Heterocyclic compounds as modulators of TNFα activity

Abstract

The present application provides heterocyclic compounds that modulate the activity of tumor necrosis factor-alpha (TNFα), which are useful in the treatment of various diseases, including autoimmune diseases and inflammatory diseases.

Description

[0001] 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0002] HETEROCYCLIC COMPOUNDS AS MODULATORS OF TNFa ACTIVITY

[0003] TECHNICAL FIELD

[0004] The present disclosure provides heterocyclic compounds as well as their pharmaceutical compositions that modulate the activity of tumor necrosis factor-alpha (TNFa) and are useful in the treatment of various diseases related to TNFa, including autoimmune diseases and inflammatory diseases.

[0005] BACKGROUND

[0006] Tumor Necrosis Factor-alpha (TNF-a) is a pro-inflammatory cytokine primarily produced by monocytes and macrophages. It plays a key role in the regulation of immune cells, inflammation, and apoptosis (see e.g., Nat. Rev. Rheumatol. 2016;12(l):49-62). TNF-a functions by binding to its receptors, TNFR1 and TNFR2, which activate multiple signaling pathways including NF-KB, MAPKS, and apoptotic pathways (see e.g., Physiol. Rev. 2019;99(l): 115-160). These pathways lead to the production of other cytokines, chemokines, and adhesion molecules, amplifying the inflammatory response.

[0007] SUMMARY

[0008] The present disclosure provides, inter alia, compounds of Formula I: or pharmaceutically acceptable salts thereof, wherein constituent members are defined herein.

[0009] The present disclosure further provides a pharmaceutical composition comprising a compound of the disclosure, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

[0010] The present disclosure further provides methods of inhibiting tumor necrosis factoralpha (TNFa) activity, comprising contacting the TNFa with a compound described herein, or a pharmaceutically acceptable salt thereof. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0011] The present disclosure further provides methods of treating a disease or a disorder associated with TNFa in a patient by administering to the patient a therapeutically effective amount of a compound of the disclosure, or a pharmaceutically acceptable salt thereof.

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

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

[0014] DETAILED DESCRIPTION

[0015] The present application provides a compound of Formula I:

[0016] I or a pharmaceutically acceptable salt thereof, wherein: m is 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, 4, 5, or 6; q is 0, 1, 2, 3, or, 4; r is 0, 1, 2, 3, or, 4; t is 0, 1, 2, 3, or, 4; provided that the sum of r and t is not 0;

[0017] Z1is N or CR3;

[0018] Z2is N or CR4;

[0019] X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;

[0020] Y1is N or CR5;

[0021] Y2is N or CR6;

[0022] Y3is N or CR7;

[0023] Ring A is C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl;

[0024] Ring B is a 5-membered heteroaryl; 54057 -0028 WO 1 / SNV0021-W01 PATENT each L1, L2, L3, and L4are independently selected from Ci-e alkylene, C2-6 alkenylene, C3-10 cycloalkylene, 4-10 membered heterocycloalkylene, phenylene, 5-10 membered heteroarylene, -O-, -S-, -N(RL2c)-, -C(O)-, -S(O)-, -S(O)2-, and -S(O)(=NRL2e)-, wherein the C1-6 alkylene, C2-6 alkenylene, C3-10 cycloalkylene, 4-10 membered heterocycloalkylene, phenylene, and 5-10 membered heteroarylene of L1, L2, L3, and L4are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; each RL2cis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2- e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORaL2, -NRcL2RdL2, -C(O)RaL2, -C(O)ORaL2, -C(O)NRcL2RdL2, -C(O)NRcL2(ORaL2), -S(O)RbL2, -S(O)2RbL2, - S(O)NRcL2RdL2, -S(O)2NRcL2RdL2, -S(O)(=NReL2)RbL2, -S(O)(=NReL2)NRcL2RdL2, - C(O)NRcL2S(O)2RbL2, -C(O)NRcL2S(O)2NRcL2RdL2, and -S(O)2NRcL2C(O)RbL2, wherein the Ci. e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RL2care each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; each RL2eis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RL2is independently selected from H, oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -Ci -4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORaL2, -SRaL2, -NRCL2RdL2 _n02-C(O)Rab2, -C(O)ORaL2, -C(O)NRcL2RdL2, -C(O)NRcL2(ORaL2), -OC(O)RaL2, -OC(O)NRcL2RdL2, -OC(O)ORaL2, -OS(O)2RbL2, -OS(O)2NRcL2RdL2, -NRcL2C(O)RaL2, - NRcL2C(O)ORaL2, -NRcL2C(O)NRcL2RdL2, -NRcL2S(O)2RbL2, -NRcL2S(O)2NRcL2RdL2, - NRcL2ORaL2, -NRcL2S(O)RbL2, -NRcL2S(O)NRcL2RdL2, -S(O)RbL2, -S(O)2RbL2, -S(O)NRcL2RdL2, -S(O)2NRcL2RdL2, -C(=NReL2)RaL2, -C(=NReL2)NRcL2RdL2, -NRcL2C(=NReL2)RaL2, - NRcL2C(=NReL2)NRcL2RdL2, -NRcL2S(O)(=NReL2)RbL2, -NRcL2S(O)(=NReL2)NRcL2RdL2, - OS(O)(=NReL2)RbL2, -S(O)(=NReL2)RbL2, -S(O)(=NReL2)NRcL2RdL2, -C(O)NRcL2S(O)2RbL2, - C(O)NRcL2S(O)2NRcL2RdL2, -S(O)2NRcL2C(O)RbL2, -NRcL2S(O)NRcL2C(O)RbL2, and - P(O)RfL2RgL2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, 54057 -0028 WO 1 / SNV0021-W01 PATENT phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci-4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of RL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RaL2, RcL2, and RdL2is independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -Ci -4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of RaL2, RcL2, and RdL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any RcL2and RdL2attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RbL2is independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl of RbL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each ReL2is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; each RlL2and RgL2are independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; each R1is independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-14 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-14 membered 54057 -0028 WO 1 / SNV0021-W01 PATENT heterocycloalkyl) -Ci .4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORal, -SRal, - NRclRdl, -NO2, -C(O)Ral, -C(O)ORal, -C(O)NRclRdl, -C(O)NRcl(ORal), -OC(O)Ral, - OC(O)NRclRdl, -OC(O)ORal, -OS(O)2Rbl, -OS(O)2NRclRdl, -NRclC(O)Ral, -NRclC(O)ORal, - NRclC(O)NRclRdl, -NRclS(O)2Rbl, -NRclS(O)2NRclRdl, -NRclORal, -NRclS(O)Rbl, - NRclS(O)NRclRdl, -S(O)Rbl, -S(O)2Rbl, -S(O)NRclRdl, -S(O)2NRclRdl, -C(=NRel)Ral, - C(=NRel)NRclRdl, -NRclC(=NRel)Ral, -NRclC(=NRel)NRclRdl, -NRclS(O)(=NRel)Rbl, - NRclS(O)(=NRel)NRclRdl, -OS(O)(=NRel)Rbl, -S(O)(=NRel)Rbl, -S(O)(=NRel)NRclRdl, - C(O)NRclS(O)2Rbl, -C(O)NRclS(O)2NRclRdl, -S(O)2NRclC(O)Rbl, -NRclS(O)NRclC(O)Rbl, and -P(O)RflRgl, wherein the Ci-e alkyl, C2.e alkenyl, C2.e alkynyl, Ci-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-14 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-14 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, two R1, together with the atoms to which they are attached to, form a C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, or 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ral, Rcl, and Rdlare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, any Rcland Rdlattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Rblis independently selected from Ci-e alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0025] (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rblare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Relis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each Rfland Rglare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R1Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, -SRalA, -NReiARdiA _N02-C(O)RalA, -C(O)ORalA, -C(O)NRclARdlA, -C(O)NRclA(ORalA), - OC(O)RalA, -OC(O)NRclARdlA, -OC(O)ORalA, -OS(O)2RblA, -OS(O)2NRclARdlA, - NRclAC(O)RalA, -NRclAC(O)ORalA, -NRclAC(O)NRclARdlA, -NRclAS(O)2RblA, - NRclAS(O)2NRclARdlA, -NRclAORalA, -NRclAS(O)RblA, -NRclAS(O)NRclARdlA, -S(O)RblA, - S(O)2RblA, -S(O)NRclARdlA, -S(O)2NRclARdlA, -C(=NRelA)RalA, -C(=NRelA)NRclARdlA, - NRclAC(=NRelA)RalA, -NRclAC(=NRelA)NRclARdlA, -NRclAS(O)(=NRelA)RblA, - NRclAS(O)(=NRelA)NRclARdlA, -OS(O)(=NRelA)RblA, -S(O)(=NRelA)RblA, - S(O)(=NRelA)NRclARdlA, -C(O)NRclAS(O)2RblA, -C(O)NRclAS(O)2NRclARdlA, - S(O)2NRclAC(O)RblA, -NRclAS(O)NRclAC(O)RblA, and -P(O)RflARglA, wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered 54057 -0028 WO 1 / SNV0021-W01 PATENT heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RalA, RclA, and RdlAare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Bsubstituents; or, any RclAand RdlAattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Bsubstituents; each RblAis independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RblAare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Bsubstituents; each RelAis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RflAand RglAare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R1Bis independently selected from oxo, H, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalB, -SRalB, -NReiBRdiB _NO2-C(O)RalB, -C(O)ORalB, -C(O)NRclBRdlB, -C(O)NRclB(ORalB), -OC(O)RalB, -OC(O)NRclBRdlB, -OC(O)ORalB, -OS(O)2RblB, -OS(O)2NRclBRdlB, -NRclBC(O)RalB, - NRclBC(O)ORalB, -NRclBC(O)NRclBRdlB, -NRclBS(O)2RblB, -NRclBS(O)2NRclBRdlB, - NRclBORalB, -NRclBS(O)RblB, -NRclBS(O)NRclBRdlB, -S(O)RblB, -S(O)2RblB, -S(O)NRclBRdlB, -S(O)2NRclBRdlB, -C(=NRelB)RalB, -C(=NRelB)NRclBRdlB, -NRclBC(=NRelB)RalB, - 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0026] NRclBC(=NRelB)NRclBRdlB, -NRclBS(O)(=NRelB)RblB, -NRclBS(O)(=NRelB)NRclBRdlB, - OS(O)(=NRelB)RblB, -S(O)(=NRelB)RblB, -S(O)(=NRelB)NRclBRdlB, -C(O)NRclBS(O)2RblB, - C(O)NRclBS(O)2NRclBRdlB, -S(O)2NRclBC(O)RblB, -NRclBS(O)NRclBC(O)RblB, and - P(O)RflBRglB, wherein the Ci-e alkyl, C2.e alkenyl, C2.e alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R1Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RalB, RclB, and RdlBis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RalB, RclB, and RdlBare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any RclBand RdlBattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RblBis independently selected from Ci-e alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RblBare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RelBis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; 54057 -0028 WO 1 / SNV0021-W01 PATENT each RflBand RglBare independently selected from H, Ci-e alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0027] R20is selected from C2-6 alkenyl, C2-6 alkynyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C2-6 alkenyl, C2-6 alkynyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents; each R2is independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, -SRa2, - NRc2Rd2, -NO2, -C(O)Ra2, -C(O)ORa2, -C(O)NRc2Rd2, -C(O)NRc2(ORa2), -OC(O)Ra2, - OC(O)NRc2Rd2, -OC(O)ORa2, -OS(O)2Rb2, -OS(O)2NRc2Rd2, -NRc2C(O)Ra2, -NRc2C(O)ORa2, - NRc2C(O)NRc2Rd2, -NRc2S(O)2Rb2, -NRc2S(O)2NRc2Rd2, -NRc2ORa2, -NRc2S(O)Rb2, - NRc2S(O)NRc2Rd2, -S(O)Rb2, -S(O)2Rb2, -S(O)NRc2Rd2, -S(O)2NRc2Rd2, -C(=NRe2)Ra2, - C(=NRe2)NRc2Rd2, -NRc2C(=NRe2)Ra2, -NRc2C(=NRe2)NRc2Rd2, -NRc2S(O)(=NRe2)Rb2, - NRc2S(O)(=NRe2)NRc2Rd2, -OS(O)(=NRe2)Rb2, -S(O)(=NRe2)Rb2, -S(O)(=NRe2)NRc2Rd2, - C(O)NRc2S(O)2Rb2, -C(O)NRc2S(O)2NRc2Rd2, -S(O)2NRc2C(O)Rb2, -NRc2S(O)NRc2C(O)Rb2, and -P(O)Rf2Rg2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra2, Rc2, and Rd2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; 54057 -0028 WO 1 / SNV0021-W01 PATENT or, any Rc2and Rd2atached to the same N atom, together with the N atom to which they are atached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Rb2is independently selected from Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Re2is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RQand Rg2are independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R2Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2A, -SRa2A, - S(O)2NRc2AC(O)Rb2A, -NRc2AS(O)NRc2AC(O)Rb2A, and -P(O)R£2ARg2A, wherein the Ci-6alkyl, 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0028] C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Bsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra2A, Rc2A, and Rd2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Bsubstituents; or, any Rc2Aand Rd2Aattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Bsubstituents; each Rb2Ais independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Bsubstituents; each Re2Ais independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RQAand Rg2Aare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0029] Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R2Bis independently selected from oxo, H, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2B, -SRa2B, -NRC2BRd2B _n02-C(O)Ra2B, -C(O)ORa2B, -C(O)NRc2BRd2B, -C(O)NRc2B(ORa2B), -OC(O)Ra2B, -OC(O)NRc2BRd2B, -OC(O)ORa2B, -OS(O)2Rb2B, -OS(O)2NRc2BRd2B, -NRc2BC(O)Ra2B, - NRc2BC(O)ORa2B, -NRc2BC(O)NRc2BRd2B, -NRc2BS(O)2Rb2B, -NRc2BS(O)2NRc2BRd2B, - NRc2BORa2B, -NRc2BS(O)Rb2B, -NRc2BS(O)NRc2BRd2B, -S(O)Rb2B, -S(O)2Rb2B, -S(O)NRc2BRd2B, -S(O)2NRc2BRd2B, -C(=NRe2B)Ra2B, -C(=NRe2B)NRc2BRd2B, -NRc2BC(=NRe2B)Ra2B, - NRc2BC(=NRe2B)NRc2BRd2B, -NRc2BS(O)(=NRe2B)Rb2B, -NRc2BS(O)(=NRe2B)NRc2BRd2B, - OS(O)(=NRe2B)Rb2B, -S(O)(=NRe2B)Rb2B, -S(O)(=NRe2B)NRc2BRd2B, -C(O)NRc2BS(O)2Rb2B, - C(O)NRc2BS(O)2NRc2BRd2B, -S(O)2NRc2BC(O)Rb2B, -NRc2BS(O)NRc2BC(O)Rb2B, and - P(O)Rf2BRg2B, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R2Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Ra2B, Rc2B, and Rd2Bis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra2B, Rc2B, and Rd2Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any Rc2Band Rd2Battached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Rb2Bis independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 54057 -0028 WO 1 / SNV0021-W01 PATENT alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb2Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Re2Bis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RQBand Rg2Bare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0030] R3and R4are independently selected from H, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa3, -SRa3, - NRc3Rd3, -NO2, -C(O)Ra3, -C(O)ORa3, -C(O)NRc3Rd3, -C(O)NRc3(ORa3), -OC(O)Ra3, - OC(O)NRc3Rd3, -OC(O)ORa3, -OS(O)2Rb3, -OS(O)2NRc3Rd3, -NRc3C(O)Ra3, -NRc3C(O)ORa3, - NRc3C(O)NRc3Rd3, -NRc3S(O)2Rb3, -NRc3S(O)2NRc3Rd3, -NRc3ORa3, -NRc3S(O)Rb3, - NRc3S(O)NRc3Rd3, -S(O)Rb3, -S(O)2Rb3, -S(O)NRc3Rd3, -S(O)2NRc3Rd3, -C(=NRe3)Ra3, - C(=NRe3)NRc3Rd3, -NRc3C(=NRe3)Ra3, -NRc3C(=NRe3)NRc3Rd3, -NRc3S(O)(=NRe3)Rb3, - NRc3S(O)(=NRe3)NRc3Rd3, -OS(O)(=NRe3)Rb3, -S(O)(=NRe3)Rb3, -S(O)(=NRe3)NRc3Rd3, - C(O)NRc3S(O)2Rb3, -C(O)NRc3S(O)2NRc3Rd3, -S(O)2NRc3C(O)Rb3, -NRc3S(O)NRc3C(O)Rb3, and -P(O)Rf3Rg3, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R3and R4are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, R3and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; 54057 -0028 WO 1 / SNV0021-W01 PATENT or, R3and one of L1, together with the atoms to which they are attached to, form a Cs- io cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, R4and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, R4and one of L2, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Ra3, Rc3, and Rd3is independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -Ci -4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of Ra3, Rc3, and Rd3are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any Rc3and Rd3attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Rb3is independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl of Rb3are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Re3is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; 54057 -0028 WO 1 / SNV0021-W01 PATENT each R° and Rg3are independently selected from H, Ci-e alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl;

[0031] R5is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl;

[0032] R6is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl;

[0033] R7is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl; and each RGis independently selected from H, OH, CN, halo, oxo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino; provided that when t is 0, Z1is CR3, Z2is CR4, and (L3)ris -CH2-, then:

[0034] (i) R3and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or

[0035] (ii) R3and one of L1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or

[0036] (iii) R4and one of R1, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or

[0037] (iv) R4and one of L2, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 54057 -0028 WO 1 / SNV0021-W01 PATENT membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

[0038] In some embodiments: m is 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, 4, 5, or 6; q is 0, 1, 2, 3, or, 4; r is 0, 1, 2, 3, or, 4; t is 0, 1, 2, 3, or, 4; provided that the sum of r and t is not 0;

[0039] Z1is N or CR3;

[0040] Z2is N or CR4;

[0041] X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;

[0042] Y1is N or CR5;

[0043] Y2is N or CR6;

[0044] Y3is N or CR7;

[0045] Ring A is C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl;

[0046] Ring B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from C1-6 alkylene, C2-6 alkenylene, C3-10 cycloalkylene, 4-10 membered heterocycloalkylene, phenylene, 5-10 membered heteroarylene, -O-, -S-, -N(RL2c)-, -C(O)-, -S(O)-, -S(O)2-, and -S(O)(=NRL2e)-, wherein the C1-6 alkylene, C2-6 alkenylene, C3-10 cycloalkylene, 4-10 membered heterocycloalkylene, phenylene, and 5-10 membered heteroarylene of L1, L2, L3, and L4are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; each RL2cis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2- e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1.4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORaL2, -NRcL2RdL2, -C(O)RaL2, -C(O)ORaL2, -C(O)NRcL2RdL2, -C(O)NRcL2(ORaL2), -S(O)RbL2, -S(O)2RbL2, - S(O)NRcL2RdL2, -S(O)2NRcL2RdL2, -S(O)(=NReL2)RbL2, -S(O)(=NReL2)NRcL2RdL2, - C(O)NRcL2S(O)2RbL2, -C(O)NRcL2S(O)2NRcL2RdL2, and -S(O)2NRcL2C(O)RbL2, wherein the Ci. e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RL2care each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; 54057 -0028 WO 1 / SNV0021-W01 PATENT each RL2eis independently selected from H, OH, CN, Ci-e alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RL2is independently selected from H, oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -Ci -4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORaL2, -SRaL2, -NRCL2RdL2 _n02-C(O)Rab2, -C(O)ORaL2, -C(O)NRcL2RdL2, -C(O)NRcL2(ORaL2), -OC(O)RaL2, -OC(O)NRcL2RdL2, -OC(O)ORaL2, -OS(O)2RbL2, -OS(O)2NRcL2RdL2, -NRcL2C(O)RaL2, - NRcL2C(O)ORaL2, -NRcL2C(O)NRcL2RdL2, -NRcL2S(O)2RbL2, -NRcL2S(O)2NRcL2RdL2, - NRcL2ORaL2, -NRcL2S(O)RbL2, -NRcL2S(O)NRcL2RdL2, -S(O)RbL2, -S(O)2RbL2, -S(O)NRcL2RdL2, -S(O)2NRcL2RdL2, -C(=NReL2)RaL2, -C(=NReL2)NRcL2RdL2, -NRcL2C(=NReL2)RaL2, - NRcL2C(=NReL2)NRcL2RdL2, -NRcL2S(O)(=NReL2)RbL2, -NRcL2S(O)(=NReL2)NRcL2RdL2, - OS(O)(=NReL2)RbL2, -S(O)(=NReL2)RbL2, -S(O)(=NReL2)NRcL2RdL2, -C(O)NRcL2S(O)2RbL2, - C(O)NRcL2S(O)2NRcL2RdL2, -S(O)2NRcL2C(O)RbL2, -NRcL2S(O)NRcL2C(O)RbL2, and - P(O)RfL2RgL2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci-4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of RL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RaL2, RcL2, and RdL2is independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -Ci -4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of RaL2, RcL2, and RdL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any RcL2and RdL2attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; 54057 -0028 WO 1 / SNV0021-W01 PATENT each RbL2is independently selected from Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl of RbL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each ReL2is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; each RlL2and RgL2are independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; each R1is independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORal, -SRal, - NRclRdl, -NO2, -C(O)Ral, -C(O)ORal, -C(O)NRclRdl, -C(O)NRcl(ORal), -OC(O)Ral, - OC(O)NRclRdl, -OC(O)ORal, -OS(O)2Rbl, -OS(O)2NRclRdl, -NRclC(O)Ral, -NRclC(O)ORal, - NRclC(O)NRclRdl, -NRclS(O)2Rbl, -NRclS(O)2NRclRdl, -NRclORal, -NRclS(O)Rbl, - NRclS(O)NRclRdl, -S(O)Rbl, -S(O)2Rbl, -S(O)NRclRdl, -S(O)2NRclRdl, -C(=NRel)Ral, - C(=NRel)NRclRdl, -NRclC(=NRel)Ral, -NRclC(=NRel)NRclRdl, -NRclS(O)(=NRel)Rbl, - NRclS(O)(=NRel)NRclRdl, -OS(O)(=NRel)Rbl, -S(O)(=NRel)Rbl, -S(O)(=NRel)NRclRdl, - C(O)NRclS(O)2Rbl, -C(O)NRclS(O)2NRclRdl, -S(O)2NRclC(O)Rbl, -NRclS(O)NRclC(O)Rbl, and -P(O)RflRgl, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, two R1, together with the atoms to which they are attached to, form a C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, or 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; 54057 -0028 WO 1 / SNV0021-W01 PATENT each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ral, Rcl, and Rdlare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, any Rcland Rdlattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Rblis independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rblare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Relis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each Rfland Rglare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R1Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, -SRalA, - 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0047] NReiARdiA _N02-C(O)RalA, -C(O)ORalA, -C(O)NRclARdlA, -C(O)NRclA(ORalA), - OC(O)RalA, -OC(O)NRclARdlA, -OC(O)ORalA, -OS(O)2RblA, -OS(O)2NRclARdlA, - NRclAC(O)RalA, -NRclAC(O)ORalA, -NRclAC(O)NRclARdlA, -NRclAS(O)2RblA, - NRclAS(O)2NRclARdlA, -NRclAORalA, -NRclAS(O)RblA, -NRclAS(O)NRclARdlA, -S(O)RblA, - S(O)2RblA, -S(O)NRclARdlA, -S(O)2NRclARdlA, -C(=NRelA)RalA, -C(=NRelA)NRclARdlA, - NRclAC(=NRelA)RalA, -NRclAC(=NRelA)NRclARdlA, -NRclAS(O)(=NRelA)RblA, - NRclAS(O)(=NRelA)NRclARdlA, -OS(O)(=NRelA)RblA, -S(O)(=NRelA)RblA, - S(O)(=NRelA)NRclARdlA, -C(O)NRclAS(O)2RblA, -C(O)NRclAS(O)2NRclARdlA, - S(O)2NRclAC(O)RblA, -NRclAS(O)NRclAC(O)RblA, and -P(O)RflARglA, wherein the Ci-6alkyl, C2-6 alkenyl, C2.e alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RalA, RclA, and RdlAare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any RclAand RdlAattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RblAis independently selected from Ci-e alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RblAare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; 54057 -0028 WO 1 / SNV0021-W01 PATENT each RelAis independently selected from H, OH, CN, Ci-e alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RflAand RglAare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0048] R20is selected from C2-6 alkenyl, C2-6 alkynyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C2-6 alkenyl, C2-6 alkynyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents; each R2is independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, -SRa2, - NRc2Rd2, -NO2, -C(O)Ra2, -C(O)ORa2, -C(O)NRc2Rd2, -C(O)NRc2(ORa2), -OC(O)Ra2, - OC(O)NRc2Rd2, -OC(O)ORa2, -OS(O)2Rb2, -OS(O)2NRc2Rd2, -NRc2C(O)Ra2, -NRc2C(O)ORa2, - NRc2C(O)NRc2Rd2, -NRc2S(O)2Rb2, -NRc2S(O)2NRc2Rd2, -NRc2ORa2, -NRc2S(O)Rb2, - NRc2S(O)NRc2Rd2, -S(O)Rb2, -S(O)2Rb2, -S(O)NRc2Rd2, -S(O)2NRc2Rd2, -C(=NRe2)Ra2, - C(=NRe2)NRc2Rd2, -NRc2C(=NRe2)Ra2, -NRc2C(=NRe2)NRc2Rd2, -NRc2S(O)(=NRe2)Rb2, - NRc2S(O)(=NRe2)NRc2Rd2, -OS(O)(=NRe2)Rb2, -S(O)(=NRe2)Rb2, -S(O)(=NRe2)NRc2Rd2, - C(O)NRc2S(O)2Rb2, -C(O)NRc2S(O)2NRc2Rd2, -S(O)2NRc2C(O)Rb2, -NRc2S(O)NRc2C(O)Rb2, and -P(O)Rf2Rg2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered 54057 -0028 WO 1 / SNV0021-W01 PATENT heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra2, Rc2, and Rd2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; or, any Rc2and Rd2attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Rb2is independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Re2is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RQand Rg2are independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R2Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2A, -SRa2A, - 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0049] NRc2AC(=NRe2A)Ra2A, -NRc2AC(=NRe2A)NRc2ARd2A, -NRc2AS(O)(=NRe2A)Rb2A, - NRc2AS(O)(=NRe2A)NRc2ARd2A, -OS(O)(=NRe2A)Rb2A, -S(O)(=NRe2A)Rb2A, - S(O)(=NRe2A)NRc2ARd2A, -C(O)NRc2AS(O)2Rb2A, -C(O)NRc2AS(O)2NRc2ARd2A, - S(O)2NRc2AC(O)Rb2A, -NRc2AS(O)NRc2AC(O)Rb2A, and -P(O)RQAR82A, wherein the Ci-6alkyl, C2-6 alkenyl, C2.e alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra2A, Rc2A, and Rd2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any Rc2Aand Rd2Aattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Rb2Ais independently selected from Ci-e alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Re2Ais independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; 54057 -0028 WO 1 / SNV0021-W01 PATENT each RQAand Rg2Aare independently selected from H, Ci-e alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;

