments, R2is butyl.

[1691] In some embodiments, R2is tert-butyl.

[1692] In some embodiments, R2is pentyl.

[1693] In some embodiments, R2is hexyl.

[1694] Embodiments covering R1and R2

[1695] In some embodiments, R1and R2optionally form a 3 - to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1696] In some embodiments, R1and R2optionally form a 3 - to 11 -membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1697] In some embodiments, R1and R2optionally form a 3 - to 10-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1698] In some embodiments, R1and R2optionally form a 3 - to 9-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1699] In some embodiments, R1and R2optionally form a 3 - to 8-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1700] In some embodiments, R1and R2optionally form a 3 - to 7-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1701] In some embodiments, R1and R2optionally form a 3 - to 6-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1702] In some embodiments, R1and R2optionally form a 3 - to 5-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1703] In some embodiments, R1and R2optionally form a 3 - to 4-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1704] In some embodiments, R1and R2optionally form a 3 -membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1705] In some embodiments, R1and R2optionally form a 4-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1706] In some embodiments, R1and R2optionally form a 5 -membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1707] In some embodiments, R1and R2optionally form a 6-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1708] In some embodiments, R1and R2form a 6-membered heterocycloalkyl with the nitrogen to which they are connected, the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1709] In some embodiments, R1and R2form I group with the nitrogen to which they are connected.

[1710]

[1711] In some embodiments, R1and R2form = group with the nitrogen to which they are connected.

[1712] In some embodiments, R1and R2optionally form a 7-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1713] In some embodiments, R1and R2optionally form a 8-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1714] In some embodiments, R1and R2optionally form a 9-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1715] In some embodiments, R1and R2optionally form a 10-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1716] In some embodiments, R1and R2optionally form a 11 -membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

[1717] Embodiments covering R3

[1718] In some embodiments, each R3is independently H, oxo, N(R4a)(R4b), Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;

[1719] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;

[1720] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1721] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1722] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1723] In some embodiments, R3is H.

[1724] In some embodiments, R3is oxo.

[1725] In some embodiments, R3is N(R4a)(R4b), wherein:

[1726] R4ais H, CN, or Ci-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’);Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1727] R4bis H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1728] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -i2cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1729] In some embodiments, R3is -NH2.

[1730] In some embodiments, R3is C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted with one or more R3a;

[1731] each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl;

[1732] each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);

[1733] each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’); and

[1734] each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1735] In some embodiments, R3is Ci-6 alkyl substituted with one N(R4a)(R4b), wherein: R4ais H or Ci-6 alkyl; and

[1736] R4bis H or Ci-6 alkyl.

[1737] In some embodiments, R3is -CH2-NH2.

[1738] In some embodiments, R3is Ci-6 alkyl.

[1739] In some embodiments, R3is C1-5 alkyl.

[1740] In some embodiments, R3is Ci-6 alkyl.

[1741] In some embodiments, R3is C1-3 alkyl.

[1742] In some embodiments, R3is C1-2 alkyl.

[1743] In some embodiments, R3is methyl.

[1744] In some embodiments, R3is ethyl.

[1745] In some embodiments, R3is propyl.

[1746] In some embodiments, R3is isopropyl.

[1747] In some embodiments, R3is butyl.Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1748] In some embodiments, R3is tert-butyl.

[1749] In some embodiments, R3is pentyl.

[1750] In some embodiments, R3is hexyl.

[1751] In some embodiments, R3is C2-6 alkenyl.

[1752] In some embodiments, R3is C2-6 alkynyl.

[1753] In some embodiments, R3is C1-6 alkoxy.

[1754] In some embodiments, R3is C3-12 cycloalkyl.

[1755] In some embodiments, R3is Ce-io aryl.

[1756] In some embodiments, R3is 5- to 10-membered heteroaryl.

[1757] In some embodiments, R3is 3- to 12-membered heterocycloalkyl.