[0050] R3and R4are independently selected from H, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -Ci -4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa3, -SRa3, - NRc3Rd3, -NO2, -C(O)Ra3, -C(O)ORa3, -C(O)NRc3Rd3, -C(O)NRc3(ORa3), -OC(O)Ra3, - OC(O)NRc3Rd3, -OC(O)ORa3, -OS(O)2Rb3, -OS(O)2NRc3Rd3, -NRc3C(O)Ra3, -NRc3C(O)ORa3, - NRc3C(O)NRc3Rd3, -NRc3S(O)2Rb3, -NRc3S(O)2NRc3Rd3, -NRc3ORa3, -NRc3S(O)Rb3, - NRc3S(O)NRc3Rd3, -S(O)Rb3, -S(O)2Rb3, -S(O)NRc3Rd3, -S(O)2NRc3Rd3, -C(=NRe3)Ra3, - C(=NRe3)NRc3Rd3, -NRc3C(=NRe3)Ra3, -NRc3C(=NRe3)NRc3Rd3, -NRc3S(O)(=NRe3)Rb3, - NRc3S(O)(=NRe3)NRc3Rd3, -OS(O)(=NRe3)Rb3, -S(O)(=NRe3)Rb3, -S(O)(=NRe3)NRc3Rd3, - C(O)NRc3S(O)2Rb3, -C(O)NRc3S(O)2NRc3Rd3, -S(O)2NRc3C(O)Rb3, -NRc3S(O)NRc3C(O)Rb3, and -P(O)Rf3Rg3, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R3and R4are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, R3and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, R3and one of L1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, R4and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, R4and one of L2, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 54057 -0028 WO 1 / SNV0021-W01 PATENT membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Ra3, Rc3, and Rd3is independently selected from H, Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -Ci -4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of Ra3, Rc3, and Rd3are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any Rc3and Rd3attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Rb3is independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl of Rb3are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Re3is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; each R° and Rg3are independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl;

[0051] R5is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl;

[0052] R6is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl;

[0053] R7is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl; and 54057 -0028 WO 1 / SNV0021-W01 PATENT each RGis independently selected from H, OH, CN, halo, oxo, Ci-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino; provided that when t is 0, Z1is CR3, Z2is CR4, and (L3)ris -CH2-, then:

[0054] (i) R3and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or

[0055] (ii) R3and one of L1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or

[0056] (iii) R4and one of R1, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or

[0057] (iv) R4and one of L2, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

[0058] In some embodiments, X1is C.

[0059] In some embodiments, X1is N.

[0060] In some embodiments, X2is N.

[0061] In some embodiments, X2is C.

[0062] In some embodiments, X3is C.

[0063] In some embodiments, X3is N.

[0064] In some embodiments, X4is C.

[0065] In some embodiments, X4is N.

[0066] In some embodiments: 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0067] X1is C;

[0068] X2is N;

[0069] X3is C; and

[0070] X4is C.

[0071] In some embodiments, Y1is N.

[0072] In some embodiments, Y1is CR5.

[0073] In some embodiments, R5is selected from H and Ci-6 alkyl.

[0074] In some embodiments, R5is selected from H and C1-3 alkyl.

[0075] In some embodiments, R5is H.

[0076] In some embodiments, Y2is N.

[0077] In some embodiments, Y2is CR6.

[0078] In some embodiments, R6is selected from H, C1-6 alkyl, and halo.

[0079] In some embodiments, R6is selected from H and C1-6 alkyl.

[0080] In some embodiments, R6is selected from H, C1-3 alkyl, and halo.

[0081] In some embodiments, R6is selected from H and C1-3 alkyl.

[0082] In some embodiments, R6is selected from H and halo.

[0083] In some embodiments, R6is selected from H and fluoro.

[0084] In some embodiments, R6is halo.

[0085] In some embodiments, R6is fluoro.

[0086] In some embodiments, R6is H.

[0087] In some embodiments, Y3is N.

[0088] In some embodiments, Y3is CR7.

[0089] In some embodiments, R7is selected from H, C1-6 alkyl, and halo.

[0090] In some embodiments, R7is selected from H and C1-6 alkyl.

[0091] In some embodiments, R7is selected from H, C1-3 alkyl, and halo.

[0092] In some embodiments, R7is selected from H and C1-3 alkyl.

[0093] In some embodiments, R7is selected from H and halo.

[0094] In some embodiments, R7is selected from H and fluoro.

[0095] In some embodiments, R7is halo.

[0096] In some embodiments, R7is fluoro.

[0097] In some embodiments, R7is H.

[0098] In some embodiments:

[0099] Y1is CR5;

[0100] Y2is CR6; and

[0101] Y3is CR7.

[0102] In some embodiments: 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0103] Y1is CR5;

[0104] Y2is CR6;

[0105] Y3is CR7;

[0106] R5is selected from H and C1-3 alkyl;

[0107] R6is selected from H, C1-3 alkyl, and halo; and

[0108] R7is selected from H, C1-3 alkyl, and halo.

[0109] In some embodiments:

[0110] Y1is CR5;

[0111] Y2is CR6;

[0112] Y3is CR7;

[0113] R5is selected from H and C1-3 alkyl;

[0114] R6is selected from H and halo; and

[0115] R7is selected from H and halo.

[0116] In some embodiments:

[0117] Y1is CR5;

[0118] Y2is CR6;

[0119] Y3is CR7;

[0120] R5is selected from H and C1-3 alkyl;

[0121] R6is selected from H and C1-3 alkyl; and

[0122] R7is selected from H and C1-3 alkyl.

[0123] In some embodiments:

[0124] Y1is CH;

[0125] Y2is CR6; and

[0126] Y3is CR7;

[0127] R6is selected from H and fluoro; and

[0128] R7is selected from H and fluoro.

[0129] In some embodiments:

[0130] Y1is CH;

[0131] Y2is CF; and

[0132] Y3is CH.

[0133] In some embodiments:

[0134] Y1is CH;

[0135] Y2is CH; and

[0136] Y3is CF.

[0137] In some embodiments:

[0138] Y1is CH; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0139] Y2is CH; and

[0140] Y3is CH.

[0141] In some embodiments, Z1is N.

[0142] In some embodiments, Z1is CR3.

[0143] In some embodiments, R3is selected from H and Ci-6 alkyl.

[0144] In some embodiments, R3is selected from H and C1-3 alkyl.

[0145] In some embodiments, R3is H.

[0146] In some embodiments, Z1is N.

[0147] In some embodiments, Z2is CR4.

[0148] In some embodiments, R4is selected from H and C1-6 alkyl.

[0149] In some embodiments, R4is selected from H and C1-3 alkyl.

[0150] In some embodiments, R4is H.

[0151] In some embodiments:

[0152] Z1is CR3; and

[0153] Z2is CR4.

[0154] In some embodiments:

[0155] Z1is CH; and

[0156] Z2is CH.

[0157] In some embodiments:

[0158] Z1is CR3; and

[0159] Z2is N.

[0160] In some embodiments:

[0161] Z1is CH; and

[0162] Z2is N.

[0163] In some embodiments, q is 0, 1, or 2.

[0164] In some embodiments, q is 0 or 1.

[0165] In some embodiments, q is 0.

[0166] In some embodiments, r is 1, 2, or 3.

[0167] In some embodiments, r is 1 or 2.

[0168] In some embodiments, r is 1.

[0169] In some embodiments, each L3is independently selected from C1-6 alkylene.

[0170] In some embodiments, each L3is independently selected from C1-3 alkylene.

[0171] In some embodiments, each L3is -CH2-.

[0172] In some embodiments, r is 1 and L3is C1-6 alkylene.

[0173] In some embodiments, r is 1 and L3is C1-3 alkylene.

[0174] In some embodiments, r is 1 and L3is -CH2-. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0175] In some embodiments, t is 0, 1, or 2.

[0176] In some embodiments, t is 0 or 1.

[0177] In some embodiments, t is 0.

[0178] In some embodiments, t is 1.

[0179] In some embodiments, each L4is independently selected from Ci-e alkylene.

[0180] In some embodiments, each L4is independently selected from C1-3 alkylene.

[0181] In some embodiments, each L4is -CH2-.

[0182] In some embodiments, t is 1 and L4is C1-6 alkylene.

[0183] In some embodiments, t is 1 and L4is C1-3 alkylene.

[0184] In some embodiments, t is 1 and L4is -CH2-.

[0185] In some embodiments, p is 1, 2, or 3.

[0186] In some embodiments, p is 1 or 2.

[0187] In some embodiments, p is 1.

[0188] In some embodiments, p is 2.

[0189] In some embodiments, each L2is independently selected from C1-6 alkylene, -N(RL2c)- , and -C(O)-, wherein the C1-6 alkylene of L2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents.

[0190] In some embodiments, each L2is independently selected from C1-3 alkylene, -N(RL2c)- , and -C(O)-.

[0191] In some embodiments, each RL2cis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0192] In some embodiments, each RL2cis independently selected from H and C1-6 alkyl.

[0193] In some embodiments, each RL2cis independently selected from H and C1-3 alkyl.

[0194] In some embodiments, each RL2cis independently selected from H and methyl.

[0195] In some embodiments, each L2is independently selected from C1-6 alkylene, -N(RL2c)- , and -C(O)-, wherein the C1-6 alkylene of L2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; and each RL2cis independently selected from H and C1-6 alkyl.

[0196] In some embodiments, each L2is independently selected from C1-3 alkylene, -N(RL2c)- , and -C(O)-; and each RL2cis independently selected from H and C1-3 alkyl.

[0197] In some embodiments, p is 1 and L2is selected from C1-6 alkylene, -N(RL2c)-, and - C(O)-, wherein the C1-6 alkylene of L2is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents.

[0198] In some embodiments, p is 1 and L2is selected from C1-3 alkylene, -N(RL2c)-, and -

[0199] C(O)-. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0200] In some embodiments, p is 1 and L2is selected from Ci-e alkylene, -N(RL2c)-, and - C(O)-, wherein the Ci-e alkylene of L2is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; and

[0201] RL2cis selected from H and Ci-e alkyl.

[0202] In some embodiments, p is 1 and L2is selected from C1-3 alkylene, -N(RL2c)-, and - C(O)-; and

[0203] RL2cis selected from H and C1-6 alkyl.

[0204] In some embodiments, p is 2 and each L2is independently selected from C1-6 alkylene, -N(RL2c)-, and -C(O)-, wherein each C1-6 alkylene of L2is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents.

[0205] In some embodiments, p is 2 and each L2is independently selected from C1-3 alkylene, -N(RL2c)-, and -C(O)-.

[0206] In some embodiments, p is 2 and each L2is independently selected from C1-6 alkylene, -N(RL2c)-, and -C(O)-, wherein each C1-6 alkylene of L2is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; and each RL2cis independently selected from H and C1-6 alkyl.

[0207] In some embodiments, p is 2 and each L2is independently selected from C1-3 alkylene, -N(RL2c)-, and -C(O)-; and each RL2cis independently selected from H and C1-3 alkyl.

[0208] In some embodiments, each L2is independently selected from -CH2-, -NH-, -N CHs)- , and -C(O)-.

[0209] In some embodiments, p is 1 and L2is selected from -CH2-, -NH-, -N CHs)-, and - C(O)-.

[0210] In some embodiments, p is 2 and each L2is independently selected from -CH2-, -NH-, -N(CH3)-, and -C(O)-.

[0211] In some embodiments, R4and one of L2, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

[0212] In some embodiments, R4and one of L2, together with the atoms to which they are attached to, form a 4-10 membered heterocycloalkyl, which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

[0213] In some embodiments, R4and one of L2, together with the atoms to which they are attached to, form a 4-10 membered heterocycloalkyl.

[0214] In some embodiments, R4and one of L2, together with the atoms to which they are attached to, form a 4-7 membered heterocycloalkyl. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0215] In some embodiments, R4and one of L2, together with the atoms to which they are attached to, form a pyrrolidine ring.

[0216] In some embodiments, Ring A is C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, or 5-6 membered heteroaryl.

[0217] In some embodiments, Ring A is Ce-io aryl.

[0218] In some embodiments, Ring A is phenyl.

[0219] In some embodiments, m is 0, 1, 2, or 3.

[0220] In some embodiments, m is 0, 1, or 2.

[0221] In some embodiments, m is 0 or 1.

[0222] In some embodiments, m is 1, 2, or 3.

[0223] In some embodiments, m is 1 or 2.

[0224] In some embodiments, m is 1.

[0225] In some embodiments, m is 2.

[0226] In some embodiments, m is 3.

[0227] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

[0228] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0229] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

[0230] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered 54057 -0028 WO 1 / SNV0021-W01 PATENT heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0231] In some embodiments, each R1is independently selected from halo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; and each Ral, Rcl, and Rdlis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0232] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3 or 4 independently selected R1Asubstituents; and each Ral, Rcl, and Rdlis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0233] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-14 cycloalkyl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, and -ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-14 cycloalkyl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; and each Ralis independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

[0234] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-14 cycloalkyl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, and -ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; and each Ralis independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

[0235] In some embodiments, each R1Ais independently selected from oxo, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, - CN, -ORalA, and -NRclARdlA, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci.4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0236] In some embodiments, each R1Ais independently selected from oxo, Ci-6 alkyl, Ci-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, - CN, -ORalA, and -NRclARdlA, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents.

[0237] In some embodiments, each RalA, RclA, and RdlAis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl.

[0238] In some embodiments, each RalA, RclA, and RdlAis independently selected from H, C1-6 alkyl, and C3-10 cycloalkyl-Ci-4 alkyl.

[0239] In some embodiments, each RalA, RclA, and RdlAis independently selected from H, C1-6 alkyl, and C3-7 cycloalkyl-Ci.4 alkyl.

[0240] In some embodiments, each R1Ais independently selected from oxo, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, - CN, -ORalA, and -NRclARdlA, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci.4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1, 2, 3, or 4 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from each RalA, RclA, and RdlAis independently selected from H, C1-6 alkyl, and C3-10 cycloalkyl-Ci-4 alkyl.

[0241] In some embodiments, each R1Ais independently selected from oxo, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, - CN, -ORalA, and -NRclARdlA, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci.4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from each RalA, RclA, and RdlAis independently selected from H, C1-6 alkyl, and C3-10 cycloalkyl-Ci-4 alkyl.

[0242] In some embodiments, each R1Ais independently selected from oxo, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, - CN, -ORalA, and -NRclARdlA, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci.4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from H, C1-6 alkyl, and C3-7 cycloalkyl-Ci.4 alkyl. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0243] In some embodiments, each R1Bis independently selected from Ci-e alkyl, CN, and - C(O)NRclBRdlB, wherein the Ci-e alkyl of R1Bis optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0244] In some embodiments, each R1Bis independently selected from Ci-6 alkyl, CN, and - C(O)NRclBRdlB, wherein the Ci-6 alkyl of R1Bis optionally substituted with 1 or 2 independently selected RGsubstituents.

[0245] In some embodiments, each R1Bis independently selected from Ci-6 alkyl, CN, and - C(O)NRclBRdlB, wherein the Ci-6 alkyl of R1Bis optionally substituted with 1 RGsubstituent.

[0246] In some embodiments, each R1Bis independently selected from Ci-6 alkyl, CN, and - C(O)NRclBRdlB, wherein the Ci-6 alkyl of R1Bis optionally substituted with ORalB.

[0247] In some embodiments, each RalB, RclB, and RdlBis independently selected from H, Ci- e alkyl, and C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with CN.

[0248] In some embodiments, each RalB, RclB, and RdlBis independently selected from H, Ci- e alkyl, and C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0249] In some embodiments, each RalB, RclB, and RdlBis independently selected from H, Ci- e alkyl, and C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with 1 or 2 independently selected RGsubstituents.

[0250] In some embodiments, each RalB, RclB, and RdlBis independently selected from H, Ci- e alkyl, and C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with 1 RGsubstituent.

[0251] In some embodiments, each RalB, RclB, and RdlBis independently selected from H, Ci- e alkyl, and C3-7 cycloalkyl, wherein the C3-7 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0252] In some embodiments, each RalB, RclB, and RdlBis independently selected from H, Ci- e alkyl, and C3-7 cycloalkyl, wherein the C3-7 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with 1 or 2 independently selected RGsubstituents.

[0253] In some embodiments, each RalB, RclB, and RdlBis independently selected from H, Ci- e alkyl, and C3-7 cycloalkyl, wherein the C3-7 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with 1 RGsubstituent.

[0254] In some embodiments, each RalB, RclB, and RdlBis independently selected from H, Ci- e alkyl, and C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with CN. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0255] In some embodiments, each RalB, RclB, and RdlBis independently selected from H, Ci- e alkyl, and C3-7 cycloalkyl, wherein the C3-7 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with CN.

[0256] In some embodiments, each R1Bis independently selected from Ci-e alkyl, CN, and - C(O)NRclBRdlB, wherein the Ci-e alkyl of R1Bis optionally substituted with ORalB; and each RalB, RclB, and RdlBis independently selected from H, Ci-e alkyl, and C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with CN.

[0257] In some embodiments, each R1Ais independently selected from oxo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, - CN, -ORalA, and -NRclARdlA, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from H, C1-6 alkyl, and C3-7 cycloalkyl-Ci.4 alkyl; each R1Bis independently selected from C1-6 alkyl, CN, and -C(O)NRclBRdlB, wherein the C1-6 alkyl of R1Bis optionally substituted with ORalB; and each RalB, RclB, and RdlBis independently selected from H, C1-6 alkyl, and C3-7 cycloalkyl, wherein the C3-7 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with CN.

[0258] In some embodiments, each R1Ais independently selected from oxo, methyl, ethyl, difluoromethyl, cyano, hydroxy, methoxy, amino, pyridinylmethyl, cyclopropyl, cyclopropylmethyl, cyclopropylmethylamino, pyridinyl, , and pyrimidinyl, wherein the methyl, ethyl, pyridinylmethyl, cyclopropyl, cyclopropylmethyl, pyridinyl, and pyrimidinyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents; and each R1Bis independently selected from hydroxymethyl, cyano, cyclopropylaminocarbonyl, and (cyanocyclopropyl)aminocarbonyl.

[0259] In some embodiments, each R1is independently selected from fluoro, methyl, cyclopropyl, pyrrolidinyl, dihydropyridazinyl, oxazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, [l,2,4]triazolo[l,5-a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyrimidinyl, 6,7-dihydro-5H- pyrazolo[5,l-b][l,3]oxazinyl, 4,5,6,7-tetrahydropyrazolo[l,5-a]pyrimidinyl, 6,7-dihydro- [ 1 ,2,4]triazolo [1,5 -a]pyrimidin-5 (4H)-onyl, 6,7-dihydropyrazolo [1,5 -a]pyrimidin-5 (4H)-onyl, 6,7-dihydropyrazolo[l,5-a]pyrazin-4(5H)-onyl, and difluoromethoxy, wherein the methyl, cyclopropyl, pyrrolidinyl, dihydropyridazinyl, oxazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, [l,2,4]triazolo[l,5-a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyrimidinyl, 6,7-dihydro-5H- pyrazolo[5,l-b][l,3]oxazinyl, 4,5,6,7-tetrahydropyrazolo[l,5-a]pyrimidinyl, 6,7-dihydro- 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0260] [ 1 ,2,4]triazolo [1,5 -a]pyrimidin-5 (4H)-onyl, 6,7-dihydropyrazolo [1,5 -a]pyrimidin-5 (4H)-onyl, and 6,7-dihydropyrazolo[l,5-a]pyrazin-4(5H)-onyl, of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents independently selected from oxo, methyl, ethyl, difluoromethyl, cyano, hydroxy, methoxy, amino, pyridinylmethyl, cyclopropyl, cyclopropylmethyl, (cyanocyclopropyl)methyl, cyclopropylmethylamino, cyanopyridinyl, (hydroxymethyl)pyridinyl, (cyclopropylaminocarbonyl)pyridinyl, (cyanocyclopropylaminocarbonyl)pyridinyl, and (cyclopropylaminocarbonyl)pyrimidinyl .

[0261] In some embodiments, each R1is independently selected from fluoro, methyl, hydroxymethyl, methoxymethyl, cyclopropyl, cyanopyrrolidinyl, methylpyridazin-3(2H)- onyl, methyloxazolyl, methylimidazolyl, pyrazolyl, methylpyrazolyl, ethylpyrazolyl, (amino)(methyl)pyrazolyl, (difluoromethyl)pyrazolyl, (pyridinylmethyl)pyrazolyl, methyltriazolyl, (amino)(methyl)triazolyl, methyltetrazolyl, difluoromethoxy, (cyclopropylmethyl)tetrazolyl, [ 1 ,2,4]triazolo [1,5 -a]pyrazinyl, [ 1 ,2,4]triazolo [1,5- a]pyrimidinyl, 6,7-dihydro-5H-pyrazolo[5,l-b][l,3]oxazinyl, 4,5,6,7-tetrahydropyrazolo[l,5- a]pyrimidinyl, 6,7-dihydro-[l,2,4]triazolo[l,5-a]pyrimidin-5(4H)-onyl, 6,7- dihydropyrazolo [ 1 ,5 -a]pyrimidin-5 (4H)-onyl, 5 -methyl-6,7-dihydropyrazolo [ 1 ,5 -a]pyrazin- 4(5H)-onyl, ((cyanocyclopropyl)methyl)pyrazolyl, (cyanopyridinyl)pyrazolyl, ((hydroxymethyl)pyridinyl)pyrazolyl, ((cyclopropylaminocarbonyl)pyrimidinyl)pyrazolyl, ((cyclopropylaminocarbonyl)pyridinyl)(amino)pyrazolyl, (((cyanocyclopropyl)aminocarbonyl)pyridinyl)pyrazolyl, ((cyclopropylmethyl)amino)(methyl)pyrazolyl, (cyanopyridinyl)triazolyl, ((cyclopropylaminocarbonyl)pyridinyl)triazolyl, (amino)(cyclopropyl)pyrazolyl, and ((cyanocyclopropyl)methyl)tetrazolyl.

[0262] In some embodiments, each R1is selected from fluoro, methyl, hydroxymethyl, methoxymethyl, difluoromethoxy, 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0263] In some embodiments, each R1is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

[0264] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0265] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 54057 -0028 WO 1 / SNV0021-W01 PATENT membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

[0266] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0267] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and - ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

[0268] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and - ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents.

[0269] In some embodiments, each R1Ais independently selected from oxo, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, (5-10 membered heteroaryl) -C 1.4 alkyl, -CN, -ORalA, and -NRclARdlA.

[0270] In some embodiments, each R1Ais independently selected from oxo, halo, C1-6 alkyl, C1-6 haloalkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA.

[0271] In some embodiments, each R1Ais independently selected from oxo, C1-6 alkyl, C1-6 haloalkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA.

[0272] In some embodiments, each RalA, RblA, RclA, and RdlAis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0273] In some embodiments, each RalA, RblA, RclA, and RdlAis independently selected from H and C1-6 alkyl.

[0274] In some embodiments, each RalA, RblA, RclA, and RdlAis independently selected from H and C1-3 alkyl. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0275] In some embodiments, each RalA, RclA, and RdlAis independently selected from H, Ci-6 alkyl, Ci-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0276] In some embodiments, each RalA, RclA, and RdlAis independently selected from H and Ci -e alkyl.

[0277] In some embodiments, each RalA, RclA, and RdlAis independently selected from H and C1-3 alkyl.

[0278] In some embodiments, each RalA, RclA, and RdlAis independently selected from H and methyl.

[0279] In some embodiments, each R1Ais independently selected from oxo, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, (5-10 membered heteroaryl) -C 1.4 alkyl, -CN, -ORalA, and -NRclARdlA; and each RalA, RclA, and RdlAis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0280] In some embodiments, each R1Ais independently selected from oxo, halo, C1-6 alkyl, C1-6 haloalkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA; and each RalA, RclA, and RdlAis independently selected from H and C1-6 alkyl.

[0281] In some embodiments, each R1Ais independently selected from oxo, C1-6 alkyl, C1-6 haloalkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA; and each RalA, RclA, and RdlAis independently selected from H and C1-6 alkyl.

[0282] In some embodiments, each R1Ais independently selected from oxo, methyl, ethyl, difluoromethyl, cyano, hydroxy, methoxy, amino, and pyridinylmethyl.

[0283] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORal, and -NRclRdl.

[0284] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, and -ORal.

[0285] In some embodiments, each R1is independently selected from -ORal.

[0286] In some embodiments, m is 1 and R1is selected from halo, C1-6 alkyl, C2-6 alkenyl, C2- e alkynyl, C1-6 haloalkyl, -CN, -ORal, and -NRclRdl.

[0287] In some embodiments, m is 1 and R1is selected from halo, C1-6 alkyl, C1-6 haloalkyl, and -ORal.

[0288] In some embodiments, m is 1 and R1is -ORal.

[0289] In some embodiments, each Ral, Rbl, Rcl, and Rdlis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0290] In some embodiments, each Ral, Rbl, Rcl, and Rdlis independently selected from H,

[0291] C1-6 alkyl, and C1-6 haloalkyl. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0292] In some embodiments, each Ral, Rbl, Rcl, and Rdlis independently selected from H, Ci -3 alkyl and C1-3 haloalkyl.

[0293] In some embodiments, each Ral, Rbl, Rcl, and Rdlis independently selected from Ci-e haloalkyl.

[0294] In some embodiments, each Ral, Rbl, Rcl, and Rdlis independently selected from C1-3 haloalkyl.

[0295] In some embodiments, each Ral, Rcl, and Rdlis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0296] In some embodiments, each Ral, Rcl, and Rdlis independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

[0297] In some embodiments, each Ral, Rcl, and Rdlis independently selected from H, C1-3 alkyl and C1-3 haloalkyl.

[0298] In some embodiments, each Ral, Rcl, and Rdlis independently selected from C1-6 haloalkyl.

[0299] In some embodiments, each Ral, Rcl, and Rdlis independently selected from C1-3 haloalkyl.

[0300] In some embodiments, each Ralis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0301] In some embodiments, each Ralis independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

[0302] In some embodiments, each Ralis independently selected from H, C1-3 alkyl and C1-3 haloalkyl.

[0303] In some embodiments, each Ralis independently selected from C1-6 haloalkyl.

[0304] In some embodiments, each Ralis independently selected from C1-3 haloalkyl.

[0305] In some embodiments, each Ralis independently selected from difluoromethyl.

[0306] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; and each Ral, Rcl, and Rdlis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0307] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 54057 -0028 WO 1 / SNV0021-W01 PATENT alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; and each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0308] In some embodiments, each R1is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; and each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0309] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; and each Ral, Rcl, and Rdlis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0310] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and - ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; and each Ralis independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

[0311] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and - ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; and each Ralis independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

[0312] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and - ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 54057 -0028 WO 1 / SNV0021-W01 PATENT and 5-6 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; each R1Ais independently selected from oxo, halo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NReiARdiA.andeach RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0313] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and - ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; each R1Ais independently selected from oxo, C1-6 alkyl, C1-6 haloalkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA; and each RalA, RclA, and RdlAis independently selected from H and C1-6 alkyl.

[0314] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and - ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; each R1Ais independently selected from oxo, methyl, ethyl, difluoromethyl, cyano, hydroxy, methoxy, amino, and pyridinylmethyl.

[0315] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORal, and -NRclRdl; and each Ral, Rcl, and Rdlis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0316] In some embodiments, each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, and -ORal; and each Ralis independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

[0317] In some embodiments, m is 1 and R1is selected from halo, C1-6 alkyl, C2-6 alkenyl, C2- e alkynyl, C1-6 haloalkyl, -CN, -ORal, and -NRclRdl; and

[0318] Ral, Rcl, and Rdlare each independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

[0319] In some embodiments, m is 1 and R1is selected from halo, C1-6 alkyl, C1-6 haloalkyl, and -ORal; and 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0320] Ralis selected from H, Ci-e alkyl, and Ci-6 haloalkyl.

[0321] In some embodiments, each R1is independently selected from fluoro, methyl, cyclopropyl, pyrrolidinyl, dihydropyridazinyl, oxazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and difluoromethoxy, wherein the methyl, cyclopropyl, pyrrolidinyl, dihydropyridazinyl, oxazolyl, imidazolyl, pyrazolyl, triazolyl, and tetrazolyl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents independently selected from oxo, methyl, ethyl, difluoromethyl, cyano, hydroxy, methoxy, amino, and pyridinylmethyl .

[0322] In some embodiments, each R1is independently selected from fluoro, methyl, cyclopropyl, pyrrolidinyl, dihydropyridazinyl, oxazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and difluoromethoxy, wherein the methyl, cyclopropyl, pyrrolidinyl, dihydropyridazinyl, oxazolyl, imidazolyl, pyrazolyl, triazolyl, and tetrazolyl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents independently selected from oxo, methyl, ethyl, difluoromethyl, cyano, hydroxy, methoxy, amino, and pyridinylmethyl .

[0323] In some embodiments, each R1is independently selected from fluoro, methyl, hydroxymethyl, methoxymethyl, cyclopropyl, cyanopyrrolidinyl, methylpyridazin-3(2H)- onyl, methyloxazolyl, methylimidazolyl, pyrazolyl, methylpyrazolyl, ethylpyrazolyl, (amino)(methyl)pyrazolyl, (difluoromethyl)pyrazolyl, (pyridinylmethyl)pyrazolyl, methyltriazolyl, methyltetrazolyl, and difluoromethoxy.

[0324] In some embodiments, each R1is selected from fluoro, methyl, hydroxymethyl,

[0325] In some embodiments, each R1is independently selected from difluoromethoxy.

[0326] In some embodiments, m is 1 and R1is difluoromethoxy.

[0327] In some embodiments, R20is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C3-14 cycloalkyl, Ce- 10 aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0328] In some embodiments, R20is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C3-14 cycloalkyl, Ce- 10 aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents.

[0329] In some embodiments, R20is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C3-14 cycloalkyl, Ce- 10 aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1 or 2 independently selected R2substituents.

[0330] In some embodiments, R20is selected from C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents.

[0331] In some embodiments, R20is selected from C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents.

[0332] In some embodiments, R20is selected from C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R20are each optionally substituted with 1 or 2 independently selected R2substituents.

[0333] In some embodiments, R20is selected from Ce-io aryl and 5-10 membered heteroaryl, wherein the Ce-io aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents.

[0334] In some embodiments, R20is selected from Ce-io aryl and 5-10 membered heteroaryl, wherein the Ce-io aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents.

[0335] In some embodiments, R20is selected from Ce-io aryl and 5-10 membered heteroaryl, wherein the Ce-io aryl and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 independently selected R2substituents.

[0336] In some embodiments, R20is selected from phenyl and 5-6 membered heteroaryl, wherein the phenyl and 5-6 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents.

[0337] In some embodiments, R20is selected from phenyl and 5-6 membered heteroaryl, wherein the phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 independently selected R2substituents. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0338] In some embodiments, R20is selected from phenyl, pyridinyl, and pyrimidinyl, wherein the phenyl, pyridinyl, and pyrimidinyl are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents.

[0339] In some embodiments, R20is selected from phenyl, pyridinyl, and pyrimidinyl, wherein the phenyl, pyridinyl, and pyrimidinyl are each optionally substituted with 1 or 2 independently selected R2substituents.

[0340] In some embodiments, each R2is independently selected from halo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, - ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci.4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents.

[0341] In some embodiments, each R2is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents.

[0342] In some embodiments, each R2is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, (5-10 membered heteroaryl) -C 1.4 alkyl, -CN, - ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents.

[0343] In some embodiments, each R2is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, (5-6 membered heteroaryl) -C 1.4 alkyl, -ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, or 4 independently selected R2Asubstituents.

[0344] In some embodiments, each R2is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0345] -ORa2, and -NRc2Rd2, wherein the Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R2are each optionally substituted with 1, 2, 3, or 4 independently selected R2Asubstituents.

[0346] In some embodiments, each Ra2, Rc2, and Rd2is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl.

[0347] In some embodiments, each Ra2, Rc2, and Rd2is independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

[0348] In some embodiments, each Ra2, Rc2, and Rd2is independently selected from H and C1-6 alkyl.

[0349] In some embodiments, each Ra2, Rc2, and Rd2is independently selected from H and C1.3 alkyl.

[0350] In some embodiments, each Ra2, Rc2, and Rd2is H.

[0351] In some embodiments, each R2is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, - ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci.4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; and each Ra2, Rc2, and Rd2is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl.

[0352] In some embodiments, each R2is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; and each Ra2, Rc2, and Rd2is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl.

[0353] In some embodiments, each R2is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, (5-10 membered heteroaryl) -C 1.4 alkyl, -CN, - ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, and (5-10 54057 -0028 WO 1 / SNV0021-W01 PATENT membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; and each Ra2, Rc2, and Rd2is independently selected from H and Ci-e alkyl.

[0354] In some embodiments, each R2is independently selected from halo, Ci-6 alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, (5-6 membered heteroaryl) -C 1.4 alkyl, -ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, or 4 independently selected R2Asubstituents; and each Ra2, Rc2, and Rd2is independently selected from H and C1-6 alkyl.

[0355] In some embodiments, each R2is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, -ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R2are each optionally substituted with 1, 2, 3, or 4 independently selected R2Asubstituents; and each Ra2, Rc2, and Rd2is independently selected from H and C1-6 alkyl.

[0356] In some embodiments, each R2is independently selected from fluoro, isopropyl, cyclobutyl, azabicyclo[3.1.0]hexanyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, imidazolidinyl, piperidinyl, pyrazolylethyl, and amino, wherein the isopropyl, cyclobutyl, azabicyclo[3.1.0]hexanyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, imidazolidinyl, piperidinyl, and pyrazolylethyl, are each optionally substituted with 1, 2, 3, or 4 independently selected R2Asubstituents.

[0357] In some embodiments, each R2is independently selected from fluoro, isopropyl, cyclobutyl, azabicyclo[3.1.0]hexanyl, and amino, wherein the isopropyl, cyclobutyl, and azabicyclo[3.1.0]hexanyl are each optionally substituted with 1, 2, 3, or 4 independently selected R2Asubstituents.

[0358] In some embodiments, each R2Ais independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6alkynyl, Ci-6haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, and C1-6 haloalkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents.

[0359] In some embodiments, each R2Ais independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6alkynyl, Ci-6haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the Ci-6 alkyl, C2-6 alkenyl, C2-e alkynyl, and Ci-6 haloalkyl of R2Aare each optionally substituted with 1 or 2 independently selected RGsubstituents. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0360] In some embodiments, each R2Ais independently selected from Ci-e alkyl, CN, - ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein each Ci-e alkyl of R2Ais optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents.

[0361] In some embodiments, each R2Ais independently selected from Ci-6 alkyl, CN, - ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein each Ci-6 alkyl of R2Ais optionally substituted with 1 or 2 independently selected RGsubstituents.

[0362] In some embodiments, each R2Ais independently selected from Ci-6 alkyl, CN, - ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein each Ci-6 alkyl of R2Ais optionally substituted with 1 RGsubstituent.

[0363] In some embodiments, each RGis independently selected from H, OH, CN, halo, oxo, Ci-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci-4 alkyl.

[0364] In some embodiments, each RGis independently selected from OH, CN, and halo.

[0365] In some embodiments, each RGis independently selected from OH.

[0366] In some embodiments, each R2Ais independently selected from C1-6 alkyl, CN, - ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein each C1-6 alkyl of R2Ais optionally substituted with OH.

[0367] In some embodiments, each R2Ais independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORa2A, and -NRc2ARd2A.

[0368] In some embodiments, each R2Ais independently selected from C1-6 alkyl, -ORa2A, and -NRc2ARd2A.

[0369] In some embodiments, each Ra2A, Rc2A, and Rd2Ais independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl.

[0370] In some embodiments, each Ra2A, Rc2A, and Rd2Ais independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

[0371] In some embodiments, each Ra2A, Rc2A, and Rd2Ais independently selected from H and C1-6 alkyl.

[0372] In some embodiments, each Ra2A, Rc2A, and Rd2Ais independently selected from H and C1-3 alkyl.

[0373] In some embodiments, each Ra2A, Rc2A, and Rd2Ais H.

[0374] In some embodiments, each R2Ais independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORa2A, and -NRc2ARd2A; and each Ra2A, Rc2A, and Rd2Ais independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl.

[0375] In some embodiments, each R2Ais independently selected from C1-6 alkyl, -ORa2A, and -NRc2ARd2A; and 54057 -0028 WO 1 / SNV0021-W01 PATENT each Ra2A, Rc2A, and Rd2Ais independently selected from H and Ci-e alkyl.

[0376] In some embodiments, each R2Ais independently selected from Ci-6 alkyl, -ORa2A, and -NRc2ARd2A; and each Ra2A, Rc2A, and Rd2Ais independently selected from H and C1-3 alkyl.

[0377] In some embodiments, each R2Ais independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6alkynyl, Ci-6haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, and C1-6 haloalkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; and each Ra2A, Rc2A, and Rd2Ais independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, and C1-6 haloalkyl.

[0378] In some embodiments, each R2Ais independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6alkynyl, Ci-6haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the Ci-6 alkyl, C2-6 alkenyl, C2-e alkynyl, and Ci-6 haloalkyl of R2Aare each optionally substituted with 1 or 2 independently selected RGsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H, Ci-6 alkyl, C2-6 alkenyl, C2-e alkynyl, and Ci-6 haloalkyl.

[0379] In some embodiments, each R2Ais independently selected from Ci-6 alkyl, CN, - ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein each Ci-6 alkyl of R2Ais optionally substituted with 1, 2, 3, or 4 independently selected RGsubstituents; and each Ra2A, Rc2A, and Rd2Ais independently selected from H and Ci-6 alkyl.

[0380] In some embodiments, each R2Ais independently selected from Ci-6 alkyl, CN, - ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein each Ci-6 alkyl of R2Ais optionally substituted with 1 or 2 independently selected RGsubstituents; and each Ra2A, Rc2A, and Rd2Ais independently selected from H and Ci-6 alkyl.

[0381] In some embodiments, each R2Ais independently selected from Ci-6 alkyl, CN, - ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein each Ci-6 alkyl of R2Ais optionally substituted with 1 RGsubstituent; and each Ra2A, Rc2A, and Rd2Ais independently selected from H and Ci-6 alkyl

[0382] In some embodiments, each R2Ais independently selected from methyl, hydroxymethyl, hydroxy, methoxy, cyano, amino, and -C(O)NH2.

[0383] In some embodiments, each R2Ais independently selected from methyl, hydroxy, and amino.

[0384] In some embodiments, each R2is independently selected from fluoro, hydroxyisopropyl, aminoisopropyl, dihydroxyisopropyl, (hydroxy)(methoxy)isopropyl, (cyano)(hydroxy)isopropyl, hydroxycyclobutyl, (cyano)(hydroxy)(methyl)cyclobutyl, (hydroxymethyl)cyclobutyl, (aminocarbonyl)cyclobutyl, dihydroxycyclobutyl, 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0385] (amino)(hydroxy)(methyl)cyclobutyl, (hydroxy)(hydroxymethyl)(methyl)cyclobutyl, (amino)(hydroxymethyl)(methyl)cyclobutyl, aminocyclobutyl, 3-methyl-3- azabicyclo[3.1.0]hexanyl, hydroxyoxetanyl, aminotetrahydrofuranyl, hydroxytetrahydrofuranyl, hydroxytetrahydropyranyl, methylimidazolidine-2,4-dionyl, hydroxypiperidinyl, (methylpyrazolyl)(hydroxy)ethyl, and amino.

[0386] In some embodiments, each R2is independently selected from fluoro, amino,

[0387] In some embodiments, each R2is independently selected from fluoro, amino,

[0388] In some embodiments, each R2is independently selected from fluoro, hydroxyisopropyl, aminocyclobutyl, 3-methyl-3-azabicyclo[3.1.0]hexanyl, and amino.

[0389] In some embodiments: m is 0, 1, 2, or 3; 54057 -0028 WO 1 / SNV0021-W01 PATENT p is 1, 2, 3, 4, or 5; q is 0 or 1; r is 1 or 2; t is 0 or 1;

[0390] Z1is N or CR3;

[0391] Z2is N or CR4;

[0392] X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;

[0393] Y1is CR5;

[0394] Y2is CR6;

[0395] Y3is CR7;

[0396] Ring A is C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, or 5-6 membered heteroaryl;

[0397] Ring B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from Ci-e alkylene, -N(RL2c)-, and - C(O)-; each RL2cis independently selected from H and Ci-e alkyl;

[0398] R20is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents; each R1is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R1Ais independently selected from oxo, Ci-e alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA, wherein the Ci-e alkyl, C1-6 haloalkyl, C 3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-io cycloalkyl-Ci-4 alkyl; 54057 -0028 WO 1 / SNV0021-W01 PATENT each R1Bis independently selected from Ci-e alkyl, CN, and -C(O)NRclBRdlB, wherein the Ci-6 alkyl of R1Bis optionally substituted with ORalB; each RalB, RclB, and RdlBis independently selected from H, Ci-e alkyl, and C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with CN; each R2is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, and - NRc2Rd2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce- 10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; each R2Ais independently selected from oxo, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0399] R3is selected from H and Ci-e alkyl;

[0400] R4is selected from H and Ci-e alkyl; or

[0401] R4and one of L2, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl;

[0402] R5is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0403] R6is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0404] R7is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy; and each RGis independently selected from H, OH, CN, halo, oxo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl.

[0405] In some embodiments: m is 0, 1, 2, or 3; 54057 -0028 WO 1 / SNV0021-W01 PATENT p is 1, 2, 3, 4, or 5; q is 0 or 1; r is 1 or 2; t is 0 or 1;

[0406] Z1is N or CR3;

[0407] Z2is N or CR4;

[0408] X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;

[0409] Y1is CR5;

[0410] Y2is CR6;

[0411] Y3is CR7;

[0412] Ring A is phenyl;

[0413] Ring B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from Ci-e alkylene, -N(RL2c)-, and - C(O)-; each RL2cis independently selected from H and Ci-e alkyl;

[0414] R20is selected from C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents; each R1is independently selected from halo, Ci-e alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, and -ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; each Ralis independently selected from H, Ci-e alkyl, and C1-6 haloalkyl; each R1Ais independently selected from oxo, Ci-e alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA, wherein the Ci-e alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, and C3-7 cycloalkyl-Ci-4 alkyl; each R1Bis independently selected from Ci-e alkyl, CN, and -C(O)NRclBRdlB, wherein the C1-6 alkyl of R1Bis optionally substituted with ORalB; 54057 -0028 WO 1 / SNV0021-W01 PATENT each RalB, RclB, and RdlBis independently selected from H, Ci-e alkyl, and C3-7 cycloalkyl, wherein the C3-7 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with CN; each R2is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, and - NRc2Rd2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce- 10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; each R2Ais independently selected from oxo, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H and Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0415] R3is selected from H and Ci-e alkyl;

[0416] R4is selected from H and Ci-e alkyl; or

[0417] R4and one of L2, together with the atoms to which they are attached to form a 4-7 membered heterocycloalkyl;

[0418] R5is selected from H and C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0419] R6is selected from H, Ci-e alkyl, and halo;

[0420] R7is selected from H, Ci-e alkyl, and halo; and each RGis independently selected from H, OH, CN, halo, oxo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl.

[0421] In some embodiments: m is 0, 1, 2, or 3; p is 1, 2, 3, 4, or 5; q is 0 or 1; r is 1 or 2; t is 0 or 1;

[0422] Z1is N or CR3; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0423] Z2is N or CR4;

[0424] X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;

[0425] Y1is CR5;

[0426] Y2is CR6;

[0427] Y3is CR7;

[0428] Ring A is C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, or 5-6 membered heteroaryl;

[0429] Ring B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from Ci-e alkylene, -N(RL2c)-, and - C(O)-; each RL2cis independently selected from H and Ci-e alkyl;

[0430] R20is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents; each R1is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R1Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRelARdlA. each RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R2is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, and - NRc2Rd2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce- 10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 54057 -0028 WO 1 / SNV0021-W01 PATENT alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; each R2Ais independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0431] R3is selected from H and Ci-e alkyl;

[0432] R4is selected from H and Ci-e alkyl; or

[0433] R4and one of L2, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl;

[0434] R5is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0435] R6is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0436] R7is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy; and each RGis independently selected from H, OH, CN, halo, oxo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl.

[0437] In some embodiments: m is 0, 1, 2, or 3; p is 1, 2, 3, 4, or 5; q is 0 or 1; r is 1 or 2; t is 0 or 1;

[0438] Z1is N or CR3;

[0439] Z2is N or CR4;

[0440] X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;

[0441] Y1is CR5;

[0442] Y2is CR6;

[0443] Y3is CR7; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0444] Ring A is phenyl;

[0445] Ring B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from Ci-e alkylene, -N(RL2c)-, and -

[0446] C(O)-; each RL2cis independently selected from H and Ci-e alkyl;

[0447] R20is selected from C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents; each R1is independently selected from halo, Ci-e alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and -ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R1Ais independently selected from oxo, Ci-e alkyl, C1-6 haloalkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA; each RalA, RclA, and RdlAis independently selected from H and Ci-e alkyl; each R2is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, and - NRc2Rd2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce- 10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; each R2Ais independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H and Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0448] R3is selected from H and Ci-e alkyl; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0449] R4is selected from H and Ci-e alkyl; or

[0450] R4and one of L2, together with the atoms to which they are attached to form a 4-7 membered heterocycloalkyl;

[0451] R5is selected from H and Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, and Ci-6 haloalkoxy;

[0452] R6is selected from H, Ci-e alkyl, and halo;

[0453] R7is selected from H, Ci-e alkyl, and halo; and each RGis independently selected from H, OH, CN, halo, oxo, Ci-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl.

[0454] In some embodiments: m is 0, 1, or 2; p is 1, 2, or 3; q is 0 or 1; r is 1 or 2; t is 0 or 1;

[0455] Z1is N or CR3;

[0456] Z2is N or CR4;

[0457] X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;

[0458] Y1is CR5;

[0459] Y2is CR6;

[0460] Y3is CR7;

[0461] Ring A is C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, or 5-6 membered heteroaryl;

[0462] Ring B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from C1-6 alkylene, -N(RL2c)-, and - C(O)-; each RL2cis independently selected from H and C1-6 alkyl;

[0463] R20is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents; each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORal, and -NRclRdl; each Ral, Rcl, and Rdlis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; 54057 -0028 WO 1 / SNV0021-W01 PATENT each R2is independently selected from halo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; each R2Ais independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORa2A, and -NRc2ARd2A; each Ra2A, Rc2A, and Rd2Ais independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0464] R3is selected from H and Ci-e alkyl;

[0465] R4is selected from H and Ci-e alkyl; or

[0466] R4and one of L2, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl;

[0467] R5is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0468] R6is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy; and

[0469] R7is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy.

[0470] In some embodiments: m is 0, 1, or 2; p is 1, 2, or 3; q is 0 or 1; r is 1 or 2; t is 0 or 1;

[0471] Z1is N or CR3;

[0472] Z2is N or CR4;

[0473] X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;

[0474] Y1is CR5;

[0475] Y2is CR6;

[0476] Y3is CR7;

[0477] Ring A is phenyl; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0478] Ring B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from Ci-e alkylene, -N(RL2c)-, and -

[0479] C(O)-; each RL2cis independently selected from H and Ci-e alkyl;

[0480] R20is selected from C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents; each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORal, and -NRclRdl; each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R2is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; each R2Ais independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORa2A, and -NRc2ARd2A; each Ra2A, Rc2A, and Rd2Ais independently selected from H and Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;

[0481] R3is selected from H and Ci-e alkyl;

[0482] R4is selected from H and Ci-e alkyl; or

[0483] R4and one of L2, together with the atoms to which they are attached to form a 4-7 membered heterocycloalkyl;

[0484] R5is selected from H and C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;

[0485] R6is selected from H and Ci-e alkyl; and

[0486] R7is selected from H and Ci-e alkyl.