[1758] In some embodiments, R3is C(O)(R4a), wherein:

[1759] R4ais H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[1760] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1761] In some embodiments, R3is C(O)(OR4a), wherein:

[1762] R4ais H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[1763] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1764] In some embodiments, R3is C(O)O-C(R4a)2-OC(O)(R4a), wherein:

[1765] each R4ais independently H, CN, or C1-6 alkyl optionally substituted with one or more halo, Ce-io aryl, or N(R4a’)(R4b’); and

[1766] each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.

[1767] Exemplary Combinations

[1768] In some embodiments, V is CH, Y is N, and G is CH2 and G is connected with the nitrogen of Ring A.

[1769] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1770] of Ring A; and Ring A is

[1771]

[1772] Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1773]

[1774] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1775]

[1776] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen NH2

[1777] of Ring A; and Ring A

[1778]

[1779] is or

[1780] In some embodiments, V is CH, Y is N, G is CH2 and G is connected with the nitrogen of Ring A, and R2is isopropyl.

[1781] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1782] of Ring A; and Ring A is

[1783]

[1784] Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1785]

[1786] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1787]

[1788] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen NH2

[1789] N=\

[1790] of Ring A; Ring A

[1791]

[1792] is or; and R2is isopropyl.

[1793] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1794] of Ring A; and R1is ethyl, isopropyl, -

[1795]

[1796] CH2-CHF2,Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1797] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1798] of Ring A; and R1is ethyl, isopropyl, -

[1799]

[1800] CH2-CHF2, or

[1801] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the

[1802]

[1803] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1804]

[1805] Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1806] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the

[1807] and R1is ethyl,

[1808]

[1809] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen NH2

[1810] of Ring A; Ring A is; and R1is ethyl, isopropyl, -CH2-

[1811] C

[1812]

[1813] HF2, or In some embodiments, V is CH, Y is N, G is CH2 and G is connected with the nitrogen

[1814] of Ring A; R1is ethyl, isopropyl, -

[1815]

[1816] CH2-CHF2,; and R2is isopropyl.

[1817] In some embodiments, V is CH, Y is N, G is CH2 and G is connected with the nitrogen

[1818] of Ring A; R1is ethyl, isopropyl, -

[1819]

[1820] CH2-CHF2, or and R2is isopropyl.

[1821] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1822]

[1823] Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1824]

[1825] opyl.

[1826] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1827]

[1828] opyl.

[1829] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1830]

[1831] Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1832] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogenH2N\_NH2

[1833] N=\ of Ring A; Ring A is, or; R1is ethyl, isopropyl, -CH2-CHF2,

[1834]

[1835] and R2is isopropyl.

[1836] In some embodiments, V is CH, Y is N, G is CH2 and G is connected with the nitrogen

[1837] of Ring A, and R1and R2form I v group with the nitrogen to which they are connected.

[1838] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1839]

[1840] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1841]

[1842] Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1843] NH2NH2NH2

[1844] O'

[1845] N N

[1846]

[1847] / wv- « / vw / vw or; and R1and R2form group with the nitrogen to which they are connected.

[1848] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen H2N N H2N NH2

[1849] N=\ O' N

[1850] of Ring A; Ring A

[1851]

[1852] is, or; and R1and R2form

[1853]

[1854] group with the nitrogen to which they are connected.

[1855] In some embodiments, V is CH, Y is N, G is CH2 and G is connected with the nitrogen e e

[1856] of Ring A; and the spiro moiety represented by the below formula:

[1857]

[1858] * is

[1859]

[1860] wherein e and f indicate points of attachment to the remainder of the molecule.

[1861] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1862]

[1863] Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1864] e e

[1865] ; and the spiro moiety represented by the below formula: * is

[1866]

[1867] wherein e and f indicate points of attachment to the remainder of the molecule.

[1868] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1869]

[1870] of attachment to the remainder of the molecule.

[1871] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen NH2

[1872] of Ring A; Ring A is

[1873]

[1874] or; and the spiro moiety representedAttorney Docket No.: SYND-068 / 001WO 43707-02997

[1875] e e

[1876] £

[1877] by the below formula:

[1878]

[1879] 1is, or wherein e and f indicate points of attachment to the remainder of the molecule.