[0487] In some embodiments, the compound of Formula I is a compound of Formula II: 54057 -0028 WO 1 / SNV0021-W01 PATENT or a pharmaceutically acceptable salt thereof.

[0488] In some embodiments, the compound of Formula I is a compound of Formula Ila: or a pharmaceutically acceptable salt thereof.

[0489] In some embodiments, the compound of Formula I is a compound of Formula III: or a pharmaceutically acceptable salt thereof.

[0490] In some embodiments, the compound of Formula I is a compound of Formula Illa: 54057 -0028 WO 1 / SNV0021-W01 PATENT or a pharmaceutically acceptable salt thereof.

[0491] In some embodiments, the compound of Formula I is a compound of Formula Illb: or a pharmaceutically acceptable salt thereof.

[0492] In some embodiments, the compound of Formula I is a compound of Formula IIIc:

[0493] IIIc or a pharmaceutically acceptable salt thereof.

[0494] In some embodiments, the compound of Formula I is a compound of Formula IV: 54057 -0028 WO 1 / SNV0021-W01 PATENT or a pharmaceutically acceptable salt thereof.

[0495] In some embodiments, the compound of Formula I is a compound of Formula IVa: or a pharmaceutically acceptable salt thereof.

[0496] In some embodiments, the compound of Formula I is a compound of Formula IVb: or a pharmaceutically acceptable salt thereof.

[0497] In some embodiments, the compound of Formula l is a compound of Formula V : 54057 -0028 WO 1 / SNV0021-W01 PATENT or a pharmaceutically acceptable salt thereof.

[0498] In some embodiments, the compound of Formula I is a compound of Formula Va:

[0499] Va or a pharmaceutically acceptable salt thereof.

[0500] In some embodiments, the compound of Formula I is a compound of Formula Vb: or a pharmaceutically acceptable salt thereof.

[0501] In some embodiments, the compound of Formula I is a compound of Formula Vc: 54057 -0028 WO 1 / SNV0021-W01 PATENT or a pharmaceutically acceptable salt thereof.

[0502] In some embodiments, the compound of Formula I is a compound of Formula VI: or a pharmaceutically acceptable salt thereof.

[0503] In some embodiments, the compound of Formula I is a compound of Formula Via: or a pharmaceutically acceptable salt thereof.

[0504] In some embodiments, the compound of Formula I is a compound of Formula VIb: 54057 -0028 WO 1 / SNV0021-W01 PATENT or a pharmaceutically acceptable salt thereof.

[0505] In some embodiments, the compound of Formula I is a compound of Formula Vic: or a pharmaceutically acceptable salt thereof.

[0506] In some embodiments, the compound of Formula I is a compound of Formula VII: or a pharmaceutically acceptable salt thereof.

[0507] In some embodiments, the compound of Formula I is a compound of Formula Vila: 54057 -0028 WO 1 / SNV0021-W01 PATENT or a pharmaceutically acceptable salt thereof.

[0508] In some embodiments, the compound of Formula I is a compound of Formula Vllb:

[0509] Vllb or a pharmaceutically acceptable salt thereof.

[0510] In some embodiments, the compound of Formula I is a compound of Formula Vile: 54057 -0028 WO 1 / SNV0021-W01 PATENT or a pharmaceutically acceptable salt thereof.

[0511] In some embodiments, the compound of Formula I is a compound of Formula VIII: or a pharmaceutically acceptable salt thereof.

[0512] In some embodiments, the compound of Formula I is a compound of Formula Villa: or a pharmaceutically acceptable salt thereof.

[0513] In some embodiments, the compound of Formula I is a compound of Formula Vlllb: 54057 -0028 WO 1 / SNV0021-W01 PATENT or a pharmaceutically acceptable salt thereof.

[0514] In some embodiments, the compound of Formula I is a compound of Formula VIIIc:

[0515] VIIIc or a pharmaceutically acceptable salt thereof.

[0516] In some embodiments, the compound provided herein is selected from:

[0517] 9-(difluoromethoxy)-13-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2,3-dihydro-lH- 10,16b-methanobenzo [f] benzo [4,5]imidazo [ 1 ,2-a]pyrrolo [2, 1 -c] [ 1 ,4]diazocin-5 ( 10H)-one ;

[0518] 13 -(2-( 1 -aminocyclobutyl)pyrimidin-5 -yl)-9-(difluoromethoxy)-2, 3 -dihydro- 1H- 10,16b-methanobenzo [f] benzo [4,5]imidazo [ 1 ,2-a]pyrrolo [2, 1 -c] [ 1 ,4]diazocin-5 ( 10H)-one ;

[0519] 2-(5 -( 1 -(difluoromethoxy) -5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0520] 9-(difluoromethoxy)- 13 -(4-(3 -methyl-3 -azabicyclo [3.1.0]hexan- 1 -yl)phenyl)-2,3- dihydro-lH-10,16b-methanobenzo[f]benzo[4,5]imidazo[l,2-a]pyrrolo[2,l-c][l,4]diazocin- 5(10H)-one;

[0521] 5 -( 1 -(difluoromethoxy) -5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)-3-fluoropyridin-2 -amine;

[0522] 1 -(difhroromethoxy)- 12-(2-(2 -hydroxypropan -2 -yl)pyrimidin-5 -yl)-5 , 15 -dihydro- 6H,8H-7,15-methanobenzo[g]benzo[4,5]imidazo[l,2-a][l,4]diazonin-6-one;

[0523] 1 -(difhroromethoxy)- 12-(2-(2 -hydroxypropan -2 -yl)pyrimidin-5 -yl)-5 , 15 -dihydro- 6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-7,8-dihydro-6H- 7,15-methanobenzo[g]benzo[4,5]imidazo[l,2-a][l,5]diazonin-5(15H)-one;

[0524] 1-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-6-methyl-7,8- dihydro-6H-7,15-methanobenzo[g]benzo[4,5]imidazo[l,2-a][l,5]diazonin-5(15H)-one;

[0525] 2-(5-(l-(difluoromethoxy)-4-(l-methyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0526] 2-(5-(l-(difluoromethoxy)-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0527] 2-(5-(l-(difluoromethoxy)-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0528] 2-(5-(l-(difluoromethoxy)-4-(l-(difluoromethyl)-lH-pyrazol-4-yl)-5,14-dihydro-7H-

[0529] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0530] 2-(5-(l-(difluoromethoxy)-4-(l-ethyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0531] 2-(5-(l-(difluoromethoxy)-4-(2-methyloxazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0532] 2-(5-(l-(difluoromethoxy)-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0533] 2-(5-(l-(difluoromethoxy)-2-methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-

[0534] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0535] 2-(5-(l-(difluoromethoxy)-2-methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0536] 2-(5-(l-(difluoromethoxy)-4-(methoxymethyl)-2-methyl-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0537] 2-(5-(l-(difluoromethoxy)-2-methyl-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0538] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0539] 2-(5-(l-(difluoromethoxy)-4-(hydroxymethyl)-2-methyl-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0540] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-pyrazol-4-yl)-5 , 14-dihydro-7H-

[0541] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0542] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-

[0543] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0544] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0545] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(methoxymethyl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0546] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyloxazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0547] 6-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-2- methylpyridazin-3 (2H) -one ;

[0548] 2-(5 -(4-(5 -amino- 1 -methyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro-5 ,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0549] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0550] 2-(5-(l-(difluoromethoxy)-4-(l-ethyl-lH-pyrazol-3-yl)-2-fluoro-5,14-dihydro-7H-

[0551] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0552] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0553] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0554] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- 1H- 1 ,2,4-triazol-3 -yl)-5 , 14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol;

[0555] 2-(5-( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -(pyridin-3-yhnethyl)- lH-pyrazol-4-yl)-5, 14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0556] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-imidazol-4-yl)-5 , 14-dihydro-7H-

[0557] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0558] 3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0559] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)tetrahydrofuran-3 -ol ;

[0560] 4-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0561] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)tetrahydro-2H-pyran-4-ol;

[0562] 5-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0563] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-5- methylimidazolidine-2, 4-dione; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0564] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0565] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propane- 1,2-diol;

[0566] 3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0567] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)-3-fluoropyridin-2-yl)-3- hydroxy- 1 -methylcyclobutane - 1 -carbonitrile ;

[0568] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0569] 6.14-methanobenzo[f]benzo[4,5]imidazo[ 1 ,2-a] [ 1 ,4]diazocin- 11 -yl)pyrimidin-2-yl)- 1 - methoxypropan-2-ol;

[0570] 3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0571] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- hydroxybutanenitrile ;

[0572] (l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0573] 6.14-methanobenzo [f] benzo [4,5] imidazo [ 1 ,2 -a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)cyclobutyl)methanol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0574] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)cyclobutan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2-yl)- 1 -( 1 - methyl- lH-pyrazol-4-yl)ethan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0575] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)cyclobutane- 1 -carboxamide; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0576] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)piperidin-

[0577] 4-ol;

[0578] (3-amino-3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)- 1 -methylcyclobutyl)methanol;

[0579] (3-amino-3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-

[0580] 5.14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)- 1 -methylcyclobutyl)methanol;

[0581] 3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0582] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)tetrahydrofuran-3 -amine ; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0583] 3 -amino-3 -(5 -( 1 -(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5 -yl)-5 ,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)- 1 -methylcyclobutan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0584] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- (hydroxymethyl) -3 -methylcyclobutan- 1 -ol ; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0585] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- (hydroxymethyl)cyclobutan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0586] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- methylcyclobutane - 1 , 3 -diol;

[0587] 1-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0588] 6.14-methanobenzo [f]benzo [4,5] imidazo [ 1 ,2-a] [ 1 ,4]diazocin- 11 -yl)pyrimidin-2- yl)cyclobutane - 1 , 3 -diol ;

[0589] 1 -( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-5 ,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)pyrrolidine-3- carbonitrile;

[0590] 2-(5 -( 1 -(difluoromethoxy)- 10-fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-

[0591] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0592] 2-(5-(l-(difluoromethoxy)-10-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0593] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0594] 2-(5-(l-(difluoromethoxy)-9-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0595] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0596] 2-(5 -( 1 -(difluoromethoxy)-9-fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-

[0597] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0598] 2-(5-(l-(difluoromethoxy)-2,9-difluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol;

[0599] 2-(5-(l-(difluoromethoxy)-2,9-difluoro-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol; 54057 -0028 WO 1 / SNV0021-W01 PATENT l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2-methyl-5,15- dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2,4-dimethyl-

[0600] 5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;

[0601] 1 -(difluoromethoxy)- 12-(2-(2 -hydroxypropan -2 -yl)pyrimidin-5 -yl)-2 -methyl -4-( 1 - methyl-lH-pyrazol-3-yl)-5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l- e] [ 1 ,3 ,6]triazonin-6-one;

[0602] 1-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2-methyl-4-(2- methyl-2H- 1 ,2,3 -triazol-4-yl)-5 , 15 -dihydro-6H,8H-7, 15- methanobenzo[h]benzo[4,5]imidazo[2, 1 -e] [ l,3,6]triazonin-6-one;

[0603] 1 -(difluoromethoxy)-4-fluoro- 12-(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl) -5 ,15- dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;

[0604] 2-cyclopropyl-l-(difluoromethoxy)-4-fluoro-12-(2-(2-hydroxypropan-2-yl)pyrimidin- 5 -yl) -5 , 15 -dihydro-6H, 8H-7, 15 -methanobenzo [h]benzo [4,5] imidazo[2, 1 -e] [ 1 ,3 ,6]triazonin-6- one;

[0605] 12-(2-(2 -aminopropan -2 -yl)pyrimidin-5-yl)-l-(difluoromethoxy)-4-fluoro-2 -methyl-

[0606] 5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2,5-dimethyl-

[0607] 5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;

[0608] 1 -(difluoromethoxy)- 12-(2-(3 -hydroxy oxetan-3 -yl)pyrimidin-5 -yl)-2, 5 -dimethyl -

[0609] 5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;

[0610] 12-(2-(2 -aminopropan -2 -yl)pyrimidin-5 -yl)- 1 -(difluoromethoxy)-2,5 -dimethyl-5 ,15- dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; l-(difluoromethoxy)-2-fluoro-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-4- methyl-5 , 15 -dihydro-6H, 8H-7, 15 -methanobenzo [h]benzo [4,5]imidazo [2, 1 -e] [ 1 ,3 ,6]triazonin- 6-one;

[0611] 1-(difluoromethoxy)-2-fluoro-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-4-(2- methyl-2H- 1 ,2,3 -triazol-4-yl)-5 , 15 -dihydro-6H,8H-7, 15- methanobenzo[h]benzo[4,5]imidazo[2, 1 -e] [ l,3,6]triazonin-6-one;

[0612] 2-(5 -( 1 -(difluoromethoxy)- 1 OH, 17H-9, 17 -methanobenzo [h]benzo [4,5]imidazo [2, 1 - e]imidazo[l,2-a][l,3,6]triazonin-14-yl)pyrimidin-2-yl)propan-2-ol;

[0613] 1 -((4-( 1 -(difluoromethoxy)-2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)- 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)methyl)cyclopropane- 1 -carbonitrile; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0614] 5 -(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-

[0615] 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)picolinonitrile;

[0616] 2-(5 -( 1 -(difluoromethoxy)-4-(6,7-dihydro-5H-pyrazolo [5 , 1 -b] [ 1 ,3] oxazin-3 -yl)-2- fluoro-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)propan-2-ol;

[0617] 5 -(3 -( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-

[0618] 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- 1 ,2,4-triazol- 1 -yl)picolinonitrile;

[0619] 5-(3-(l-(difluoromethoxy)-2-fluoro-l l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-

[0620] 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)picolinonitrile;

[0621] 2-(5-( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -(6-(hydroxymethyl)pyridin-3-yl)-lH- pyrazol-4-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin- 1 l-yl)pyrimidin-2-yl)propan-2-ol;

[0622] 6-(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-

[0623] 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)nicotinonitrile;

[0624] N-cyclopropyl-5-(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- IH-pyrazol- 1 -yl)pyrimidine-2 -carboxamide;

[0625] N-cyclopropyl-5-(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- IH-pyrazol- 1 -yl)picolinamide;

[0626] N-( 1 -cyanocyclopropyl)-5-(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2- hydroxypropan-2-yl)pyrimidin-5-yl)-5, 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH-pyrazol-l-yl)picolinamide;

[0627] 6-(3 -( 1 -(difluoromethoxy)-2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-

[0628] 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)nicotinonitrile;

[0629] 2-(5-(4-(2-(cyclopropylmethyl)-2H-tetrazol-5-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0630] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(4,5,6,7-tetrahydropyrazolo[l,5-a]pyrimidin-2- yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)propan-2-ol; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0631] 5-(5-amino-3-(l-(difluoromethoxy)-2-fluoro-l l-(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- IH-pyrazol- 1 -yl)-N-cyclopropylpicolinamide;

[0632] 2-(5 -(4-(5 -((cyclopropylmethyl)amino)- 1 -methyl- lH-pyrazol-3 -yl)- 1 - (difluoromethoxy)-2-fluoro-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2- a] [ 1 ,4]diazocin- 11 -yl)pyrimidin-2-yl)propan-2-ol;

[0633] 2-(5-(4-([l,2,4]triazolo[l,5-a]pyrazin-2-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0634] 2-(5-(4-([l,2,4]triazolo[l,5-a]pyrimidin-2-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0635] 2-(5-(4-(5-amino-l-methyl-lH-l,2,4-triazol-3-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0636] N-cyclopropyl-5 -(3 -( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- 1H- 1 ,2,4-triazol- 1 -yl)picolinamide;

[0637] 2-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-6,7-dihydro- [ 1 ,2,4]triazolo [1,5 -a]pyrimidin-5 (4H)-one;

[0638] 2-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-6,7- dihydropyrazolo [ 1 ,5 -a]pyrimidin-5 (4H)-one ;

[0639] 2-(5 -(4-(5 -amino- 1 -cyclopropyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro-

[0640] 5.14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)propan-2-ol;

[0641] 1 -((5 -( 1 -(difluoromethoxy)-2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-

[0642] 5.14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-2H- tetrazol-2-yl)methyl)cyclopropane- 1 -carbonitrile; and

[0643] 2-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-5-methyl-6,7- dihydropyrazolo [ 1 ,5 -a]pyrazin-4(5H)-one ; or a pharmaceutically acceptable salt thereof.

[0644] In some embodiments, the compound provided herein is selected from: 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0645] (10R)-9-(difluoromethoxy)-13-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2,3- dihydro-lH-10,16b-methanobenzo[f]benzo[4,5]imidazo[l,2-a]pyrrolo[2,l-c][l,4]diazocin- 5(10H)-one;

[0646] ( 1 OR)- 13 -(2-( 1 -aminocyclobutyl)pyrimidin-5 -yl)-9-(difluoromethoxy)-2,3 -dihydro- lH-10,16b-methanobenzo[f]benzo[4,5]imidazo[l,2-a]pyrrolo[2,l-c][l,4]diazocin-5( 10H)- one;

[0647] 2-(5 -( 1 -(difluoromethoxy) -5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0648] ( 10R)-9-(difluoromethoxy)- 13 -(4-(( 1 R,5 S)-3 -methyl-3 -azabicyclo [3.1.0]hexan- 1 - yl)phenyl)-2,3 -dihydro- 1H- 10,16b-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a]pyrrolo [2, 1 - c] [ 1 ,4]diazocin-5( 10H)-one;

[0649] 5 -( 1 -(difluoromethoxy) -5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)-3-fluoropyridin-2 -amine; l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,15-dihydro- 6H,8H-7,15-methanobenzo[g]benzo[4,5]imidazo[l,2-a][l,4]diazonin-6-one;

[0650] 1-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,15-dihydro- 6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;

[0651] (7R, 15R)- 1 -(difluoromethoxy)- 12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-7, 8- dihydro-6H-7,15-methanobenzo[g]benzo[4,5]imidazo[l,2-a][l,5]diazonin-5(15H)-one;

[0652] (7R, 15R)- 1 -(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-6- methyl-7,8-dihydro-6H-7,15-methanobenzo[g]benzo[4,5]imidazo[l,2-a][l,5]diazonin- 5(15H)-one;

[0653] 2-(5-(l-(difluoromethoxy)-4-(l-methyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0654] 2-(5-(l-(difluoromethoxy)-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0655] 2-(5-(l-(difluoromethoxy)-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0656] 2-(5-(l-(difluoromethoxy)-4-(l-(difluoromethyl)-lH-pyrazol-4-yl)-5,14-dihydro-7H- 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0657] 2-(5-(l-(difluoromethoxy)-4-(l-ethyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0658] 2-(5-(l-(difluoromethoxy)-4-(2-methyloxazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0659] 2-(5-(l-(difluoromethoxy)-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0660] 2-(5-(l-(difluoromethoxy)-2-methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-

[0661] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0662] 2-(5-(l-(difluoromethoxy)-2-methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0663] 2-(5-(l-(difluoromethoxy)-4-(methoxymethyl)-2-methyl-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0664] 2-(5-(l-(difluoromethoxy)-2-methyl-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0665] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0666] 2-(5-(l-(difluoromethoxy)-4-(hydroxymethyl)-2-methyl-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0667] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-pyrazol-4-yl)-5 , 14-dihydro-7H-

[0668] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0669] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-

[0670] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0671] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol;

[0672] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(methoxymethyl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0673] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyloxazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;

[0674] 6-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-2- methylpyridazin-3 (2H) -one ;

[0675] 2-(5 -(4-(5 -amino- 1 -methyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro-5 ,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0676] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0677] 2-(5-(l-(difluoromethoxy)-4-(l-ethyl-lH-pyrazol-3-yl)-2-fluoro-5,14-dihydro-7H-

[0678] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0679] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0680] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0681] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- 1H- 1 ,2,4-triazol-3 -yl)-5 , 14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol;

[0682] 2-(5-( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -(pyridin-3-ylmethyl)- lH-pyrazol-4-yl)-5, 14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0683] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-imidazol-4-yl)-5 , 14-dihydro-7H-

[0684] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0685] 3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0686] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)tetrahydrofuran-3 -ol ;

[0687] 4-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0688] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)tetrahydro-2H-pyran-4-ol;

[0689] 5-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0690] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-5- methylimidazolidine-2, 4-dione;

[0691] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0692] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propane- 1,2-diol;

[0693] 3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0694] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)-3-fluoropyridin-2-yl)-3- hydroxy- 1 -methylcyclobutane - 1 -carbonitrile ;

[0695] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0696] 6.14-methanobenzo[f]benzo[4,5]imidazo[ 1 ,2-a] [ 1 ,4]diazocin- 11 -yl)pyrimidin-2-yl)- 1 - methoxypropan-2-ol;

[0697] 3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0698] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- hydroxybutanenitrile ; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0699] (l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0700] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)cyclobutyl)methanol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0701] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)cyclobutan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2-yl)- 1 -( 1 - methyl- lH-pyrazol-4-yl)ethan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0702] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)cyclobutane- 1 -carboxamide; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0703] 6.14-methanobenzo [f]benzo [4,5] imidazo [ 1 ,2-a] [ 1 ,4]diazocin- 11 -yl)pyrimidin-2-yl)piperidin- 4-ol;

[0704] (3-amino-3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)- 1 -methylcyclobutyl)methanol;

[0705] (3-amino-3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-

[0706] 5.14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)- 1 -methylcyclobutyl)methanol;

[0707] 3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0708] 6.14-methanobenzo [f] benzo [4,5] imidazo [ 1 ,2 -a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)tetrahydrofuran-3 -amine ;

[0709] 3 -amino-3 -(5 -( 1 -(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5 -yl)-5 ,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)- 1 -methylcyclobutan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0710] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- (hydroxymethyl) -3 -methylcyclobutan- 1 -ol ; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0711] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- (hydroxymethyl)cyclobutan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0712] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- methylcyclobutane - 1 , 3 -diol; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0713] 1-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0714] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)cyclobutane - 1 , 3 -diol ;

[0715] 1 -( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-5 ,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)pyrrolidine-3- carbonitrile;

[0716] 2-(5 -( 1 -(difluoromethoxy)- 10-fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-

[0717] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0718] 2-(5-(l-(difluoromethoxy)-10-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0719] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0720] 2-(5-(l-(difluoromethoxy)-9-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0721] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0722] 2-(5 -( 1 -(difluoromethoxy)-9-fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-

[0723] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0724] 2-(5-(l-(difluoromethoxy)-2,9-difluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro- 7H-6, 14-methanobenzo[f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol;

[0725] 2-(5-(l-(difluoromethoxy)-2,9-difluoro-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol; l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2-methyl-5,15- dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2,4-dimethyl-

[0726] 5.15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;

[0727] 1 -(difluoromethoxy)- 12-(2-(2 -hydroxypropan -2 -yl)pyrimidin-5 -yl)-2 -methyl -4-( 1 - methyl-lH-pyrazol-3-yl)-5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l- e] [ 1 ,3 ,6]triazonin-6-one; l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2-methyl-4-(2- methyl -2H- 1 ,2,3 -triazol-4-yl)-5 , 15 -dihydro-6H,8H-7, 15- methanobenzo[h]benzo[4,5]imidazo[2, 1 -e] [ l,3,6]triazonin-6-one;

[0728] 1 -(difluoromethoxy)-4-fluoro- 12-(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl) -5 ,15- dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0729] 2-cyclopropyl-l-(difluoromethoxy)-4-fluoro-12-(2-(2-hydroxypropan-2-yl)pyrimidin-

[0730] 5 -yl) -5 , 15 -dihydro-6H, 8H-7, 15 -methanobenzo [h]benzo [4,5] imidazo[2, 1 -e] [ 1 ,3 ,6]triazonin-6- one;

[0731] 12-(2-(2 -aminopropan -2 -yl)pyrimidin-5-yl)-l-(difluoromethoxy)-4-fluoro-2 -methyl-

[0732] 5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2,5-dimethyl-

[0733] 5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;

[0734] 1 -(difluoromethoxy)- 12-(2-(3 -hydroxy oxetan-3 -yl)pyrimidin-5 -yl)-2, 5 -dimethyl -

[0735] 5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;

[0736] 12-(2-(2 -aminopropan -2 -yl)pyrimidin-5 -yl)- 1 -(difluoromethoxy)-2,5 -dimethyl-5 ,15- dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; l-(difluoromethoxy)-2-fluoro-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-4- methyl-5 , 15 -dihydro-6H, 8H-7, 15 -methanobenzo [h]benzo [4,5]imidazo [2, 1 -e] [ 1 ,3 ,6]triazonin- 6-one;

[0737] 1-(difluoromethoxy)-2-fluoro-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-4-(2- methyl-2H- 1 ,2,3 -triazol-4-yl)-5 , 15 -dihydro-6H,8H-7, 15- methanobenzo[h]benzo[4,5]imidazo[2, 1 -e] [ l,3,6]triazonin-6-one;

[0738] 2-(5 -( 1 -(difluoromethoxy)- 1 OH, 17H-9, 17 -methanobenzo [h]benzo [4,5]imidazo [2, 1 - e]imidazo[l,2-a][l,3,6]triazonin-14-yl)pyrimidin-2-yl)propan-2-ol;

[0739] 1 -((4-( 1 -(difluoromethoxy)-2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-

[0740] 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)methyl)cyclopropane- 1 -carbonitrile;

[0741] 5 -(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-

[0742] 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)picolinonitrile;

[0743] 2-(5 -( 1 -(difluoromethoxy)-4-(6,7-dihydro-5H-pyrazolo [5 , 1 -b] [ 1 ,3] oxazin-3 -yl)-2- fluoro-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)propan-2-ol;

[0744] 5-(3-(l-(difluoromethoxy)-2-fluoro-l l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-

[0745] 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- 1 ,2,4-triazol- 1 -yl)picolinonitrile;

[0746] 5-(3-(l-(difluoromethoxy)-2-fluoro-l l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-

[0747] 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)picolinonitrile; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0748] 2-(5-( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -(6-(hydroxymethyl)pyridin-3-yl)-lH- pyrazol-4-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin- 1 l-yl)pyrimidin-2-yl)propan-2-ol;

[0749] 6-(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)- 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)nicotinonitrile;

[0750] N-cyclopropyl-5-(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- IH-pyrazol- 1 -yl)pyrimidine-2 -carboxamide;

[0751] N-cyclopropyl-5-(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- IH-pyrazol- 1 -yl)picolinamide;

[0752] N-( 1 -cyanocyclopropyl)-5-(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2- hydroxypropan-2-yl)pyrimidin-5-yl)-5, 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH-pyrazol-l-yl)picolinamide;

[0753] 6-(3 -( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)- 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)nicotinonitrile;

[0754] 2-(5-(4-(2-(cyclopropyhnethyl)-2H-tetrazol-5-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0755] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(4,5,6,7-tetrahydropyrazolo[l,5-a]pyrimidin-2- yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)propan-2-ol;

[0756] 5 -(5 -amino-3 -( 1 -(difluoromethoxy)-2-fluoro- 11 -(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- IH-pyrazol- 1 -yl)-N-cyclopropylpicolinamide;

[0757] 2-(5 -(4-(5 -((cyclopropylmethyl)amino)- 1 -methyl- lH-pyrazol-3 -yl)- 1 - (difluoromethoxy)-2-fluoro-5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo[4,5] imidazo [1,2- a] [ 1 ,4]diazocin- 11 -yl)pyrimidin-2-yl)propan-2-ol;

[0758] 2-(5-(4-([l,2,4]triazolo[l,5-a]pyrazin-2-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0759] 2-(5-(4-([l,2,4]triazolo[l,5-a]pyrimidin-2-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0760] 2-(5-(4-(5-amino-l-methyl-lH-l,2,4-triazol-3-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0761] N-cyclopropyl-5 -(3 -( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- 1H- 1 ,2,4-triazol- 1 -yl)picolinamide;

[0762] 2-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-6,7-dihydro- [ 1 ,2,4]triazolo [1,5 -a]pyrimidin-5 (4H)-one;

[0763] 2-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-6,7- dihydropyrazolo [ 1 ,5 -a]pyrimidin-5 (4H)-one ;

[0764] 2-(5 -(4-(5 -amino- 1 -cyclopropyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro-

[0765] 5.14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)propan-2-ol;

[0766] 1 -((5 -( 1 -(difluoromethoxy)-2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-

[0767] 5.14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-2H- tetrazol-2-yl)methyl)cyclopropane- 1 -carbonitrile; and

[0768] 2-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-5-methyl-6,7- dihydropyrazolo [ 1 ,5 -a]pyrazin-4(5H)-one ; or a pharmaceutically acceptable salt thereof.

[0769] In some embodiments, the compound provided herein is selected from:

[0770] 2-(5-(l-(difluoromethoxy)-2-methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-

[0771] 6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0772] 2-(5-(l-(difluoromethoxy)-2-methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0773] 2-(5-(l-(difluoromethoxy)-2-methyl-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-

[0774] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0775] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-pyrazol-4-yl)-5 , 14-dihydro-7H-

[0776] 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0777] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl) -5 , 14-dihydro-7H- 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;

[0778] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol;

[0779] 2-(5 -(4-(5 -amino- 1 -methyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro-5 ,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0780] 2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H- 6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol; and

[0781] 2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- 1H- 1 ,2,4-triazol-3 -yl)-5 , 14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol; or a pharmaceutically acceptable salt thereof.

[0782] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0783] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0784] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0785] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0786] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- methyl-4-(2-methyl-2H-tetrazol-5-yl)-5, 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0787] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- methyl-4-(2-methyl-2H-tetrazol-5-yl)-5, 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0788] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- fluoro-4-(l-methyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0789] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- fluoro-4-(l-methyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0790] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl)-5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0791] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl)-5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0792] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0793] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0794] In some embodiments, the compound provided herein is 2-(5-(4-(5-amino-l-methyl- lH-pyrazol-3-yl)-l-(difhroromethoxy)-2-fluoro-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0795] In some embodiments, the compound provided herein is 2-(5-(4-(5-amino-l-methyl- lH-pyrazol-3-yl)-l-(difhroromethoxy)-2-fluoro-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0796] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5, 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0797] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5, 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0798] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- fluoro-4-( 1 -methyl- 1H- 1 ,2,4-triazol-3 -yl) -5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0799] In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- fluoro-4-( 1 -methyl- 1H- 1 ,2,4-triazol-3 -yl) -5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[I,2-a][I,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0800] In some embodiments, the compound provided herein is 3-(5-(l-(difluoromethoxy)-2- fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5, 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)tetrahydrofuran-3-ol, or a pharmaceutically acceptable salt thereof.

[0801] In some embodiments, the compound provided herein is 3-(5-(l-(difluoromethoxy)-2- fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5, 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)tetrahydrofuran-3 -ol .

[0802] In some embodiments, the compound provided herein is selected from:

[0803] 2-(5 -(( 14R)- 1 -(difluoromethoxy)-2 -methyl -4-( 1 -methyl- lH-pyrazol-3 -yl) -5 ,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[I,2-a] [1, 4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0804] 2-(5-((14S)-I-(difhroromethoxy)-2-methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[I,2-a] [1, 4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0805] 2-(5-((14R)-l-(difhioromethoxy)-2-methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[I,2-a] [1, 4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0806] 2-(5-((14S)-I-(difhioromethoxy)-2-methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[I,2-a] [1, 4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0807] 2-(5 -(( 14R)- 1 -(difhroromethoxy)-2 -methyl -4-(2-methyl -2H-tetrazol-5 -yl)-5 , 14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[I,2-a] [1, 4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0808] 2-(5-((14S)-l-(difluoromethoxy)-2-methyl-4-(2-methyl-2H-tetrazol-5-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0809] 2-(5-((14R)-l-(difluoromethoxy)-2-fluoro-4-(l-methyl-lH-pyrazol-4-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0810] 2-(5-((14S)-l-(difluoromethoxy)-2-fluoro-4-(l-methyl-lH-pyrazol-4-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0811] 2-(5 -(( 14R)- 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl) -5 ,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0812] 2-(5-((14S)-l-(difluoromethoxy)-2-fluoro-4-(l-methyl-lH-pyrazol-3-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0813] 2-(5-((14R)-l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0814] 2-(5-((14S)-l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0815] 2-(5 -(( 14R)-4-(5 -amino- 1 -methyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro- 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)propan-2-ol;

[0816] 2-(5-(( 14S)-4-(5-amino- 1 -methyl- lH-pyrazol-3-yl)- 1 -(difluoromethoxy)-2 -fluoro- 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)propan-2-ol;

[0817] 2-(5-((14R)-l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0818] 2-(5-((14S)-l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0819] 2-(5-((14R)-l-(difluoromethoxy)-2-fluoro-4-(l-methyl-lH-l,2,4-triazol-3-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol; 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0820] 2-(5-((14S)-l-(difluoromethoxy)-2-fluoro-4-(l-methyl-lH-l,2,4-triazol-3-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;

[0821] (3R)-3-(5-((14R)-l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)tetrahydrofuran-3 -ol ;

[0822] (3S)-3-(5-((14R)-l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)tetrahydrofuran-3 -ol ;

[0823] (3R)-3-(5-((14S)-l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)tetrahydrofuran-3-ol; and

[0824] (3S)-3-(5-((14S)-l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)tetrahydrofuran-3 -ol ; or a pharmaceutically acceptable salt thereof.

[0825] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difluoromethoxy)-2-methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0826] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difluoromethoxy)-2-methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0827] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difluoromethoxy)-2-methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0828] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difluoromethoxy)-2-methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0829] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difhioromethoxy)-2-methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0830] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difluoromethoxy)-2-methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0831] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difluoromethoxy)-2-methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0832] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difluoromethoxy)-2-methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0833] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difluoromethoxy)-2-methyl-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0834] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difluoromethoxy)-2-methyl-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0835] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difluoromethoxy)-2-methyl-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0836] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difluoromethoxy)-2-methyl-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0837] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difhioromethoxy)-2-fluoro-4-(l-methyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0838] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difhioromethoxy)-2-fluoro-4-(l-methyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0839] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difhioromethoxy)-2-fluoro-4-(l-methyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0840] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difluoromethoxy)-2-fluoro-4-(l-methyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0841] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difluoromethoxy)-2-fluoro-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0842] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difluoromethoxy)-2-fluoro-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0843] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difluoromethoxy)-2-fluoro-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0844] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difhioromethoxy)-2-fluoro-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0845] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difhioromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0846] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difhioromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0847] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difhioromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0848] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difhioromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0849] In some embodiments, the compound provided herein is 2-(5-((14R)-4-(5-amino-l- methyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro-5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0850] In some embodiments, the compound provided herein is 2-(5 -((14R)-4-(5 -amino- 1- methyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro-5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0851] In some embodiments, the compound provided herein is 2-(5-((14S)-4-(5-amino-l- methyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro-5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0852] In some embodiments, the compound provided herein is 2-(5-((14S)-4-(5-amino-l- methyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro-5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[I,2-a][I,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0853] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0854] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difhioromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0855] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difhioromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0856] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difhioromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0857] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difhioromethoxy)-2-fluoro-4-(l-methyl-lH-l,2,4-triazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

[0858] In some embodiments, the compound provided herein is 2-(5-((14R)-l- (difhioromethoxy)-2-fluoro-4-(l-methyl-lH-l,2,4-triazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0859] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difhioromethoxy)-2-fluoro-4-(l-methyl-lH-l,2,4-triazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0860] In some embodiments, the compound provided herein is 2-(5-((14S)-l- (difluoromethoxy)-2-fluoro-4-(l-methyl-lH-l,2,4-triazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol.

[0861] It is further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination.

[0862] At various places in the present specification, divalent linking substituents are described. It is specifically intended that each divalent linking substituent include both the forward and backward forms of the linking substituent. For example, -NR(CR’R”)n- includes both -NR(CR’R”)n- and -(CR’R”)nNR-. Where the structure clearly requires a linking group, the Markush variables listed for that group are understood to be linking groups.

[0863] The term “n-membered” where n is an integer typically describes the number of ringforming atoms in a moiety where the number of ring-forming atoms is n. For example, piperidinyl is an example of a 6-membered heterocycloalkyl ring, pyrazolyl is an example of a 5-membered heteroaryl ring, pyridyl is an example of a 6-membered heteroaryl ring, and 1,2,3,4-tetrahydro-naphthalene is an example of a 10-membered cycloalkyl group.

[0864] As used herein, the phrase “optionally substituted” means unsubstituted or substituted. The substituents are independently selected, and substitution may be at any chemically accessible position. As used herein, the term “substituted” means that a hydrogen atom is removed and replaced by a substituent. A single divalent substituent, e.g., oxo, can replace two hydrogen atoms. It is to be understood that substitution at a given atom is limited by valency.

[0865] As used herein, the phrase “each ‘variable’ is independently selected from” means substantially the same as wherein “at each occurrence ‘variable’ is selected from.”

[0866] Throughout the definitions, the terms “Cn-m” and “Cm-n” indicates a range which includes the endpoints, wherein n and m are integers and indicate the number of carbons. Examples include C1-3, C1-4, C1-6, and the like.

[0867] As used herein, the term “Cn-malkyl”, employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chain or branched, having n to m carbons. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl (Me), ethyl (Et), n-propyl (n-Pr), isopropyl (iPr), n-butyl, tert-butyl, isobutyl, sec-butyl; higher homologs such as 2-methyl-l -butyl, n-pentyl, 3-pentyl, n-hexyl, 1,2,2- trimethylpropyl, and the like. The term “Cn-malkyl” is understood to include deuterated analogs of saturated hydrocarbon groups as defined herein, including but not limited to, 54057 -0028 WO 1 / SNV0021-W01 PATENT groups such as trideuteromethyl (CDs), pentadeuteroethyl (CD2CD3), and the like. In some embodiments, the alkyl group contains from 1 to 6 carbon atoms, from 1 to 4 carbon atoms, from 1 to 3 carbon atoms, from 2 to 6 carbon atoms, from 2 to 4 carbon atoms, from 2 to 3 carbon atoms, or 1 to 2 carbon atoms.

[0868] As used herein, “Cn-malkenyl” refers to an alkyl group having one or more double carbon-carbon bonds and having n to m carbons. Example alkenyl groups include, but are not limited to, ethenyl, n-propenyl, isopropenyl, n-butenyl, sec-butenyl, and the like. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. The term “Corn alkenyl” is understood to include deuterated analogs of alkenyl groups as defined herein, including but not limited to, groups such as trideuteroethenyl (-CD=CD2), tetradeuteropropenyl, (-CD=CD-CD2), and the like.

[0869] As used herein, “Cn-malkynyl” refers to an alkyl group having one or more triple carbon-carbon bonds and having n to m carbons. Example alkynyl groups include, but are not limited to, ethynyl, propyn-l-yl, propyn-2-yl, and the like. In some embodiments, the alkynyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. The term “Cn-malkynyl” is understood to include deuterated analogs of alkynyl groups as defined herein, including but not limited to, groups such as deuteroethynyl (-C=CD), trideuteropropyn-l-yl, (-C=CCDs), and the like.

[0870] As used herein, the term “Cn-malkoxy”, employed alone or in combination with other terms, refers to a group of formula -O-alkyl, wherein the alkyl group has n to m carbons. Example alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy (e.g., n- propoxy and isopropoxy), butoxy (e.g., n-butoxy and tert-butoxy), and the like. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. The term “Cn-malkoxy” is understood to include deuterated analogs of the alkyl moiety of the alkoxy groups as defined herein, including but not limited to, groups such as trideuteromethoxy (-OCD3), pentadeuteroethoxy (-OCD2CD3), and the like.

[0871] As used herein, “Cn-mhaloalkoxy”, employed alone or in combination with other terms, refers to a group of formula -O-(haloalkyl), wherein the haloalkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. An example haloalkoxy group is -OCF3. In some embodiments, the haloalkoxy group is a fluoroalkoxy group. The term “Cn-mhaloalkoxy” is understood to include deuterated analogs of the haloalkoxy groups as defined herein.

[0872] As used herein, the term “carbonyl”, employed alone or in combination with other terms, refers to a -C(O)- group.

[0873] As used herein, the term “Cn-malkylcarbonyl” refers to a group of formula -C(O)- alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl 54057 -0028 WO 1 / SNV0021-W01 PATENT group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. The term “Cn-malkylcarbonyl” is understood to include deuterated analogs of the alkylcarbonyl groups as defined herein.

[0874] As used herein, the term “Cn-malkylsulfonyl” refers to a group of formula -S(O)2- alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. The term “Cn-malkylsulfonyl” is understood to include deuterated analogs of the alkylsulfonyl groups as defined herein.

[0875] As used herein, the term “carboxy” refers to a group of formula -C(O)OH.

[0876] As used herein, the term “amino” refers to a group of formula -NH2.

[0877] As used herein, the term “Cn-malkylamino”, employed alone or in combination with other terms, refers to a group of formula -NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, alkyl group has 1 to 6 or 1 to 4 carbon atoms. Example alkylamino groups include methylamino, ethylamino, propylamino (e.g., n-propylamino and isopropylamino), and the like. The term “Cn-malkylamino” is understood to include deuterated analogs of the alkylamino groups as defined herein.

[0878] As used herein, the term “di(Cn-malkyl)amino” refers to a group of formula - N(alkyl)2, wherein the two alkyl groups each has, independently, n to m carbon atoms. In some embodiments, each alkyl group independently has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. The term “di(Cn-malkyl)amino” is understood to include deuterated analogs of the di(Cn-malkyl)amino groups as defined herein.

[0879] As used herein, the term “Cn-malkoxycarbonyl”, employed alone or in combination with other terms, refers to a group of formula -C(O)O-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. The term “Cn-malkoxycarbonyl” is understood to include deuterated analogs of the alkoxycarbonyl groups as defined herein.

[0880] As used herein, the term “Cn-malkylcarbonyl”, employed alone or in combination with other terms, refers to a group of formula -C(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. The term “Cn-malkylcarbonyl” is understood to include deuterated analogs of the alkylcarbonyl groups as defined herein.

[0881] As used herein, the term “Cn-malkylcarbonylamino”, employed alone or in combination with other terms, refers to a group of formula -NHC(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. The term “Cn-malkylcarbonylamino” is understood to include deuterated analogs of the alkylcarbonylamino groups as defined herein.

[0882] As used herein, the term “carbamyl”, employed alone or in combination with other terms, refers to a group of formula -C(O)-NH2. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0883] As used herein, the term “Cn-malkylcarbamyl”, employed alone or in combination with other terms, refers to a group of formula -C(O)-NH(alkyl), wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. The term “Cn-malkylcarbamyl” is understood to include deuterated analogs of the alkylcarbamyl groups as defined herein.

[0884] As used herein, the term “di-Cn-malkylcarbamyl”, employed alone or in combination with other terms, refers to a group of formula -C(O)-N(alkyl)2, wherein each alkyl group independently has n to m carbon atoms. In some embodiments, the alkyl group independently has 1 to 6 or 1 to 4 carbon atoms. The term “di-Cn-malkylcarbamyl” is understood to include deuterated analogs of the dialkylcarbamyl groups as defined herein.

[0885] As used herein, the term “thio” refers to a group of formula -SH.

[0886] As used herein, the term “Cn-malkylthio”, employed alone or in combination with other terms, refers to a group of formula -S-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. The term “Corn alkylthio” is understood to include deuterated analogs of the alkylthio groups as defined herein.

[0887] As used herein, the term “Cn-malkylsulfinyl”, employed alone or in combination with other terms, refers to a group of formula -S(O)-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. The term “Cn-malkylsulfinyl” is understood to include deuterated analogs of the alkylsulfinyl groups as defined herein.

[0888] As used herein, the term “Cn-malkylsulfonyl”, employed alone or in combination with other terms, refers to a group of formula -S(O)2-alkyl, wherein the alkyl group has n to m carbon atoms. In some embodiments, the alkyl group has 1 to 6 or 1 to 4 carbon atoms. The term “Cn-malkylsulfonyl” is understood to include deuterated analogs of the alkylsulfonyl groups as defined herein.

[0889] As used herein, “halosulfanyl” refers to a sulfur group having one or more halogen substituents. Example halosulfanyl groups include pentahalosulfanyl groups such as SF5.

[0890] As used herein, the term “HO-C1-4 alkyl” refers to a group of formula -Ci-4alkylene- OH. The term “HO-C1-4 alkyl” is understood to include deuterated analogs of the HO-C1-4 alkyl groups as defined herein.

[0891] As used herein, the term “Ci-4alkoxy-Ci-4alkyl” refers to a group of formula -C1-4 alkylene-O-(Ci-4 alkyl). The term “Ci-4alkoxy-Ci-4 alkyl” is understood to include deuterated analogs of the Ci-4alkoxy-Ci-4 alkyl groups as defined herein.

[0892] As used herein, the term “aryl,” employed alone or in combination with other terms, refers to an aromatic hydrocarbon group, which may be monocyclic or polycyclic (e.g., 54057 -0028 WO 1 / SNV0021-W01 PATENT having 2, 3 or 4 fused rings). The term “Cn-maryl” refers to an aryl group having from n to m ring carbon atoms. Aryl groups include, e.g., phenyl, naphthyl, anthracenyl, phenanthrenyl, and the like. In some embodiments, aryl groups have from 5 to 10 carbon atoms. In some embodiments, the aryl group is phenyl or naphthyl. In some embodiments, the aryl is phenyl. The term “aryl” is understood to include deuterated analogs of the aryl groups as defined herein, including but not limited to, groups such as pentadeuterophenyl (z.e., perdeuterophenyl, phenyl - j), perdeuteronaphthyl, and the like.

[0893] As used herein, “halo” refers to F, Cl, Br, or I. In some embodiments, a halo is F, Cl, or Br. In some embodiments, a halo is F or Cl. In some embodiments, a halo is F. In some embodiments, a halo is Cl.

[0894] As used herein, “Cn-mhaloalkoxy” refers to a group of formula -O-haloalkyl having n to m carbon atoms. Example haloalkoxy groups include OCFs and OCHF2. In some embodiments, the haloalkoxy group is fluorinated only. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. The term “Cn-mhaloalkoxy” is understood to include deuterated analogs of the haloalkyl moiety of the haloalkoxy groups as defined herein, including but not limited to, groups such as deuterodifluoromethoxy (-OCDF2), dideuterofluoromethoxy (-OCD2F), and the like.

[0895] As used herein, the term “Cn-mhaloalkyl”, employed alone or in combination with other terms, refers to an alkyl group having from one halogen atom to 2s+l halogen atoms which may be the same or different, where “s” is the number of carbon atoms in the alkyl group, wherein the alkyl group has n to m carbon atoms. In some embodiments, the haloalkyl group is fluorinated only. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms. Example haloalkyl groups include CF3, C2F5, CHF2, CH2F, CCI3, CHCE, C2CI5 and the like. The term “Cn-mhaloalkyl” is understood to include deuterated analogs of the haloalkyl groups as defined herein, including but not limited to, groups such as deuterodifluoromethyl (-CDF2), dideuterofluoromethyl (-CD2F), and the like.

[0896] As used herein, “hydroxyl” or “hydroxy” refer to a group of formula -OH.

[0897] As used herein, “cycloalkyl” refers to non-aromatic cyclic hydrocarbons including cyclized alkyl and alkenyl groups. Cycloalkyl groups can include mono- or polycyclic (e.g., having 2 fused rings) groups, spirocycles, and bridged rings (e.g., a bridged bicycloalkyl group). Ring -forming carbon atoms of a cycloalkyl group can be optionally substituted by oxo or sulfido (e.g., C(O) or C(S)). Also included in the definition of cycloalkyl are moieties that have one or more aromatic rings fused (z.e., having a bond in common with) to the cycloalkyl ring, for example, benzo or thienyl derivatives of cyclopentane, cyclohexane, and the like. A cycloalkyl group containing a fused aromatic ring can be attached through any ring -forming atom including a ring -forming atom of the fused aromatic ring. Cycloalkyl 54057 -0028 WO 1 / SNV0021-W01 PATENT groups can have 3, 4, 5, 6, 7, 8, 9, or 10 ring-forming carbons (z.e., C3-10). In some embodiments, the cycloalkyl is a C3- 10 monocyclic or bicyclic cycloalkyl. In some embodiments, the cycloalkyl is a C3-7 monocyclic cycloalkyl. In some embodiments, the cycloalkyl is a C4-7 monocyclic cycloalkyl. In some embodiments, the cycloalkyl is a C4-10 spirocycle or bridged cycloalkyl (e.g., a bridged bicycloalkyl group). Example cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptatrienyl, norbomyl, norpinyl, norcamyl, cubane, adamantane, bicyclo [1. 1.1 ]pentyl, bicyclo [2. l.l]hexyl, bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl, bicyclo[2.2.2]octanyl, spiro[3.3]heptanyl, and the like. In some embodiments, cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. The term “cycloalkyl” is understood to include deuterated analogs of the cycloalkyl groups as defined herein, including but not limited to, groups such as perdeuterocyclopropyl, perdeuterocyclobutyl, perdeuterocyclopentyl, perdeuterocyclohexyl, and the like.