[1880] In some embodiments, V is CH, Y is N, G is CH2 and G is connected with the nitrogen e > / w X

[1881] K zBD_E W

[1882] > A I / V of Ring A, R2is isopropyl; and the spiro moiety represented by the below formula:fis

[1883]

[1884] the remainder of the molecule.

[1885] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1886]

[1887] Attorney Docket No.: SYND-068 / 001WO 43707-02997

[1888] e

[1889]

[1890]

[1891] ; R2is isopropyl; and the spiro moiety represented by the below formula:

[1892]

[1893]

[1894] the remainder of the molecule.

[1895] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1896]

[1897] indicate points of attachment to the remainder of the molecule.

[1898] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen NH2

[1899] of Ring A; Ring A is

[1900]

[1901] or; R2is isopropyl; and the spiro moietyAttorney Docket No.: SYND-068 / 001WO 43707-02997

[1902] e e

[1903] D, E W represented by the below formula:

[1904]

[1905] fwherein e and f indicate points of attachment to the remainder of the molecule.

[1906] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1907] of Ring A; R1is ethyl, isopropyl, -

[1908]

[1909] CH2-CHF2,; and the

[1910] A B

[1911] spiro moiety represented by the below formula:

[1912]

[1913] f, or

[1914]

[1915] N

[1916] wherein e and f indicate points of attachment to the remainder of the molecule.

[1917] In some embodiments, V is CH; Y is N; G is CH2 and G is connected with the nitrogen

[1918] of Ring A; R1is ethyl, isopropyl, -

[1919]

[1920] CH2-CHF2, or; and the spiro moiety represented by

[1921] A 'B

[1922] N

[1923] the below formula:

[1924]

[1925] * is wherein e and f indicate ...

Claims

1. Attorney Docket No.: SYND-068 / 001WO 43707-02997CLAIMSWhat is claimed is:

1. A compound of Formula I,a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:= denotes a single bond or a double bond, as valency permits;A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(=O)-, -C(RA1)(RA2)-C(=O)-, and -N=C(NH2)-, wherein no more than one of A, B, D, and E is -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(RA1)(RA2)-C(=O)-, -C(=O)-, or -N=C(NH2)-;V is N or CH;Y is N or CH;Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;G is absent, O, CH2, or NH, whereinwhen G is absent, X is connected with a nitrogen of Ring A;when G is O, CH2, or NH, G is connected with the nitrogen of Ring A;W is N or CRW, wherein Rwis H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;Attorney Docket No.: SYND-068 / 001WO 43707-02997X is N or CRX, wherein Rxis absent, H, halo, CN, OH, Ci-6 alkyl, Ci-6 alkoxy, amino, Ci-6 alkyl amino, or C2-8 dialkylamino;Z is Cy2, halo, C1-6 alkyl, C 1 -6 haloalky 1, C 1-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NR1R2, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, S(O)2NRc3Rd3, and P(O)Rc3Rd3wherein said Ci-6alkyl, Ci-6haloalkyl, Ci-6cyanoalkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from Cy2, halo, CN, NO2, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;each RA1is independently selected from absent, H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, amino, Ci-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH; each RA2is independently selected from H, halo, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, amino, Ci-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH; each RA3is independently selected from H, Ci-6 alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, C(O)RZ, and C(O)ORZ, wherein said Ci-6 alkyl is optionally substituted with phenyl, Ci-6 alkoxy, Ci-6 haloalkoxy, CN, NO2, or OH;Rzis H, Ci-6 alkyl, or phenyl;each Cy2is independently selected from Ce-14 aryl, C3-18 cycloalkyl, and 4-18 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from RCy2;each RCy2is independently selected from halo, Ci-6 alkyl, C 1-6 haloalkyl, Ci-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, C(=NRe5)NRc5Rd5, NRc5C(=NRe5)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5, wherein said Ci-6alkyl, Ci-6 haloalkyl, Ci-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, C3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from CN, NO2, ORa5, SRa5, C(O)Rb5, C(O)NRc5Rd5, C(O)ORa5, OC(O)Rb5, OC(O)NRc5Rd5, C(=NRe5)NRc5Rd5,Attorney Docket No.: SYND-068 / 001WO 43707-02997NRc5C(=NRe5)NRc5Rd5, NRc5Rd5, NRc5C(O)Rb5, NRc5C(O)ORa5, NRc5C(O)NRc5Rd5, NRc5S(O)Rb5, NRc5S(O)2Rb5, NRc5S(O)2NRc5Rd5, S(O)Rb5, S(O)NRc5Rd5, S(O)2Rb5, and S(O)2NRc5Rd5;R1is(a) H, Ci-6 alkyl, C1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-i2 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- io aryl -Ci -6 alkyl, -C3-i2cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-i2 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-i2 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;(b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;each Rlsis independently oxo or =NR4a;(c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-i2 cycloalkylene is optionally substituted with one or more Rlas;each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;(d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-i2 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or(e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-i2 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;Attorney Docket No.: SYND-068 / 001WO 43707-02997each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;each Ra3, Rb3, Rc3, Rd3, Ra5, Rb5, Rc5, and Rd5is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-10 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-10 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;each Re3and Re5is independently selected from H, C1-6 alkyl, and CN;each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6Attorney Docket No.: SYND-068 / 001WO 43707-02997haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkyl sulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; andeach RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

2. The compound of claim 1, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein when = is a double bond, X is C.Attorney Docket No.: SYND-068 / 001WO 43707-029973. The compound of any one of the preceding claims, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein the spiro moiety represented by the below formula:wherein e and f indicate points of attachment to the remainder of the molecule, is selected from:Attorney Docket No.: SYND-068 / 001WO 43707-029974. A compound of Formula II,Formula II,a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:= denotes a single bond or a double bond, as valency permits;A, B, D, and E are each independently selected from -O-, -C(RA1)(RA2)-, -C(RA1)(RA2)-C(RA1)(RA2)-, -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(=O)-, -C(RA1)(RA2)-C(=O)-, and -N=C(NH2)-, wherein no more than one of A, B, D, and E is -C(RA1)(RA2)-O-, -C(RA1)(RA2)-NRA3-, -C(RA1)(RA2)-C(=O)-, -C(=O)-, or -N=C(NH2)-;V is N or CH;Attorney Docket No.: SYND-068 / 001WO 43707-02997Y is N or CH;Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;G is absent or CH2, wherein:when G is absent, X is connected with a nitrogen of Ring A;when G is CH2, G is connected with the nitrogen of Ring A;W is N or CRW, wherein Rwis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;X is N or CRX, wherein Rxis absent, H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;each RA1is independently selected from absent, H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, amino, C1-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH; each RA2is independently selected from H, halo, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, amino, C1-6 alkylamino, C2-8 dialkylamino, CN, NO2, and OH; each RA3is independently selected from H, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C(O)RZ, and C(O)ORZ, wherein said C1-6 alkyl is optionally substituted with phenyl, C1-6 alkoxy, C1-6 haloalkoxy, CN, NO2, or OH;Rzis H, C1-6 alkyl, or phenyl;R1is(a) H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;(b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;each Rlsis independently oxo or =NR4a;Attorney Docket No.: SYND-068 / 001WO 43707-02997(c) -Ci-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;(d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or(e) C3-12cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; orAttorney Docket No.: SYND-068 / 001WO 43707-02997R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy;each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; andeach RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.Attorney Docket No.: SYND-068 / 001WO 43707-029975. A compound of Formula Il-a,a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:V is N or CH;Y is N or CH;Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;G is absent or CH2, wherein:when G is absent, X is connected with a nitrogen of Ring A;when G is CH2, G is connected with the nitrogen of Ring A;X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;R1is(a) H, C1-6 alkyl, C 1 -6 haloalky 1, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;Attorney Docket No.: SYND-068 / 001WO 43707-02997(b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;each Rlsis independently oxo or =NR4a;(c) -Ci-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;(d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or(e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;R2is H, C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C 1-6 haloalkyl, C1-6 alkoxy,Attorney Docket No.: SYND-068 / 001WO 43707-02997C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; andAttorney Docket No.: SYND-068 / 001WO 43707-02997each RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