[0898] As used herein, “heteroaryl” refers to a monocyclic or polycyclic (e.g., having 2 fused rings) aromatic heterocycle having at least one heteroatom ring member selected from N, O, S and B. In some embodiments, the heteroaryl ring has 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, S and B. In some embodiments, any ring -forming N in a heteroaryl moiety can be an N-oxide. In some embodiments, the heteroaryl is a 5-10 membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, S, and B. In some embodiments, the heteroaryl is a 5-, 7-, 8-, 9-, or 10-membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, S, and B. In some embodiments, the heteroaryl is a 5-10 membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, and S. In some embodiments, the heteroaryl is a 5-, 7-, 8-, 9-, or 10-membered monocyclic or bicyclic heteroaryl having 1, 2, 3, or 4 heteroatom ring members independently selected from N, O, and S. In some embodiments, the heteroaryl is a 5-6 membered monocyclic heteroaryl having 1 or 2 heteroatom ring members independently selected from N, O, S, and B. In some embodiments, the heteroaryl is a 5 membered monocyclic heteroaryl having 1 or 2 heteroatom ring members independently selected from N, O, S, and B. In some embodiments, the heteroaryl is a 5 membered monocyclic heteroaryl having 1 or 2 heteroatom ring members independently selected from N, O, and S. In some embodiments, the heteroaryl group contains 5 to 10, 5 to 7, 3 to 7, or 5 to 6 ring-forming atoms. In some embodiments, the heteroaryl group has 1 to 4 ring-forming heteroatoms, 1 to 3 ring-forming heteroatoms, 1 to 2 ring-forming heteroatoms or 1 ringforming heteroatom. When the heteroaryl group contains more than one heteroatom ring member, the heteroatoms may be the same or different. Example heteroaryl groups include, 54057 -0028 WO 1 / SNV0021-W01 PATENT but are not limited to, thienyl (or thiophenyl), furyl (or furanyl), pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, isoxazolyl, 1,2,3-triazolyl, tetrazolyl, 1,2,3- thiadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-triazolyl, 1,2,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,3,4- triazolyl, 1,3,4-thiadiazolyl, 1,3,4-oxadiazolyl and l,2-dihydro-l,2-azaborine, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, azolyl, triazolyl, thiadiazolyl, quinolinyl, isoquinolinyl, indolyl, benzothiophenyl, benzofuranyl, benzisoxazolyl, imidazofl, 2-b]thiazolyl, purinyl, triazinyl, thieno[3,2-b]pyridinyl, imidazo[l,2-a]pyridinyl, 1,5-naphthyridinyl, 1H- pyrazolo[4,3-b]pyridinyl, triazolo[4,3-a]pyridinyl, lH-pyrrolo[3,2-b]pyridinyl, 1H- pyrrolo[2,3-b]pyridinyl, pyrazolo[l,5-a]pyridinyl, indazolyl, and the like. The term “heteroaryl” is understood to include deuterated analogs of the heteroaryl groups as defined herein, including but not limited to, groups such as perdeuteropyridinyl, perdeuteropyrazinyl, perdeuteropyrimidinyl, and the like.

[0899] As used herein, “heterocycloalkyl” refers to monocyclic or polycyclic heterocycles having at least one non-aromatic ring (saturated or partially unsaturated ring), wherein one or more of the ring-forming carbon atoms of the heterocycloalkyl is replaced by a heteroatom selected from N, O, S, and B, and wherein the ring-forming carbon atoms and heteroatoms of a heterocycloalkyl group can be optionally substituted by one or more oxo or sulfido (e.g., C(O), S(O), C(S), or S(O)2, etc.). When a ring -forming carbon atom or heteroatom of a heterocycloalkyl group is optionally substituted by one or more oxo or sulfide, the O or S of said group is in addition to the number of ring -forming atoms specified herein (e.g., a 1- methyl-6-oxo-l,6-dihydropyridazin-3-yl is a 6-membered heterocycloalkyl group, wherein a ring-forming carbon atom is substituted with an oxo group, and wherein the 6-membered heterocycloalkyl group is further substituted with a methyl group). Heterocycloalkyl groups include monocyclic and polycyclic (e.g, having 2 fused rings) systems. Included in heterocycloalkyl are monocyclic and polycyclic 3 to 10, 4 to 10, 5 to 10, 4 to 7, 5 to 7, or 5 to 6 membered heterocycloalkyl groups. Heterocycloalkyl groups can also include spirocycles and bridged rings (e.g., a 5 to 10 membered bridged biheterocycloalkyl ring having one or more of the ring-forming carbon atoms replaced by a heteroatom independently selected from N, O, S, and B). The heterocycloalkyl group can be attached through a ring-forming carbon atom or a ring -forming heteroatom. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyl group contains 0 to 2 double bonds. The term “heterocycloalkyl” is understood to include deuterated analogs of the heterocycloalkyl groups as defined herein, including but not limited to, groups such as perdeuteroazetidinyl, perdeuteropyrrolidinyl, perdeuteropiperidinyl, and the like.

[0900] Also included in the definition of heterocycloalkyl are moieties that have one or more aromatic rings fused (i. e. , having a bond in common with) to the non-aromatic heterocyclic 54057 -0028 WO 1 / SNV0021-W01 PATENT ring, for example, benzo or thienyl derivatives of piperidine, morpholine, azepine, etc. A heterocycloalkyl group containing a fused aromatic ring can be attached through any ring- forming atom including a ring -forming atom of the fused aromatic ring.

[0901] In some embodiments, the heterocycloalkyl group contains 3 to 10 ring -forming atoms, 4 to 10 ring -forming atoms, 4 to 8 ring -forming atoms, 3 to 7 ring -forming atoms, or 5 to 6 ring -forming atoms. In some embodiments, the heterocycloalkyl group has 1 to 4 heteroatoms, 1 to 3 heteroatoms, 1 to 2 heteroatoms or 1 heteroatom. In some embodiments, the heterocycloalkyl is a monocyclic 4-6 membered heterocycloalkyl having 1 or 2 heteroatoms independently selected from N, O, S and B and having one or more oxidized ring members. In some embodiments, the heterocycloalkyl is a monocyclic or bicyclic 5-10 membered heterocycloalkyl having 1, 2, 3, or 4 heteroatoms independently selected from N, O, S, and B and having one or more oxidized ring members. In some embodiments, the heterocycloalkyl is a monocyclic or bicyclic 5 to 10 membered heterocycloalkyl having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S and having one or more oxidized ring members. In some embodiments, the heterocycloalkyl is a monocyclic 5 to 6 membered heterocycloalkyl having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S and having one or more oxidized ring members.

[0902] Example heterocycloalkyl groups include pyrrolidin-2-one (or 2-oxopyrrolidinyl), l,3-isoxazolidin-2-one, pyranyl, tetrahydropyran, oxetanyl, azetidinyl, morpholino, thiomorpholino, piperazinyl, tetrahydrofuranyl, tetrahydrothienyl, piperidinyl, pyrrolidinyl, isoxazolidinyl, isothiazolidinyl, pyrazolidinyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, azepanyl, 1,2,3,4-tetrahydroisoquinoline, tetrahydrothiopheneyl, tetrahydrothiopheneyl 1,1- dioxide, benzazapene, azabicyclo[3.1.0]hexanyl, diazabicyclo[3.1.0]hexanyl, oxobicyclo [2.1. l]hexanyl, azabicyclo [2.2. l]heptanyl, diazabicyclo [2.2. l]heptanyl, azabicyclo[3. 1. l]heptanyl, diazabicyclo [3.1. l]heptanyl, azabicyclo[3.2. l]octanyl, diazabicyclo [3.2. l]octanyl, oxobicyclo [2.2.2] octanyl, azabicyclo[2.2.2]octanyl, azaadamantanyl, diazaadamantanyl, oxo-adamantanyl, azaspiro[3.3]heptanyl, 2- azaspiro[3.3]heptanyl, diazaspiro[3.3]heptanyl, azaspiro[3.5]nonanyl, 7-azaspiro[3.5]nonanyl, oxo-azaspiro[3.3]heptanyl, azaspiro[3.4]octanyl, diazaspiro[3.4]octanyl, oxo- azaspiro[3.4]octanyl, azaspiro[2.5]octanyl, diazaspiro[2.5]octanyl, azaspiro [4.4] nonanyl, diazaspiro[4.4]nonanyl, oxo-azaspiro[4.4]nonanyl, azaspiro [4.5 ]decanyl, diazaspiro[4.5]decanyl, diazaspiro[4.4]nonanyl, oxo-diazaspiro[4.4]nonanyl, oxo- dihydropyridazinyl, oxo-2,6-diazaspiro[3.4]octanyl, oxohexahydropyrrolo[l,2-a]pyrazinyl, 3- oxopiperazinyl, oxo-pyrrolidinyl, oxo-pyridinyl, and the like.

[0903] As used herein, “C0.pcycloalkyl-Cn-malkyl-” refers to a group of formula cycloalkylalkylene-, wherein the cycloalkyl has o to p carbon atoms and the alkylene linking group has 54057 -0028 WO 1 / SNV0021-W01 PATENT n to m carbon atoms. The term “C0.pcycloalkyl-Cn-malkyl-” is understood to include deuterated analogs of the cycloalkyl and / or alkyl moieties of the C0.pcycloalkyl-Cn-malkylgroups as defined herein.

[0904] As used herein “C0.paryl-Cn-malkyl-” refers to a group of formula aryl-alkylene-, wherein the aryl has o to p carbon atoms and the alkylene linking group has n to m carbon atoms. The term “C0.paryl-Cn-malkyl-” is understood to include deuterated analogs of the aryl and / or alkyl moieties of the C0.paryl-Cn-malkyl- groups as defined herein. Example C0.paryl- Cn-m alkyl- groups include, but are not limited to, phenyl-CFE- (z.e., benzyl).

[0905] As used herein, “heteroaryl-Cn-malkyl-” refers to a group of formula heteroarylalkylene-, wherein alkylene linking group has n to m carbon atoms. The term “heteroaryl-Cn-malkyl-” is understood to include deuterated analogs of the heteroaryl and / or alkyl moieties of the heteroaryl-Cn-m alkyl- groups as defined herein.

[0906] As used herein “heterocycloalkyl -Cn-malkyl-” refers to a group of formula heterocycloalkyl-alkylene-, wherein alkylene linking group has n to m carbon atoms. The term “heterocycloalkyl -Cn-malkyl-” is understood to include deuterated analogs of the heterocycloalkyl and / or alkyl moieties of the heterocycloalkyl -Cn-malkyl- groups as defined herein.

[0907] As used herein, an “alkyl linking group” or “alkylene linking group” is a bivalent straight chain or branched alkyl linking group (“alkylene group”). For example, “C0.pcycloalkyl-Cn-m alkyl-”, “C0.paryl-Cn-malkyl-”, “phenyl-Cn-malkyl-”, “heteroaryl-Cn-malkyl-”, and “heterocycloalkyl-Cn-m alkyl-” contain alkyl linking groups. Examples of “alkyl linking groups” or “alkylene groups” include methylene, ethan- 1,1 -diyl, ethan- 1,2-diyl, propan-1, 3- dilyl, propan- 1,2-diyl, propan- 1,1 -diyl and the like. The terms “alkyl linking group” and “alkylene linking group” are understood to include deuterated analogs of the alkylene groups as defined herein.

[0908] As used herein, a “haloalkyl linking group” or “haloalkylene linking group” is a bivalent straight chain or branched haloalkyl linking group (“haloalkylene group”). Example haloalkylene groups include -CF2-, -C2F4-, -CHF-, -CCI2-, -CHC1-, -C2CI4-, and the like. The terms “haloalkyl linking group” and “haloalkylene linking group” are understood to include deuterated analogs of the haloalkylene groups as defined herein.

[0909] As used herein, a “cycloalkyl linking group” or “cycloalkylene linking group” is a bivalent straight chain or branched cycloalkyl linking group (“cycloalkylene group”). Examples of “cycloalkyl linking groups” or “cycloalkylene groups” include cyclopropy-1,1,- diyl, cyclopropy- 1,2-diyl, cyclobut-l,3,-diyl, cyclopent-1, 3, -diyl, cyclopent- 1,4, -diyl, cyclohex- 1,2, -diyl, cyclohex-1, 3, -diyl, cyclohex- 1,4, -diyl, and the like. The terms “cycloalkyl 54057 -0028 WO 1 / SNV0021-W01 PATENT linking group” and “cycloalkylene linking group” are understood to include deuterated analogs of the cycloalkylene groups as defined herein.

[0910] As used herein, a “heterocycloalkyl linking group” or “heterocycloalkylene linking group” is a bivalent straight chain or branched heterocycloalkyl linking group (“heterocycloalkylene group”). Examples of “heterocycloalkyl linking groups” or “heterocycloalkylene groups” include azetidin-l,2-diyl, azetidin- 1,3 -diyl, pyrrolidin-l,2-diyl, pyrrolidin-l,3-diyl, pyrrolidin-2,3-diyl, piperidin-l,2-diyl, piperidin-l,3-diyl, piperidin-1,4- diyl, piperidin-2,3-diyl, piperidin-2,4-diyl, and the like. The terms “heterocycloalkyl linking group” and “heterocycloalkylene linking group” are understood to include deuterated analogs of the heterocycloalkylene groups as defined herein.

[0911] As used herein, a “heteroaryl linking group” or “heteroarylene linking group” is a bivalent straight chain or branched heteroaryl linking group (“heteroarylene group”). Examples of “heteroaryl linking groups” or “heteroarylene groups” include pyrazol-l,3-diyl, imidazol- 1,2, -diyl, pyridin-2,3-diyl, pyridin-2,4-diyl, pyridin-3,4-diyl, and the like. The terms “heteroaryl linking group” and “heteroarylene linking group” are understood to include deuterated analogs of the heteroarylene groups as defined herein.

[0912] At certain places, the definitions or embodiments refer to specific rings (e.g., an azetidine ring, a pyridine ring, etc.). Unless otherwise indicated, these rings can be attached to any ring member provided that the valency of the atom is not exceeded. For example, an azetidine ring may be attached at any position of the ring, whereas a pyridin-3-yl ring is attached at the 3 -position.

[0913] As used herein, the term “oxo” refers to an oxygen atom (z.e., =0) as a divalent substituent, forming a carbonyl group when attached to a carbon (e.g., C=O or C(O)), or attached to a nitrogen or sulfur heteroatom forming a nitroso, sulfinyl, or sulfonyl group.

[0914] As used herein, the term “independently selected from” means that each occurrence of a variable or substituent (e.g., each RG) , are independently selected at each occurrence from the applicable list.

[0915] The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present disclosure that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present disclosure are 54057 -0028 WO 1 / SNV0021-W01 PATENT described and may be isolated as a mixture of isomers or as separated isomeric forms. In some embodiments, the compound has the (R) -configuration. In some embodiments, the compound has the (S)-configuration. The Formulas (e.g., Formula I, Formula II, etc.) provided herein include stereoisomers of the compounds.

[0916] Resolution of racemic mixtures of compounds can be carried out by any of numerous methods known in the art. An example method includes fractional recrystallizaion using a chiral resolving acid which is an optically active, salt-forming organic acid. Suitable resolving agents for fractional recrystallization methods are, for example, optically active acids, such as the D and L forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid or the various optically active camphorsulfonic acids such as P- camphorsulfonic acid. Other resolving agents suitable for fractional crystallization methods include stereoisomerically pure forms of a-methylbenzylamine (e.g., S and R forms, or diastereomerically pure forms), 2-phenylglycinol, norephedrine, ephedrine, N- methylephedrine, cyclohexylethylamine, 1,2-diaminocyclohexane, and the like.

[0917] Resolution of racemic mixtures can also be carried out by elution on a column packed with an optically active resolving agent (e.g., dinitrobenzoylphenylglycine). Suitable elution solvent composition can be determined by one skilled in the art.

[0918] Compounds provided herein also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone - enol pairs, amide - imidic acid pairs, lactam - lactim pairs, enamine - imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1H- and 3H-imidazole, 1H-, 2H- and 4H- 1,2,4-triazole, 1H- and 2H- isoindole, 2-hydroxypyridine and 2-pyridone, and 1H- and 2H- pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution.

[0919] All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g. hydrates and solvates) or can be isolated.

[0920] In some embodiments, preparation of compounds can involve the addition of acids or bases to affect, for example, catalysis of a desired reaction or formation of salt forms such as acid addition salts.

[0921] In some embodiments, the compounds provided herein, or salts thereof, are substantially isolated. By “substantially isolated” is meant that the compound is at least partially or substantially separated from the environment in which it was formed or detected. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0922] Partial separation can include, for example, a composition enriched in the compounds provided herein. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compounds provided herein, or salt thereof.

[0923] The term “compound” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted. Compounds herein identified by name or structure as one particular tautomeric form are intended to include other tautomeric forms unless otherwise specified.

[0924] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0925] The present application also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the present disclosure include the conventional nontoxic salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present disclosure can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, non-aqueous media like ether, ethyl acetate, alcohols (e.g., methanol, ethanol, iso-propanol, or butanol) or acetonitrile (ACN) are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa., 1985, p. 1418 and Journal of Pharmaceutical Science, 66, 2 (1977), each of which is incorporated herein by reference in its entirety.

[0926] Synthesis

[0927] Compounds of the invention, including salts thereof, can be prepared using known organic synthesis techniques and according to various possible synthetic routes. Example 54057 -0028 WO 1 / SNV0021-W01 PATENT synthetic methods for preparing compounds of the invention are provided in the Schemes below.

[0928] Compounds of Formula I, such as compounds of formula 1-19, can be synthesized, for example, using a process shown in Scheme I. Compound 1-1 can be converted to 1-3 via condensation with 1-2. 1-3 can then be converted to 1-5 via Reformatsky reaction with 1-4.

[0929] Treating 1-5 with HC1 can lead to 1-6. Intermediate 1-8 can be obtained by treating 1-6 with I- 7. 1-8 can be reduced to the aldehyde intermediate 1-9 with suitable reagent (e.g., DIABL-H). Treating 1-9 with TMSCN and Znl2can lead to 1-10. Treating 1-10 with reductant (e.g., SnC’E) leads to the intermediate 1-11. Treating 1-11 with diphenylphosphoryl azide under Mitsunobu reaction condition, followed by a reduction affords 1-12. Alkylation of 1-12 with I- 13 results in 1-14. 1-14 can be protected with BOC2O to give 1-15. 1-16 can be obtained via treating 1-15 with suitable base (e.g., NaH). Deprotection of 1-16 affords 1-17. A cascade transformation leads to 1-18 via treating 1-17 with metal mediated carbonylation reaction. 1-18 is converted into compound with formula 1-19 via suitable reactions (e.g., transition metal- catalyzed cross-coupling reactions).

[0930] 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0931] Compounds of Formula I, such as compounds of formula 11-15, can be synthesized, for example, using a process shown in Scheme II. Compound 1-1 can be converted to II-l via Corey-Chaykovsky reaction using suitable reagent (e.g., trimethylsulfoxonium iodide). Treating II-l with NaNs followed by reduction with PPhs leads to II-2. Protection of II- 2 affords II-3. Treating II-3 with diphenyl phosphoryl azide under Mitsunobu reaction condition, followed by reduction affords II-4. Protection of II-4 leads to II-5, which can be alkylated with suitable reagents to afford II-6 (e.g., ethyl 2-bromoacetate). The protection 54057 -0028 WO 1 / SNV0021-W01 PATENT group can be removed from II-6, then the intermediate can cyclize to afford II-7 under thermal condition. Removal of the nosyl group and reprotection of amine affords II-8. Treating II-8 with 1-7 afford II-9, which can be reduced and condensed to afford 11-10. Intermediate 11-11 can be obtained by treating 11-10 with palladium mediated cross coupling reaction with suitable reagent (e.g., tributyl(vinyl)tin). 11-11 can be converted to 11-12 via an oxidative cleavage (e.g, OsC>4 and NalCE) followed by a reduction (e.g., NaBH ). 11-13 can be obtained by treating 11-12 with suitable reagent (e.g., SOCI2). Cyclization of 11-13 under thermal condition results in 11-14, which can then be converted to 11-15 via suitable reactions (e.g., transition metal -catalyzed cross-coupling reactions).

[0932] Scheme II. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0933] The reactions for preparing compounds of the invention can be carried out in suitable solvents which can be readily selected by one of skill in the art of organic synthesis. Suitable solvents can be substantially nonreactive with the starting materials (reactants), the intermediates, or products at the temperatures at which the reactions are carried out, e.g. , temperatures which can range from the solvent's freezing temperature to the solvent's boiling temperature. A given reaction can be carried out in one solvent or a mixture of more than one solvent. Depending on the particular reaction step, suitable solvents for a particular reaction step can be selected by the skilled artisan.

[0934] Preparation of compounds of the invention can involve the protection and deprotection of various chemical groups. The need for protection and deprotection, and the selection of appropriate protecting groups, can be readily determined by one skilled in the art. The chemistry of protecting groups can be found, for example, in T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 3rd. Ed., Wiley & Sons, Inc., New York (1999), which is incorporated herein by reference in its entirety.

[0935] Reactions can be monitored according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g., ’H or13C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), or mass spectrometry, or by chromatography such as high performance liquid chromatography (HPLC) or thin layer chromatography.

[0936] The expressions, “ambient temperature,” “room temperature,” and “r.t ”, as used herein, are understood in the art, and refer generally to a temperature, e.g. a reaction temperature, that is about the temperature of the room in which the reaction is carried out, for example, a temperature from about 20 °C to about 30 °C.

[0937] Methods of Use

[0938] The present disclosure provides uses for compounds and compositions described herein. The compounds described herein can inhibit the activity of tumor necrosis factoralpha (TNFa). In some embodiments, provided compounds and compositions are for use in medicine (e.g., as therapy). In some embodiments, provided compounds and compositions are useful in treating a disease, disorder, or condition, wherein an underlying pathology is, wholly or partially, mediated by TNFa. In some embodiments, provided compounds and compositions are useful in research as, for example, analytical tools and / or control compounds in biological assays.

[0939] In autoimmune diseases, TNF-a is often overproduced, leading to chronic inflammation and tissue damage. For example, in rheumatoid arthritis, TNF-a contributes to synovial inflammation and joint destruction. Inflammatory bowel disease involves TNF-a- 54057 -0028 WO 1 / SNV0021-W01 PATENT driven inflammation of the gastrointestinal tract. Overexpression of TNF-a is also involved in the pathogenesis of psoriasis, a chronic inflammatory skin disorder characterized by hyperproliferation of keratinocytes and an influx of immune cells into the skin. In addition to above-mentioned diseases, overproduction of TNF-a is also implicated in many other human diseases related to chronic inflammation and cell apoptosis, particularly for some neurodegenerative diseases (see e.g., Nat. Rev. Immunol. 2023;23(5):289-303).

[0940] Therapeutic strategies targeting TNF-a, such as monoclonal antibodies (e.g., infliximab, adalimumab, golimumab, and certrolizumab) or receptor decoys (e.g., etanercept), have been effective in treating rheumatoid arthritis, inflammatory bowel disease, and psoriasis by reducing inflammation and mitigating tissue damage [see e.g, Pharmacol. Ther.

[0941] 2008; 117(2):244-79). These biologies have revolutionized the treatment of many autoimmune diseases and significantly improved clinical outcomes for many patients. However, use of these biologies is also associated with several significant issues (see e.g., Drug Discov.

[0942] Today. 2022;27( 1) :3 -7). First, patients may develop anti-drug antibodies that lead to diminished efficacy and drug failure. Second, TNF-a blockers can increase the risk of infections, which is presumably related to blockade of the TNFR2 that is involved in immune regulation. Third, TNF-a blockers can cause adverse reactions such as injection site reactions due to the immunogenicity of large immune complexes formed by TNF-a and the biologies. Finally, the high cost of TNF-a blockers can be a barrier for many patients, limiting accessibility and long-term treatment sustainability.

[0943] In addition to biologies, small molecule inhibitors have also been explored for blockade of the TNF-a signaling. Recent progress in this area has shown promising advancements, offering potential alternatives to biological TNF-a inhibitors (see e.g., Drug Discov. Today. 2023;28(6): 103575). Unlike biologies, small molecules can be administered orally and are generally less costly to produce, making them more accessible to patients. One significant development in this area is the identification of small molecules that disrupt the TNF-a trimer, preventing its binding to TNF receptors (see e.g., Science.

[0944] 2005;310(5750): 1022-5). These molecules work by stabilizing TNF-a in an inactive conformation, thereby blocking its ability to initiate inflammatory signaling. Some other small molecule inhibitors have also been designed to lock TNF-a in an inactive conformation that cannot initiate downstream chronic inflammatory signal (see e.g., Nat. Commun.

[0945] 2019; 10( 1) : 5795) . Despite these advances, it remains challenging to discover a potent and effective drug -like small molecule inhibitor of TNF-a for autoimmune and inflammatory diseases. Thus, there is a need for developing new molecular inhibitors of TNFa.

[0946] Accordingly, in some embodiments, the present disclosure provides methods of administering provided compounds or compositions to a subject in need thereof. In some 54057 -0028 WO 1 / SNV0021-W01 PATENT embodiments, the present disclosure provides methods of administering provided compounds or compositions to a subject suffering from or susceptible to a disease, disorder, or condition associated with TNFa. In some embodiments, the present disclosure provides methods of administering provided compounds or compositions to a subject suffering from or susceptible to a disease, disorder, or condition, wherein an underlying pathology is, wholly or partially, mediated by TNFa.

[0947] When used as a single agent for monotherapy, the compounds, salts, and compositions of the present disclosure are expected to suppress overexpression of TNF-a induced production of proinflammatory cytokines and chemokines including IL1, IL6, IL8, IL12, IL17, IL22, IL23, MCP1, IFN-y, and GM-CSF etc. Overproduction of these proinflammatory proteins play a pivotal role in the initiation and progression of a variety of autoimmune and chronic inflammatory conditions listed above. When used as a single agent for monotherapy, provided compounds and compositions of the present disclosure are expected to block TNF-a induced downstream signaling, inhibit immune cell activation, suppress cell apoptosis, and thereby help restore the balance between pro -inflammatory and anti-inflammatory pathways.