6. A compound of Formula II-b,R1. NR2V,N Formula II -b, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:V is N or CH;Y is N or CH;Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;G is absent or CH2, wherein:when G is absent, X is connected with a nitrogen of Ring A;when G is CH2, G is connected with the nitrogen of Ring A;X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;R1is(a) H, Ci-6 alkyl, Ci -6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10Attorney Docket No.: SYND-068 / 001WO 43707-02997membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;(b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;each Rlsis independently oxo or =NR4a;(c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;(d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or(e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3-to 12-membered heterocycloalkyl;each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3-to 12-membered heterocycloalkyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997R2is H, Ci-6 alkyl, C1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(3-12 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, Ci-ehaloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3- 12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(3-12 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl,Attorney Docket No.: SYND-068 / 001WO 43707-02997or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; andeach RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

7. A compound of Formula II-c,GX-0. N2N Formula II-c, a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:V is N or CH;Y is N or CH;Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;G is absent or CH2, wherein:when G is absent, X is connected with a nitrogen of Ring A;when G is CH2, G is connected with the nitrogen of Ring A;X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;R1isAttorney Docket No.: SYND-068 / 001WO 43707-02997(a) H, Ci-6 alkyl, C1-6 haloalkyl, Ci-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;(b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;each Rlsis independently oxo or =NR4a;(c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;(d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or(e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6Attorney Docket No.: SYND-068 / 001WO 43707-02997haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with Ci-6 alkoxy;each R3b’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;each R3C’ is independently H, Ci-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, CI-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’),Attorney Docket No.: SYND-068 / 001WO 43707-02997N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl is optionally substituted with C1-6 alkoxy or C(O)N(R4a’)(R4b’);each R4a’ and R4b’ is independently H, C1-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; andeach RNIS independently H, C1-6 alkyl, or C1-6 haloalkyl;wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

8. A compound of Formula II-d,a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:V is N or CH;Y is N or CH;Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;G is absent or CH2, wherein:Attorney Docket No.: SYND-068 / 001WO 43707-02997when G is absent, X is connected with a nitrogen of Ring A;when G is CH2, G is connected with the nitrogen of Ring A;X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;R1is(a) H, C1-6 alkyl, C 1 -6 haloalky 1, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;(b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;each Rlsis independently oxo or =NR4a;(c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;(d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;each Rlbsis independently halo, oxo, OR3a’, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or(e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;Attorney Docket No.: SYND-068 / 001WO 43707-02997each Rlcsis independently halo, oxo, Ci-6 alkyl, Ci-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the Ci-6 alkyl or Ci-6 haloalkyl is optionally substituted with one or more Ci-6 alkoxy;each R3a’ is independently H, Ci-6 alkyl, Ci-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;each R3is independently H, oxo, N(R4a)(R4b), C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;Attorney Docket No.: SYND-068 / 001WO 43707-02997each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; andeach RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

9. A compound of Formula Il-e,a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein:V is N or CH;Attorney Docket No.: SYND-068 / 001WO 43707-02997Y is N or CH;Ring A is 4-18 membered heterocycloalkyl or 5- to 10-membered heteroaryl, each of which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl or the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;G is absent or CH2, wherein:when G is absent, X is connected with a nitrogen of Ring A;when G is CH2, G is connected with the nitrogen of Ring A;X is N or CRX, wherein Rxis H, halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, amino, C1-6 alkyl amino, or C2-8 dialkylamino;R1is(a) H, C1-6 alkyl, C 1 -6 haloalky 1, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-io aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, - Ce- 10 aryl -Ci -6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, or -(4-10 membered heterocycloalkyl)-Ci-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, Ce-ioaryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -Ce-io aryl-Ci-6 alkyl, -C3-12 cycloalkyl-Ci-6 alkyl, -(5-10 membered heteroaryl)-Ci-6 alkyl, and -(4-10 membered heterocycloalkyl)-Ci-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;(b) 3- to 12-membered heterocycloalkyl comprising a sulfur atom, wherein the sulfur atom of the 3- to 12-membered heterocycloalkyl is optionally substituted with one or two Rls;each Rlsis independently oxo or =NR4a;(c) -C1-6 alkylene-N(R3a’)(R3b’) or -C3-12 cycloalkylene-N(R3a’)(R3b’), wherein the C1-6 alkylene or C3-12 cycloalkylene is optionally substituted with one or more Rlas;each Rlasis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’;(d) 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlbs;Attorney Docket No.: SYND-068 / 001WO 43707-02997each Rlbsis independently halo, oxo, OR3a’, Ci-6 alkyl, Ci-6 haloalkyl, C3-12 cycloalkyl, 3- to 12-membered heterocycloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), or S(=O)2R3a’; or(e) C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12- membered heterocycloalkyl is optionally substituted with one or more Rlcs;each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;each R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl;R2is H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, or -(3-12 membered heterocycloalkyl)-C1-6 alkyl, wherein said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-12 cycloalkyl, 5-10 membered heteroaryl, 3-12 membered heterocycloalkyl, -C6-10 aryl-C1-6 alkyl, -C3-12 cycloalkyl-C1-6 alkyl, -(5-10 membered heteroaryl)-C1-6 alkyl, and -(3-12 membered heterocycloalkyl)-C1-6 alkyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg; or R1and R2optionally form a 3- to 12-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is optionally substituted with one or more C1-6 alkyl, halo, OH, CN, or C1-6 alkoxy;each Rgis independently selected from OH, NO2, CN, halo, oxo, OBn, N(RN)2, C1-6 alkyl, Ce-io aryl, 5- to 10-membered heteroaryl, N(R4a’)(R4b’), C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-6 cycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-Ci-3 alkyl, HO-C1-3 alkyl, amino, C1-6 alkylamino, di(Ci-6 alkyl)amino, thiol, C 1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carboxy, aminocarbonyl, C1-6 alkylcarbonyl, and C1-6 alkoxycarbonyl;Attorney Docket No.: SYND-068 / 001WO 43707-02997each R3is independently H, oxo, N(R4a)(R4b), Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, 3- to 12-membered heterocycloalkyl, C(O)(R4a), C(O)(OR4a), or C(O)O-C(R4a)2-OC(O)(R4a), wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl is optionally substituted with one or more R3a;each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), S(=O)2R4b’, N(R4a)(R4b), Ci-6alkyl, C3-12 cycloalkyl, Ci-6alkoxy, C6-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the Ci-6 alkyl, C3-12 cycloalkyl, Ci-6 alkoxy, Ce-io aryl, 3- to 12-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituent independently selected from halo, O(R4a’), oxo, CN, C(O)OR4a’, OC(O)N(R4a’)(R4b’), N(R4a’)(R4b’), N(R4a’)C(O)(R4b’), N(R4a’)C(O)O(R4b’), Ci-6 alkyl that is optionally substituted with O(R4a), and 3- to 12-membered heterocycloalkyl that is optionally substituted with oxo;each R4ais independently H, CN, or Ci-6 alkyl optionally substituted with one or more halo, C6-io aryl, or N(R4a’)(R4b’);each R4bis independently H, S(=O)2R4b’, C(O)OR4b’, C(O)R4b’, C(O)NR4a’R4b’, C(O)CH2-N(R4a’)(R4b’), Ci-6 alkyl, C3-12 cycloalkyl, Ce-io aryl, 5- to 10-membered heteroaryl, or 3- to 12-membered heterocycloalkyl, wherein the Ci-6 alkyl is optionally substituted with Ci-6 alkoxy or C(O)N(R4a’)(R4b’);each R4a’ and R4b’ is independently H, Ci-6 alkyl, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; andeach RN is independently H, Ci-6 alkyl, or Ci-6 haloalkyl;wherein any cycloalkyl or heterocycloalkyl group is optionally further substituted with 1 or 2 oxo groups.