[0948] In some embodiments, the compounds provided herein are useful as TNFa inhibitors. In some embodiments, the present disclosure provides methods of inhibiting TNFa in a subject comprising administering a provided compound or composition. In some embodiments, the present disclosure provides methods of inhibiting TNFa in a biological sample comprising contacting the sample with a provided compound or composition.

[0949] In some embodiments, the present disclosure provides methods of treating a disease, disorder or condition associated with TNFa in a subject in need thereof, comprising administering to the subject a compound, salt, or composition of the disclosure. In some embodiments, a disease, disorder or condition is associated with mutation of TNFa. In some embodiments, the present disclosure provides methods of treating a disease, disorder or condition, wherein an underlying pathology is, wholly or partially, mediated by TNFa, in a subject in need thereof, comprising administering to the subject a provided compound or composition.

[0950] In some embodiments, the present disclosure provides methods of treating a variety of TNFa-dependent diseases and disorders. For example, in some embodiments the present disclosure provides methods of treating TNF-a overproduction related autoimmune and chronic inflammatory diseases, comprising administering a provided compound or composition to a subject in need thereof. Exemplary diseases include, but are not limited, to plaque psoriasis, rheumatoid arthritis (RA), psoriatic arthritis (PsA), Crohn’s disease (CD), ulcerative colitis (UC), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), 54057 -0028 WO 1 / SNV0021-W01 PATENT hidradenitis suppurativa (HS), uveitis, sarcoidosis, Behcet's disease, granulomatosis with polyangiitis, and neurodegenerative diseases associated with TNF-a related inflammation and apoptosis, including Alzheimer's disease, Parkinson's disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease, traumatic brain injury, and neuromyelitis optica spectrum disorder (NMOSD).

[0951] In some embodiments, provided herein is a method of increasing survival or progression-free survival in a patient, comprising administering a compound provided herein to the patient. In some embodiments, the patient has cancer. In some embodiments, the patient has a disease or disorder described herein. As used herein, progression-free survival refers to the length of time during and after the treatment of a solid tumor that a patient lives with the disease but it does not get worse. Progression-free survival can refer to the length of time from first administering the compound until the earlier of death or progression of the disease. Progression of the disease can be defined by RECIST v. 1. 1 (Response Evaluation Criteria in Solid Tumors), as assessed by an independent centralized radiological review committee. In some embodiments, administering of the compound results in a progression free survival that is greater than about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months, about 9 months, about 12 months, about 16 months, or about 24 months. In some embodiments, the administering of the compound results in a progression free survival that is at least about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months, about 9 months, or about 12 months; and less than about 24 months, about 16 months, about 12 months, about 9 months, about 8 months, about 6 months, about 5 months, about 4 months, about 3 months, or about 2 months. In some embodiments, the administering of the compound results in an increase of progression free survival that is at least about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, about 6 months, about 8 months, about 9 months, or about 12 months; and less than about 24 months, about 16 months, about 12 months, about 9 months, about 8 months, about 6 months, about 5 months, about 4 months, about 3 months, or about 2 months.

[0952] The present disclosure further provides a compound described herein, or a pharmaceutically acceptable salt thereof, for use in any of the methods described herein.

[0953] The present disclosure further provides use of a compound described herein, or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for use in any of the methods described herein.

[0954] As used herein, the term “cell” is meant to refer to a cell that is in vitro, ex vivo or in vivo. In some embodiments, an ex vivo cell can be part of a tissue sample excised from an organism such as a mammal. In some embodiments, an in vitro cell can be a cell in a cell 54057 -0028 WO 1 / SNV0021-W01 PATENT culture. In some embodiments, an in vivo cell is a cell living in an organism such as a mammal.

[0955] As used herein, the term “contacting” refers to the bringing together of indicated moieties in an in vitro system or an in vivo system. For example, “contacting” a TNFa with a compound described herein includes the administration of a compound described herein to an individual or patient, such as a human, having a TNFa, as well as, for example, introducing a compound described herein into a sample containing a cellular or purified preparation containing the TNFa.

[0956] As used herein, the term “individual” or “patient,” used interchangeably, refers to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans.

[0957] As used herein, the phrase “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent such as an amount of any of the solid forms or salts thereof as disclosed herein that elicits the biological or medicinal response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinician. An appropriate "effective" amount in any individual case may be determined using techniques known to a person skilled in the art.

[0958] The phrase “pharmaceutically acceptable” is used herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, immunogenicity or other problem or complication, commensurate with a reasonable benefit / risk ratio.

[0959] As used herein, the phrase “pharmaceutically acceptable carrier or excipient” refers to a pharmaceutically-acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, solvent, or encapsulating material. Excipients or carriers are generally safe, non-toxic and neither biologically nor otherwise undesirable and include excipients or carriers that are acceptable for veterinary use as well as human pharmaceutical use. In one embodiment, each component is “pharmaceutically acceptable” as defined herein. See, e.g., Remington: The Science and Practice of Pharmacy, 21st ed.; Lippincott Williams & Wilkins: Philadelphia, Pa., 2005; Handbook of Pharmaceutical Excipients, 6th ed.; Rowe et al., Eds.; The Pharmaceutical Press and the American Pharmaceutical Association: 2009; Handbook of Pharmaceutical Additives, 3rd ed.; Ash and Ash Eds.; Gower Publishing Company: 2007; Pharmaceutical Preformulation and Formulation, 2nd ed.; Gibson Ed.; CRC Press LLC: Boca Raton, Fla., 2009.

[0960] As used herein, the term “treating” or “treatment” refers to inhibiting the disease; for example, inhibiting a disease, condition or disorder in an individual who is experiencing or 54057 -0028 WO 1 / SNV0021-W01 PATENT displaying the pathology or symptomatology of the disease, condition or disorder (z.e., arresting further development of the pathology and / or symptomatology) or ameliorating the disease; for example, ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i. e. , reversing the pathology and / or symptomatology) such as decreasing the severity of disease.

[0961] In some embodiments, the compounds of the invention are useful in preventing or reducing the risk of developing any of the diseases referred to herein; e.g., preventing or reducing the risk of developing a disease, condition or disorder in an individual who may be predisposed to the disease, condition or disorder but does not yet experience or display the pathology or symptomatology of the disease.

[0962] It is appreciated that certain features of the disclosure, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment (while the embodiments are intended to be combined as if written in multiply dependent form). Conversely, various features of the disclosure which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination.

[0963] Combination Therapy

[0964] One or more additional therapeutic agents such as, for example, chemotherapeutics or other anti-cancer agents, anti-inflammatory agents, steroids, immunosuppressants, anesthetics (e.g. , for use in combination with a surgical procedure), or other agents useful for treating diseases associated with TNFa can be used in combination with the compounds and salts provided herein. The agents can be combined with the present compounds in a single dosage form, or the agents can be administered simultaneously or sequentially as separate dosage forms.

[0965] In some embodiments, a compound, salt, or composition of the present disclosure is administered as part of a combination therapy. As used herein, the term “combination therapy” refers to those situations in which a subject is simultaneously exposed to two or more therapeutic or prophylactic regimens (e.g., two or more therapeutic or prophylactic agents). Exemplary additional therapies include but are not limited to small molecules, biologies, and gene and cell therapies. In some embodiments, the two or more therapeutic agents are administered simultaneously. In some embodiments, the two or more therapeutic agents are administered sequentially.

[0966] In some embodiments, compound, salt, or composition of the present disclosure can be combined with other therapies for treatment of rheumatoid arthritis (RA). Exemplary 54057 -0028 WO 1 / SNV0021-W01 PATENT therapies include, but are not limited to, conventional disease-modifying antirheumatic drugs (DMARDs), biologies, targeted synthetic DMARDs (small molecules), and supportive treatments. Conventional DMARDs include methotrexate, sulfasalazine, leflunomide, and hydroxychloroquine etc. Biologic DMARDs include etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab and all those available biosimilars. Targeted synthetic DMARDs are mainly JAK inhibitors including tofacitinib, baricitinib, upadacitinib, and filgotinib. The compounds, salts, and compositions of the present disclosure can also be combined with nonsteroidal anti-inflammatory drugs (NSAIDs) including, but not limited to, ibuprofen, naproxen, and celecoxib, and the like. Other potential combination partners include, but are not limited to, tocilizumab, sarilumab, rituximab, abatacept, and anakinra.

[0967] In some embodiments, compound, salt, or composition of the present disclosure can be combined with other therapies for treatment of inflammatory bowel diseases (IBD). Exemplary therapies include, but are not limited to, conventional therapies, biologic therapies, small molecule therapies, and emerging and experimental therapies. Conventional therapies include, but are not limited to, sulfasalazine, mesalamine (5-ASA), olsalazine, balsalazide, prednisone, methylprednisolone, budesonide, hydrocortisone, azathioprine, 6 -mercaptopurine (6-MP), methotrexate, cyclosporine, and tacrolimus. Biologic therapies include, but are not limited to, infliximab, adalimumab, certolizumab pegol (e.g., for treatment of Crohn's disease), golimumab (e.g, for treatment of ulcerative colitis), natalizumab, vedolizumab, and ustekinumab. Small molecule therapies include, but are not limited to, JAK inhibitors. Emerging and experimental therapies include, but are not limited to, sphingosine- 1 -phosphate (SIP) receptor modulators, and JAK inhibitors including, but not limited to, tofacitinib, filgotinib, and upadacitinib. In addition, the compounds, salt, and compositions of the present disclosure can also be combined with additional other therapies including, but not limited to, stem cell therapy and fecal microbiota transplantation.

[0968] In some embodiments, a compound, salt, or composition of the present disclosure can be combined with other additional therapies for treatment of psoriasis. Exemplary therapies include, but are not limited to, topical treatments, systemic treatments, biologic therapies, and emerging and experimental therapies. Topical treatments include, but are not limited to, hydrocortisone, betamethasone, clobetasol, triamcinolone, calcipotriene, calcitriol, tazarotene, tacrolimus, and pimecrolimus. Systemic treatments include, but are not limited to, methotrexate, cyclosporine, and acitretin. Biologic therapies include, but are not limited to, etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab, and all those available biosimilars, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab. Emerging and experimental therapies include, but are not 54057 -0028 WO 1 / SNV0021-W01 PATENT limited to, JAK inhibitors and TYK2 inhibitors including, but not limited to, deucravacitinib, ropsacitinib, and brepocitinib.

[0969] Methods for the safe and effective administration of most of these agents are known to those skilled in the art. In addition, their administration is described in the standard literature.

[0970] In some embodiments, the additional therapeutic agent is administered simultaneously with a compound, salt, or composition provided herein. In some embodiments, the additional therapeutic agent is administered after administration of the compound, salt, or composition provided herein. In some embodiments, the additional therapeutic agent is administered prior to administration of the compound, salt, or composition provided herein. In some embodiments, the compound, salt, or composition provided herein is administered during a surgical procedure. In some embodiments, the compound, salt, or composition provided herein is administered in combination with an additional therapeutic agent during a surgical procedure.

[0971] As provided herein, the additional compounds, inhibitors, agents, etc. can be combined with the compounds, salts, or compositions provided herein in a single or continuous dosage form, or they can be administered simultaneously or sequentially as separate dosage forms.

[0972] Pharmaceutical Formulations and Dosage Forms

[0973] When employed as pharmaceuticals, the compounds of the invention can be administered in the form of pharmaceutical compositions which refers to a combination of a compound of the invention, or its pharmaceutically acceptable salt, and at least one pharmaceutically acceptable carrier. These compositions can be prepared in a manner well known in the pharmaceutical art, and can be administered by a variety of routes, depending upon whether local or systemic treatment is desired and upon the area to be treated. Administration may be topical (including ophthalmic and to mucous membranes including intranasal, vaginal and rectal delivery), pulmonary (e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal, intranasal, epidermal and transdermal), ocular, oral or parenteral. Methods for ocular delivery can include topical administration (eye drops), subconjunctival, periocular or intravitreal injection or introduction by balloon catheter or ophthalmic inserts surgically placed in the conjunctival sac. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal, or intramuscular injection or infusion; or intracranial, e.g., intrathecal or intraventricular, administration. Parenteral administration can be in the form of a single bolus dose, or may be, for example, by a continuous perfusion pump. Pharmaceutical compositions and formulations 54057 -0028 WO 1 / SNV0021-W01 PATENT for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable.

[0974] This invention also includes pharmaceutical compositions which contain, as the active ingredient, one or more of the compounds of the invention above in combination with one or more pharmaceutically acceptable carriers. In making the compositions of the invention, the active ingredient is typically mixed with an excipient, diluted by an excipient or enclosed within such a carrier in the form of, for example, a capsule, sachet, paper, or other container. When the excipient serves as a diluent, it can be a solid, semi-solid, or liquid material, which acts as a vehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), ointments containing, for example, up to 10 % by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injectable solutions, and sterile packaged powders.

[0975] In preparing a formulation, the active compound can be milled to provide the appropriate particle size prior to combining with the other ingredients. If the active compound is substantially insoluble, it can be milled to a particle size of less than 200 mesh. If the active compound is substantially water soluble, the particle size can be adjusted by milling to provide a substantially uniform distribution in the formulation, e.g. about 40 mesh.

[0976] The active compound can be effective over a wide dosage range and is generally administered in a pharmaceutically effective amount. It will be understood, however, that the amount of the compound actually administered will usually be determined by a physician, according to the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms, and the like.

[0977] For preparing solid compositions such as tablets, the principal active ingredient is mixed with a pharmaceutical excipient to form a solid pre -formulation composition containing a homogeneous mixture of a compound of the present invention. When referring to these pre-formulation compositions as homogeneous, the active ingredient is typically dispersed evenly throughout the composition so that the composition can be readily subdivided into equally effective unit dosage forms such as tablets, pills and capsules. This solid pre-formulation is then subdivided into unit dosage forms of the type described above.

[0978] The tablets or pills of the present invention can be coated or otherwise compounded to provide a dosage form affording the advantage of prolonged action. For example, the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former. The two components can be separated by an enteric 54057 -0028 WO 1 / SNV0021-W01 PATENT layer which serves to resist disintegration in the stomach and permit the inner component to pass intact into the duodenum or to be delayed in release.

[0979] The liquid forms in which the compounds and compositions of the present invention can be incorporated for administration orally or by injection include aqueous solutions, suitably flavored syrups, aqueous or oil suspensions, and flavored emulsions with edible oils.

[0980] The compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable, aqueous or organic solvents, or mixtures thereof, and powders. The liquid or solid compositions may contain suitable pharmaceutically acceptable excipients as described supra. In some embodiments, the compositions are administered by the oral or nasal respiratory route for local or systemic effect. Compositions in can be nebulized by use of inert gases. Nebulized solutions may be breathed directly from the nebulizing device or the nebulizing device can be attached to a face masks tent, or intermittent positive pressure breathing machine. Solution, suspension, or powder compositions can be administered orally or nasally from devices which deliver the formulation in an appropriate manner.

[0981] The amount of compound or composition administered to a patient will vary depending upon what is being administered, the purpose of the administration, such as prophylaxis or therapy, the state of the patient, the manner of administration, and the like. In therapeutic applications, compositions can be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications. Effective doses will depend on the disease condition being treated as well as by the judgment of the attending clinician depending upon factors such as the severity of the disease, the age, weight and general condition of the patient, and the like.

[0982] The compositions administered to a patient can be in the form of pharmaceutical compositions described above. These compositions can be sterilized by conventional sterilization techniques, or may be sterile filtered. Aqueous solutions can be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile aqueous carrier prior to administration. The pH of the compound preparations typically will be between 3 and 11, more preferably from 5 to 9 and most preferably from 7 to 8. It will be understood that use of certain of the foregoing excipients, carriers, or stabilizers will result in the formation of pharmaceutical salts.

[0983] The therapeutic dosage of the compounds of the present invention can vary according to, for example, the particular use for which the treatment is made, the manner of administration of the compound, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of a compound of the invention in a pharmaceutical composition can vary depending upon a number of factors including dosage, chemical characteristics (e.g., hydrophobicity), and the route of administration. The dosage is 54057 -0028 WO 1 / SNV0021-W01 PATENT likely to depend on such variables as the type and extent of progression of the disease or disorder, the overall health status of the particular patient, the relative biological efficacy of the compound selected, formulation of the excipient, and its route of administration. Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems.

[0984] The compositions of the disclosure can further include one or more additional pharmaceutical agents such as a chemotherapeutic, steroid, anti-inflammatory compound, or immunosuppressant, examples of which are provided herein.

[0985] Labeled Compounds and Assay Methods

[0986] Another aspect of the present invention relates to fluorescent dye, spin label, heavy metal or radio-labeled compounds of the invention that would be useful not only in imaging but also in assays, both in vitro and in vivo, for localizing and quantitating the TNFa in tissue samples, including human, and for identifying TNFa by inhibition binding of a labeled compound. Accordingly, the present invention includes TNFa cellular assays that contain such labeled compounds.

[0987] The present invention further includes isotopically-labeled compounds of the invention. An “isotopically” or “radio -labeled” compound is a compound of the invention where one or more atoms are replaced or substituted by an atom having an atomic mass or mass number different from the atomic mass or mass number typically found in nature (i. e. , naturally occurring). Suitable radionuclides that may be incorporated in compounds of the present invention include but are not limited to2H (also written as D for deuterium),3H (also written as T fortritium),nC,13C,14C,13N,15N,15O,17O,18O,18F,35S,36C1,82Br,75Br,76Br,77Br,1231,1241,125I and131I. The radionuclide that is incorporated in the instant radio-labeled compounds will depend on the specific application of that radio -labeled compound. For example, for in vitro FGFR enzyme labeling and competition assays, compounds that incorporate3H,14C,82Br,1251 ,131I, or35S will generally be most useful. For radio-imaging applicationsnC,18F,125I,123I,124I,131I,75Br,76Br or77Br will generally be most useful.

[0988] One or more constituent atoms of the compounds presented herein can be replaced or substituted with isotopes of the atoms in natural or non-natural abundance. In some embodiments, one or more atoms are replaced or substituted by deuterium. For example, one or more hydrogen atoms in a compound of the present disclosure can be replaced by deuterium atoms (e.g., one or more hydrogen atoms of a Ci-6 alkyl group of Formula I can be optionally substituted with deuterium atoms, such as -CDs being substituted for -CHs). In some embodiments, alkyl groups of the disclosed Formulas (e.g., the compound of any of Formulas I-VIIIc) can be perdeuterated. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0989] In some embodiments, the compound provided herein (e.g., the compound of any of Formulas I-VIIIc), or a pharmaceutically acceptable salt thereof, comprises at least one deuterium atom.

[0990] In some embodiments, the compound provided herein (e.g., the compound of any of Formulas I-VIIIc), or a pharmaceutically acceptable salt thereof, comprises two or more deuterium atoms.

[0991] In some embodiments, the compound provided herein (e.g., the compound of any of Formulas I-VIIIc), or a pharmaceutically acceptable salt thereof, comprises three or more deuterium atoms.

[0992] In some embodiments, for a compound provided herein (e.g., the compound of any of Formulas I-VIIIc), or a pharmaceutically acceptable salt thereof, all of the hydrogen atoms are replaced by deuterium atoms (z.e., the compound is “perdeuterated”).

[0993] It is understood that a “radio-labeled ” or “labeled compound” is a compound that has incorporated at least one radionuclide. In some embodiments the radionuclide is selected from the group consisting of3H,14C,1251 ,35S and82Br.

[0994] Synthetic methods for including isotopes into organic compounds are known in the art (Deuterium Labeling in Organic Chemistry by Alan F. Thomas (New York, N.Y., Appleton-Century-Crofts, 1971; The Renaissance of H / D Exchange by Jens Atzrodt, Volker Derdau, Thorsten Fey and Jochen Zimmermann, Angew. Chem. Int. Ed. 2007, 7744-7765; The Organic Chemistry of Isotopic Labelling by James R. Hanson, Royal Society of Chemistry, 2011). Isotopically labeled compounds can be used in various studies such as NMR spectroscopy, metabolism experiments, and / or assays.

[0995] Substitution with heavier isotopes, such as deuterium, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements, and hence may be preferred in some circumstances, (see e.g., A. Kerekes et. al. J. Med. Chem. 2011, 54, 201-210; R. Xu et. al. J. Label Compd. Radiopharm. 2015, 58, 308-312). In particular, substitution at one or more metabolism sites may afford one or more of the therapeutic advantages.

[0996] A radio-labeled compound of the invention can be used in a screening assay to identify / evaluate compounds. In general terms, a newly synthesized or identified compound (z.e., test compound) can be evaluated for its ability to reduce binding of the radio-labeled compound of the invention to the TNFa. Accordingly, the ability of a test compound to compete with the radio-labeled compound for binding to the TNFa directly correlates to its binding affinity.

[0997] Kits 54057 -0028 WO 1 / SNV0021-W01 PATENT

[0998] The present invention also includes pharmaceutical kits useful, for example, in the treatment or prevention of TNFa-associated diseases or disorders referred to herein which include one or more containers containing a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention. Such kits can further include, if desired, one or more of various conventional pharmaceutical kit components, such as, for example, containers with one or more pharmaceutically acceptable carriers, additional containers, etc., as will be readily apparent to those skilled in the art. Instructions, either as inserts or as labels, indicating quantities of the components to be administered, guidelines for administration, and / or guidelines for mixing the components, can also be included in the kit.

[0999] The invention will be described in greater detail by way of specific examples. The following examples are offered for illustrative purposes, and are not intended to limit the invention in any manner. Those of skill in the art will readily recognize a variety of non- critical parameters which can be changed or modified to yield essentially the same results. The compounds of the Examples were found to be inhibitors of TNFa as described below.

[1000] EXAMPLES

[1001] Experimental procedures for compounds of the invention are provided below. Preparatory LC-MS purifications of some of the compounds prepared were performed on Waters mass directed fractionation systems. The basic equipment setup, protocols, and control software for the operation of these systems have been described in detail in the literature. See e.g. “Two-Pump At Column Dilution Configuration for Preparative LC-MS”, K. Blom, J. Combi, ('hem.. 4, 295 (2002); “Optimizing Preparative LC-MS Configurations and Methods for Parallel Synthesis Purification”, K. Blom, R. Sparks, J. Doughty, G. Everlof, T. Haque, A. Combs, J. Combi. Chem., 5, 670 (2003); and "Preparative LC-MS Purification: Improved Compound Specific Method Optimization", K. Blom, B. Glass, R. Sparks, A. Combs, J. Combi. Chem., 6, 874-883 (2004). The compounds separated were typically subjected to analytical liquid chromatography mass spectrometry (LCMS) for purity check.

[1002] Some of the compounds prepared were also separated on a preparative scale by reverse-phase high performance liquid chromatography (RP-HPLC) with MS detector or flash chromatography (silica gel) as indicated in the Examples.

[1003] Intermediate 1. 5-(5-Bromopyrimidin-2-yl)-5-methylimidazolidine-2, 4-dione 54057 -0028 WO 1 / SNV0021-W01 PATENT

[1004] To the l-(5-bromopyrimidin-2-yl)ethan-l-one (133.5 mg, 0.66 mmol) in a 1 to 1 mixture of EtOH and water was added sodium cyanide (42.3 mg, 0.86 mmol) and ammonium carbonate (485 mg, 5.05 mmol) at rt. The resulting mixture was heated at 45 °C for 8 hours. Upon completion, the reaction was diluted with water, cooled to 0 °C, to which was added 2M HC1 to acidify the reaction mixture till no more gas was generated. The resulting lightyellow solution was stirred at 0 °C for another 30 min to give beige color solid. The solid was collected by filtration to give 5-(5-bromopyrimidin-2-yl)-5-methyl-imidazolidine-2, 4-dione (160 mg, 88.9%). LCMS calculated for C8H8BrN4O2(M+H)+m / z = 271.0; found 271.0.

[1005] Intermediate 2. 3-(5-Bromopyrimidin-2-yl)tetrahydrofuran-3-ol

[1006] To the solution of 5 -bromo-2 -iodo-pyrimidine (2.12 g, 7.44 mmol) in DCM (40 mL) at -78 °C was added 2.5 M n-butyllithium in hexanes (3.87 mL, 9.67 mmol) dropwise, after 30 min, a solution oftetrahydrofuran-3-one (744 mL, 9.67 mmol) in DCM (5 mL) was added dropwise at -78 °C. After 1 h, the reaction was quenched with sat. NH4CI solution. The resulting mixture slowly warmed up to rt. The mixture was diluted with ethyl acetate (50 mL *2), combined organic layer was washed with brine, dried through sodium sulfate. The crude was purified by FCC, eluting from 0-100% EA / Hexanes to give desired product was yellow oil. LCMS calculated for C8HioBrN2C>2 (M+H)+m / z = 245.0; found 245.0.

[1007] Intermediates 3-8.

[1008] The following Intermediates 3-8 in Table 1 were prepared similarly as described for Intermediate 2. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[1009] Table 1.