10. The compound of any one of the preceding claims, wherein V is N.

11. The compound of any one of the preceding claims, wherein V is CH.

12. The compound of any one of the preceding claims, wherein Y is N.

13. The compound of any one of the preceding claims, wherein Y is CH.Attorney Docket No.: SYND-068 / 001WO 43707-0299714. The compound of any one of the preceding claims, wherein G is absent and X is CH which is connected with a nitrogen of Ring A.

15. The compound of any one of the preceding claims, wherein G is CH2 and G is connected with the nitrogen of Ring A.

16. The compound of any one of the preceding claims, wherein W is N.

17. The compound of any one of the preceding claims, wherein R1is C1-6 alkyl or Ci-Ce haloalkyl.

18. The compound of any one of the preceding claims, wherein R1is ethyl, isopropyl, or -CH2-CHF2.

19. The compound of any one of the preceding claims, wherein R1is C3-12 cycloalkyl substituted with one or more 3- to 12-membered heterocycloalkyl which has at least one nitrogen and optionally one or more other heteroatom ring members; and wherein each of the C3-12 cycloalkyl and the 3- to 12-membered heterocycloalkyl is optionally substituted with one or more Rlcs;each Rlcsis independently halo, oxo, C1-6 alkyl, C1-6 haloalkyl, C(=O)(R3a’), N(R3a’)(R3b’), OR3a’, or S(=O)2R3a’, wherein the C1-6 alkyl or C1-6 haloalkyl is optionally substituted with one or more C1-6 alkoxy;each R3a’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C(O)R3c’, C3 -12 cycloalkyl, or 3- to 12-membered heterocycloalkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl are optionally substituted with C1-6 alkoxy;each R3b’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl; andeach R3C’ is independently H, C1-6 alkyl, C1-6 haloalkyl, C3-12 cycloalkyl, or 3- to 12-membered heterocycloalkyl.Attorney Docket No.: SYND-068 / 001WO 43707-0299720. The compound of any one of the preceding claims, wherein R1is21. The compound of any one of the preceding claims, wherein R1and R2form a 6-membered heterocycloalkyl with the nitrogen to which they are connected, wherein the heterocycloalkyl is substituted with one or more Ci-6 alkyl, halo, OH, CN, or Ci-6 alkoxy.

22. The compound of any one of the preceding claims, wherein R2is Ci-6 alkyl.

23. The compound of any one of the preceding claims, wherein R2is isopropyl.O' 24. The compound of any one of the preceding claims, wherein R1and R2formgroup with the nitrogen to which they are connected.

25. The compound of any one of the preceding claims, wherein Ring A is 4-18 membered heterocycloalkyl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 4-18 membered heterocycloalkyl is optionally substituted with one or more R3;each R3is independently H, oxo, N(R4a)(R4b), Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);each R4ais independently H or C1-6 alkyl; andeach R4bis independently H or C1-6 alkyl.Attorney Docket No.: SYND-068 / 001WO 43707-0299727. The compound of any one of the preceding claims, wherein Ring A is 5- to 10-membered heteroaryl having at least one nitrogen and optionally one or more other heteroatom ring members, wherein the 5- to 10-membered heteroaryl is optionally substituted with one or more R3;each R3is independently H, oxo, N(R4a)(R4b), Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkoxy is optionally substituted with one or more R3a;each R3ais independently halo, OR4a, oxo, C(O)O(R4a), CN, C(=O)N(R4a)(R4b), OC(O)N(R4a)(R4b), or N(R4a)(R4b);each R4ais independently H or C1-6 alkyl; andeach R4bis independently H or C1-6 alkyl.

28. The compound of any one of the preceding claims, wherein Ring A isAttorney Docket No.: SYND-068 / 001WO 43707-0299729. The compound of any one of the preceding claims, wherein each R3is independently H, methyl, -CH2-NH2, oxo, or -NH2.

30. A compound as shown in Table 1 or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.

31. A compound as shown in Table 1 or a pharmaceutically acceptable salt thereof.

32. A compound as shown in Table 1.

33. A compound as shown in Table 1 or a pharmaceutically acceptable salt thereof, wherein the salt is hydrochloride.

34. The compound according to any one of the preceding claims, wherein the compound is useful for the treatment of cancer and wherein the compound minimizes hERG binding.

35. A pharmaceutical composition comprising a compound of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

36. A pharmaceutical composition comprising a salt or crystalline form of the compound of any one of claims 1-34, and at least one pharmaceutically acceptable carrier.

37. A method of inhibiting the interaction between menin and MLL comprising contacting the menin and MLL with a compound of any one of claims 1-34 or a pharmaceutical composition of claim 35 or claim 36.

38. A method of treating cancer in a patient comprising administering to the patient a compound of any one of claims 1-34 or a pharmaceutical composition of claim 35 or claim 36.

39. The method of claim 38, wherein the cancer is a hematological cancer.

40. The method of claim 38, wherein the cancer is a leukemia or lymphoma.Attorney Docket No.: SYND-068 / 001WO 43707-0299741. The method of claim 38, wherein the cancer is mixed lineage leukemia (MLL), MLL-related leukemia, MLL-associated leukemia, MLL-positive leukemia, MLL-induced leukemia, rearranged mixed lineage (KMT2A-rearranged) leukemia (MLL-r), leukemia associated with a MLL rearrangement or a rearrangement of the MLL gene, acute leukemia, chronic leukemia, indolent leukemia, lymphoblastic leukemia, lymphocytic leukemia, myeloid leukemia, myelogenous leukemia, childhood leukemia, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), acute granulocytic leukemia, acute nonlymphocytic leukemia, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), therapy related leukemia, myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), myeloproliferative neoplasia (MPN), plasma cell neoplasm, multiple myeloma, myelodysplasia, cutaneous T-cell lymphoma, lymphoid neoplasm, AIDS-related lymphoma, thymoma, thymic carcinoma, mycosis fungoides, Alibert-Bazin syndrome, granuloma fungoides, Sezary Syndrome, hairy cell leukemia, T-cell prolymphocytic leukemia (T-PLL), large granular lymphocytic leukemia, meningeal leukemia, leukemic leptomeningitis, leukemic meningitis, multiple myeloma, Hodgkin's lymphoma, non Hodgkin's lymphoma (malignant lymphoma), or Waldenstrom's macroglobulinemia.

42. The method of claim 38, wherein the cancer is an abstract nucleophosmin (NPM1)-mutated acute myeloid leukemia ( / .<., NPMlmutacute myloid leukemia) or a rearranged mixed lineage (KMT2A-rearranged) leukemia (MLL-r).

43. The compound of any one of claims 1-34 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 35 or claim 36, for use in treating or preventing a disease caused by, or associated with, menin expression, activity, and / or function.

44. The compound of any one of claims 1-34 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 35 or claim 36, for use in treating or preventing cancer.

45. Use of the compound of any one of claims 1-34 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 35 or claim 36, for treating or preventing a disease caused by, or associated with, menin expression, activity, and / or function.Attorney Docket No.: SYND-068 / 001WO 43707-0299746. Use of the compound of any one of claims 1-34 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 35 or claim 36, in the manufacture of a medicament for treating or preventing a disease caused by, or associated with, menin expression, activity, and / or function.

47. Use of a compound of any of claims 1-34 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 35 or claim 36, for treating or preventing cancer.

48. Use of the compound of any one of claims 1-34 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 35 or claim 36, in the manufacture of a medicament for treating or preventing cancer.

49. A kit comprising the compound of any one of claims 1-34 or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition of claim 35 or claim 36 and instructions for its use.

50. A method of preparing a compound herein according to a scheme of the present disclosure or synthetic description in the Examples.

51. An intermediate useful in the preparation of any one of the compounds herein.

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