[1010] Intermediate 9. N-(3-(5-Bromopyrimidin-2-yl)tetrahydrofuran-3-yl)-2-methylpropane- 2-sulfinamide

[1011] Step 1 : N-(dihydrofuran-3(2H)-ylidene)-2-methylpropane-2-sulfinamide 54057 -0028 WO 1 / SNV0021-W01 PATENT

[1012] To the THF solution of tetrahydrofuran-3-one (3.94 g, 45.77 mmol) was added 2- methylpropane-2-sulfmamide (5.55 g, 45.77 mmol) and titanium isopropoxide (14.9 m , 14.31 g, 50.34 mmol) at rt. The resulting mixture was heated at 60 °C overnight. Upon completion of the reaction, the mixture was cooled to rt, diluted with EtOAc (40 m ). To the above mixture was added water to give white precipitate. The precipitate was removed by filtering through Celite. The organic layer of filtrate was separated, washed with brine, dried with sodium sulfate. The crude was purified with FCC, eluting from 0-20% EA / DCM to give desired product (4.10 g, 47.3 %). ECMS calculated for CsHieNChS (M+H)+m / z = 190.1; found 190.1.

[1013] Step 2: N-(dihydrofuran-3(2H)-ylidene)-2-methylpropane-2-sulfinamide

[1014] To the solution of 5 -bromo-2 -iodo-pyrimidine (800 mg, 2.81 mmol) in DCM (20.0 v) at -78 °C was added 2.5 M n-butyllithium in hexanes (1460 pb. 3.65 mmol) dropwise, after 30 min, a solution of (E)-A'-(dihydrofuran-3(2 / / )-ylidcnc)-2-mcthylpropanc-2-siilfinamidc (585 mg, 3.09 mmol) in DCM (5.0 v) was added dropwise at -78 °C. After 1 h, the reaction was quenched with sat. NH4CI solution. The resulting mixture slowly warmed up to rt. The mixture was diluted with ethyl acetate (50 mb *2), combined organic layer was washed with brine, dried through sodium sulfate. The crude was purified with FCC, eluting from 0-100% EA / Hexanes to give desired product as a yellow oil, LCMS calculated for CnHigBrNsCES (M+H)+m / z = 348.0; found 348.0.

[1015] Intermediate 10. tert-Butyl (2-(5-bromopyrimidin-2-yl)propan-2-yl)carbamate

[1016] 2-(5-Bromopyrimidin-2-yl)propan-2-ol (1.00 g, mmol) in ACN (10.0 mb) was added cone. H2SO4 (1.28 mb), the reaction was stirred at 60 °C for 4 h. Water (1.0 mb) was added and then the reaction was stirred at 60 °C overnight. The mixture was cooled down and poured into 60 mb cold water which was extracted with ether (30 mb) three times. The aqueous was then dried and the crude product (~ 0.4 g) was dissolved in ethanol (6.0 mb) and then NEts (0.8 mb) was added followed by BOC2O (0.50 g) and then stirred for 2 h. The solvent was concentrated, and the crude product was purified by column to afford the desired product as a white solid. ECMS calculated for CnHigBrNsCh (M+H)+m / z = 316.1; found 316.1. 54057 -0028 WO 1 / SNV0021-W01 PATENT

[1017] Intermediate 11. l-(5-Bromopyrimidin-2-yl)-3-(((tert- butyldimethylsilyl)oxy)methyl)cyclobutyl acetate

[1018] To the solution of methyl 3 -oxocyclobutane -1 -carboxylate (22.5 g, 197 mmol) in MeOH (250 mL) was added trimethyl orthoformate (130 mL) and PTSA (3.25g, 19.7 mmol). The reaction solution was stirred at 80 °C for 2h. After cooled to rt, the reaction was concentrated under vacuum. The residue was diluted with EtOAc and washed with sat. NaHCOs and sat. NaCl, then dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was used directly in the next step without further purification.

[1019] Step 2: (3,3-dimethoxycyclobutyl)methanol

[1020] To the solution of methyl 3, 3 -dimethoxy cyclobutane-1 -carboxylate (5 g, 28.7 mmol) in THF (100 mL) was added LAH (2.4 M in THF, 12.5 mL, 30 mmol,) at 0 °C. The reaction mixture was warmed to rt and stirred for 2h. The reaction was quenched by addition of water dropwise at 0 °C. The resulting suspension was filtered through a Celite pad, and the solution was extracted with EtOAc, the combined organic layers were washed with sat. NaCl, then dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was used directly in the next step without further purification.

[1021] Step 3: 3-(((tert-butyldimethylsilyl)oxy)methyl)cyclobutan-l-one 54057 -0028 WO 1 / SNV0021-W01 PATENT

[1022] To the solution of (3,3-dimethoxycyclobutyl)methanol (2.3 g, 15.8 mmol) in acetone (50 mL) and water (25 mL) was added PTSA (2.7 g, 15.8 mmol). The reaction solution was stirred at 70 °C for 2h. After cooled to rt, the reaction was concentrated under vacuum. The residue was diluted with EtOAc and washed with sat. NaHCOs and sat. NaCl, then dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was dissolved in DCM (50 mL), TBSC1 (2.5 g, 17 mmol) and imidazole (1.2 g, 17 mmol). The reaction was quenched after 2h. The reaction was diluted with DCM and washed with sat. NaHCOs and sat. NaCl, then dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified using flash column chromatography (EA / Hex, 0 to 30%) to afford the desired product.

[1023] To the solution of 5 -bromo-2 -iodo-pyrimidine (0.7 g, 2.5 mmol) in DCM (20 mL) at - 78 °C was added 2..5 M n-butyllithium in hexanes (1.3 mL, 3.2 mmol) dropwise, after 30 min, a solution of 3-(((tert-butyldimethylsilyl)oxy)methyl)cyclobutan-l-one (0.53 g, 2.5 mmol) in DCM (5 mL) was added dropwise at -78 °C. After 1 h, the reaction was quenched with sat. NH4CI solution. The resulting mixture slowly warmed up to rt. The mixture was diluted with ethyl acetate (50 mL *2), combined organic layer was washed with brine, dried through sodium sulfate. The crude was purified by LCC, eluting from 0-50% EA / Hexanes to give desired product was yellow oil. LCMS calculated for CisfLeBr^CLSi (M+H)+m / z = 373.1; found 373.1.

[1024] Step 5: l-(5-bromopyrimidin-2-yl)-3-(((tert-butyldimethylsilyl)oxy)methyl)cyclobutyl acetate

[1025] 1 -(5 -bromopyrimidin-2-yl)-3 -(((tert-butyldimethylsilyl)oxy)methyl)cyclobutan- 1 -ol (300 mg, 0.81 mmol) in DCM (20 mL) was added AC2O (163 mg, 1.6 mmol), DIEA (0.29 mL, 1.6 mmol) and DMAP (24 mg, 0.2 mmol). The reaction was stirred at rt for 2h then diluted with DCM and washed with sat. NaHCOs and sat. NaCl, then dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was 54057 -0028 WO 1 / SNV0021-W01 PATENT purified using flash column chromatography (EA / Hex, 0 to 30%), the desired peak was collected as desired product. LCMS calculated for Ci7H2sBrN2O3Si (M+H)+m / z = 415.1; found 415.1.

[1026] Intermediate 12. l-(5-Bromopyrimidin-2-yl)-3-(((tert-butyldimethylsilyl)oxy)methyl)-3- methylcyclobutyl acetate

[1027] Step 1: methyl 3, 3-dimethoxy-l -methylcyclobutane- 1 -carboxylate

[1028] To the solution of methyl 3, 3 -dimethoxy cyclobutane-1 -carboxylate (Intermediate 11, step 1) (20 g, 115 mmol) in THF (400 mL) at -78 °C was added 2 M LDA in THF (115 mL, 230 mmol) dropwise while stirring, after 30 min, Mel (14.3 mL, 230 mmol) was added dropwise at -78 °C. After 1 h, the reaction was quenched with sat. NH4CI solution. The resulting mixture slowly warmed up to rt. The mixture was diluted with ethyl acetate (200 mL *2), combined organic layer was washed with brine, dried through sodium sulfate. The crude was purified with FCC, eluting from 0-30% EA / Hexanes to give desired product as a colorless oil.

[1029] Step 2 to 5: l-(5-bromopyrimidin-2-yl)-3-(((tert-butyldimethylsilyl)oxy)methyl)-3- methylcyclobutyl acetate

[1030] The title compound was prepared using a similar procedure as described for Intermediate 11, with methyl 3,3-dimethoxy-l-methylcyclobutane-l-carboxylate replacing methyl 3,3-dimethoxycyclobutane-l-carboxylate in step 2. The final product was purified using flash column chromatography (EA / Hex, 0 to 30%), the desired peak was collected as the desired product. LCMS calculated for CisH3oBrN203Si (M+H)+m / z = 429.1; found 429.1.

[1031] Intermediate 13. 3-Acetoxy-3-(5-bromopyrimidin-2-yl)cyclobutyl pivalate 54057 -0028 WO 1 / SNV0021-W01 PATENT

[1032] The title compound was prepared using a similar procedure as described for Intermediate 11, with 3 -oxocyclobutyl pivalate replacing 3-(((tert- butyldimethylsilyl)oxy)methyl)cyclobutan-l-one in step 4. The final product was purified using flash column chromatography (EA / Hex, 0 to 30%), the desired peak was collected as the desired product. LCMS calculated for CisftoB...

Claims

1. 54057 -0028 WO 1 / SNV0021-W01 PATENTWHAT IS CLAIMED IS:

1. A compound of Formula I:or a pharmaceutically acceptable salt thereof, wherein: m is 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, 4, 5, or 6; q is 0, 1, 2, 3, or, 4; r is 0, 1, 2, 3, or, 4; t is 0, 1, 2, 3, or, 4; provided that the sum of r and t is not 0;Z1is N or CR3;Z2is N or CR4;X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;Y1is N or CR5;Y2is N or CR6;Y3is N or CR7;Ring A is C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl;Ring B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from Ci-e alkylene, C2-6 alkenylene, C3-10 cycloalkylene, 4-10 membered heterocycloalkylene, phenylene, 5-10 membered heteroarylene, -O-, -S-, -N(RL2c)-, -C(O)-, -S(O)-, -S(O)2-, and -S(O)(=NRL2e)-, wherein the C1-6 alkylene, C2-6 alkenylene, C3-10 cycloalkylene, 4-10 membered heterocycloalkylene, phenylene, and 5-10 membered heteroarylene of L1, L2, L3, and L4are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; each RL2cis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, CA e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered54057 -0028 WO 1 / SNV0021-W01 PATENT heterocycloalkyl) -Ci .4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORaL2, -NRcL2RdL2, -C(O)RaL2, -C(O)ORaL2, -C(O)NRcL2RdL2, -C(O)NRcL2(ORaL2), -S(O)RbL2, -S(O)2RbL2, - S(O)NRcL2RdL2, -S(O)2NRcL2RdL2, -S(O)(=NReL2)RbL2, -S(O)(=NReL2)NRcL2RdL2, - C(O)NRcL2S(O)2RbL2, -C(O)NRcL2S(O)2NRcL2RdL2, and -S(O)2NRcL2C(O)RbL2, wherein the Ci. e alkyl, C2-6 alkenyl, C2.e alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RL2care each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; each RL2eis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RL2is independently selected from H, oxo, halo, Ci-e alkyl, C2.e alkenyl, C2.e alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -Ci -4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORaL2, -SRaL2, -NReL2RdL2_N02-C(O)RaL2, -C(O)ORaL2, -C(O)NRcL2RdL2, -C(O)NRcL2(ORaL2), -OC(O)RaL2, -OC(O)NRcL2RdL2, -OC(O)ORaL2, -OS(O)2RbL2, -OS(O)2NRcL2RdL2, -NRcL2C(O)RaL2, - NRcL2C(O)ORaL2, -NRcL2C(O)NRcL2RdL2, -NRcL2S(O)2RbL2, -NRcL2S(O)2NRcL2RdL2, - NRcL2ORaL2, -NRcL2S(O)RbL2, -NRcL2S(O)NRcL2RdL2, -S(O)RbL2, -S(O)2RbL2, -S(O)NRcL2RdL2, -S(O)2NRcL2RdL2, -C(=NReL2)RaL2, -C(=NReL2)NRcL2RdL2, -NRcL2C(=NReL2)RaL2, - NRcL2C(=NReL2)NRcL2RdL2, -NRcL2S(O)(=NReL2)RbL2, -NRcL2S(O)(=NReL2)NRcL2RdL2, - OS(O)(=NReL2)RbL2, -S(O)(=NReL2)RbL2, -S(O)(=NReL2)NRcL2RdL2, -C(O)NRcL2S(O)2RbL2, - C(O)NRcL2S(O)2NRcL2RdL2, -S(O)2NRcL2C(O)RbL2, -NRcL2S(O)NRcL2C(O)RbL2, and - P(O)RfL2RgL2, wherein the Ci-e alkyl, C2.e alkenyl, C2.e alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci-4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of RL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RaL2, RcL2, and RdL2is independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2.e alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -Ci -4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.e alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered54057 -0028 WO 1 / SNV0021-W01 PATENT heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of RaL2, RcL2, and RdL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any RcL2and RdL2attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RbL2is independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl of RbL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each ReL2is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; each RlL2and RgL2are independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; each R1is independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-14 cycloalkyl-Ci.4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-14 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORal, -SRal, - NRclRdl, -NO2, -C(O)Ral, -C(O)ORal, -C(O)NRclRdl, -C(O)NRcl(ORal), -OC(O)Ral, - OC(O)NRclRdl, -OC(O)ORal, -OS(O)2Rbl, -OS(O)2NRclRdl, -NRclC(O)Ral, -NRclC(O)ORal, - NRclC(O)NRclRdl, -NRclS(O)2Rbl, -NRclS(O)2NRclRdl, -NRcl0Ral, -NRclS(O)Rbl, - NRclS(O)NRclRdl, -S(O)Rbl, -S(O)2Rbl, -S(O)NRclRdl, -S(O)2NRclRdl, -C(=NRel)Ral, - C(=NRel)NRclRdl, -NRclC(=NRel)Ral, -NRclC(=NRel)NRclRdl, -NRclS(O)(=NRel)Rbl, - NRclS(O)(=NRel)NRclRdl, -OS(O)(=NRel)Rbl, -S(O)(=NRel)Rbl, -S(O)(=NRel)NRclRdl, - C(O)NRclS(O)2Rbl, -C(O)NRclS(O)2NRclRdl, -S(O)2NRclC(O)Rbl, -NRclS(O)NRclC(O)Rbl, and -P(O)RflRgl, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-1454057 -0028 WO 1 / SNV0021-W01 PATENT cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-14 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-14 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, two R1, together with the atoms to which they are attached to, form a C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, or 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ral, Rcl, and Rdlare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, any Rcland Rdlattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Rblis independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rblare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Relis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;54057 -0028 WO 1 / SNV0021-W01 PATENT each Rfland Rglare independently selected from H, Ci-e alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R1Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, -SRalA, -NReiARdiA _NO2-C(O)RalA, -C(O)ORalA, -C(O)NRclARdlA, -C(O)NRclA(ORalA), - OC(O)RalA, -OC(O)NRclARdlA, -OC(O)ORalA, -OS(O)2RblA, -OS(O)2NRclARdlA, - NRclAC(O)RalA, -NRclAC(O)ORalA, -NRclAC(O)NRclARdlA, -NRclAS(O)2RblA, - NRclAS(O)2NRclARdlA, -NRclAORalA, -NRclAS(O)RblA, -NRclAS(O)NRclARdlA, -S(O)RblA, - S(O)2RblA, -S(O)NRclARdlA, -S(O)2NRclARdlA, -C(=NRelA)RalA, -C(=NRelA)NRclARdlA, - NRclAC(=NRelA)RalA, -NRclAC(=NRelA)NRclARdlA, -NRclAS(O)(=NRelA)RblA, - NRclAS(O)(=NRelA)NRclARdlA, -OS(O)(=NRelA)RblA, -S(O)(=NRelA)RblA, - S(O)(=NRelA)NRclARdlA, -C(O)NRclAS(O)2RblA, -C(O)NRclAS(O)2NRclARdlA, - S(O)2NRclAC(O)RblA, -NRclAS(O)NRclAC(O)RblA, and -P(O)RflARglA, wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RalA, RclA, and RdlAare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Bsubstituents; or, any RclAand RdlAattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Bsubstituents;54057 -0028 WO 1 / SNV0021-W01 PATENT each RblAis independently selected from Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RblAare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Bsubstituents; each RelAis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RflAand RglAare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R1Bis independently selected from oxo, H, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalB, -SRalB, -NReiBRdiB _NO2-C(O)RalB, -C(O)ORalB, -C(O)NRclBRdlB, -C(O)NRclB(ORalB), -OC(O)RalB, -OC(O)NRclBRdlB, -OC(O)ORalB, -OS(O)2RblB, -OS(O)2NRclBRdlB, -NRclBC(O)RalB, - NRclBC(O)ORalB, -NRclBC(O)NRclBRdlB, -NRclBS(O)2RblB, -NRclBS(O)2NRclBRdlB, - NRclBORalB, -NRclBS(O)RblB, -NRclBS(O)NRclBRdlB, -S(O)RblB, -S(O)2RblB, -S(O)NRclBRdlB, -S(O)2NRclBRdlB, -C(=NRelB)RalB, -C(=NRelB)NRclBRdlB, -NRclBC(=NRelB)RalB, - NRclBC(=NRelB)NRclBRdlB, -NRclBS(O)(=NRelB)RblB, -NRclBS(O)(=NRelB)NRclBRdlB, - OS(O)(=NRelB)RblB, -S(O)(=NRelB)RblB, -S(O)(=NRelB)NRclBRdlB, -C(O)NRclBS(O)2RblB, - C(O)NRclBS(O)2NRclBRdlB, -S(O)2NRclBC(O)RblB, -NRclBS(O)NRclBC(O)RblB, and - P(O)RflBRglB, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R1Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;54057 -0028 WO 1 / SNV0021-W01 PATENT each RalB, RclB, and RdlBis independently selected from H, Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RalB, RclB, and RdlBare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any RclBand RdlBattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RblBis independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RblBare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RelBis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RflBand RglBare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;R20is selected from C2-6 alkenyl, C2-6 alkynyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C2-6 alkenyl, C2-6 alkynyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered54057 -0028 WO 1 / SNV0021-W01 PATENT heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents; each R2is independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, -SRa2, - NRc2Rd2, -NO2, -C(O)Ra2, -C(O)ORa2, -C(O)NRc2Rd2, -C(O)NRc2(ORa2), -OC(O)Ra2, - OC(O)NRc2Rd2, -OC(O)ORa2, -OS(O)2Rb2, -OS(O)2NRc2Rd2, -NRc2C(O)Ra2, -NRc2C(O)ORa2, - NRc2C(O)NRc2Rd2, -NRc2S(O)2Rb2, -NRc2S(O)2NRc2Rd2, -NRc2ORa2, -NRc2S(O)Rb2, - NRc2S(O)NRc2Rd2, -S(O)Rb2, -S(O)2Rb2, -S(O)NRc2Rd2, -S(O)2NRc2Rd2, -C(=NRe2)Ra2, - C(=NRe2)NRc2Rd2, -NRc2C(=NRe2)Ra2, -NRc2C(=NRe2)NRc2Rd2, -NRc2S(O)(=NRe2)Rb2, - NRc2S(O)(=NRe2)NRc2Rd2, -OS(O)(=NRe2)Rb2, -S(O)(=NRe2)Rb2, -S(O)(=NRe2)NRc2Rd2, - C(O)NRc2S(O)2Rb2, -C(O)NRc2S(O)2NRc2Rd2, -S(O)2NRc2C(O)Rb2, -NRc2S(O)NRc2C(O)Rb2, and -P(O)Rf2Rg2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra2, Rc2, and Rd2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; or, any Rc2and Rd2attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Rb2is independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered54057 -0028 WO 1 / SNV0021-W01 PATENT heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Re2is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RQand Rg2are independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R2Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2A, -SRa2A, -NRC2ARd2A _N02-C(O)Ra2A, -C(O)ORa2A, -C(O)NRc2ARd2A, -C(O)NRc2A(ORa2A), - OC(O)Ra2A, -OC(O)NRc2ARd2A, -OC(O)ORa2A, -OS(O)2Rb2A, -OS(O)2NRc2ARd2A, - NRc2AC(O)Ra2A, -NRc2AC(O)ORa2A, -NRc2AC(O)NRc2ARd2A, -NRc2AS(O)2Rb2A, - NRc2AS(O)2NRc2ARd2A, -NRc2AORa2A, -NRc2AS(O)Rb2A, -NRc2AS(O)NRc2ARd2A, -S(O)Rb2A, - S(O)2Rb2A, -S(O)NRc2ARd2A, -S(O)2NRc2ARd2A, -C(=NRe2A)Ra2A, -C(=NRe2A)NRc2ARd2A, - NRc2AC(=NRe2A)Ra2A, -NRc2AC(=NRe2A)NRc2ARd2A, -NRc2AS(O)(=NRe2A)Rb2A, - NRc2AS(O)(=NRe2A)NRc2ARd2A, -OS(O)(=NRe2A)Rb2A, -S(O)(=NRe2A)Rb2A, - S(O)(=NRe2A)NRc2ARd2A, -C(O)NRc2AS(O)2Rb2A, -C(O)NRc2AS(O)2NRc2ARd2A, - S(O)2NRc2AC(O)Rb2A, -NRc2AS(O)NRc2AC(O)Rb2A, and -P(O)R£2ARg2A, wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Bsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-654057 -0028 WO 1 / SNV0021-W01 PATENT alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra2A, Rc2A, and Rd2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Bsubstituents; or, any Rc2Aand Rd2Aattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Bsubstituents; each Rb2Ais independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Bsubstituents; each Re2Ais independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RQAand Rg2Aare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R2Bis independently selected from oxo, H, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2B, -SRa2B, -NRC2BRd2B _N02-C(O)Ra2B, -C(O)ORa2B, -C(O)NRc2BRd2B, -C(O)NRc2B(ORa2B), -OC(O)Ra2B, -OC(O)NRc2BRd2B, -OC(O)ORa2B, -OS(O)2Rb2B, -OS(O)2NRc2BRd2B, -NRc2BC(O)Ra2B, - NRc2BC(O)ORa2B, -NRc2BC(O)NRc2BRd2B, -NRc2BS(O)2Rb2B, -NRc2BS(O)2NRc2BRd2B, - NRc2BORa2B, -NRc2BS(O)Rb2B, -NRc2BS(O)NRc2BRd2B, -S(O)Rb2B, -S(O)2Rb2B, -S(O)NRc2BRd2B,54057 -0028 WO 1 / SNV0021-W01 PATENT-S(O)2NRc2BRd2B, -C(=NRe2B)Ra2B, -C(=NRe2B)NRc2BRd2B, -NRc2BC(=NRe2B)Ra2B, - NRc2BC(=NRe2B)NRc2BRd2B, -NRc2BS(O)(=NRe2B)Rb2B, -NRc2BS(O)(=NRe2B)NRc2BRd2B, - OS(O)(=NRe2B)Rb2B, -S(O)(=NRe2B)Rb2B, -S(O)(=NRe2B)NRc2BRd2B, -C(O)NRc2BS(O)2Rb2B, - C(O)NRc2BS(O)2NRc2BRd2B, -S(O)2NRc2BC(O)Rb2B, -NRc2BS(O)NRc2BC(O)Rb2B, and - P(O)Rf2BRg2B, wherein the Ci-e alkyl, C2.e alkenyl, C2.e alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R2Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Ra2B, Rc2B, and Rd2Bis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra2B, Rc2B, and Rd2Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any Rc2Band Rd2Battached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Rb2Bis independently selected from Ci-e alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb2Bare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Re2Bis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2.e alkenyl, C2.e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;54057 -0028 WO 1 / SNV0021-W01 PATENT each RQBand Rg2Bare independently selected from H, Ci-e alkyl, Ci-6 alkoxy, Ci-6 haloalkyl, Ci-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;R3and R4are independently selected from H, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa3, -SRa3, - NRc3Rd3, -NO2, -C(O)Ra3, -C(O)ORa3, -C(O)NRc3Rd3, -C(O)NRc3(ORa3), -OC(O)Ra3, - OC(O)NRc3Rd3, -OC(O)ORa3, -OS(O)2Rb3, -OS(O)2NRc3Rd3, -NRc3C(O)Ra3, -NRc3C(O)ORa3, - NRc3C(O)NRc3Rd3, -NRc3S(O)2Rb3, -NRc3S(O)2NRc3Rd3, -NRc3ORa3, -NRc3S(O)Rb3, - NRc3S(O)NRc3Rd3, -S(O)Rb3, -S(O)2Rb3, -S(O)NRc3Rd3, -S(O)2NRc3Rd3, -C(=NRe3)Ra3, - C(=NRe3)NRc3Rd3, -NRc3C(=NRe3)Ra3, -NRc3C(=NRe3)NRc3Rd3, -NRc3S(O)(=NRe3)Rb3, - NRc3S(O)(=NRe3)NRc3Rd3, -OS(O)(=NRe3)Rb3, -S(O)(=NRe3)Rb3, -S(O)(=NRe3)NRc3Rd3, - C(O)NRc3S(O)2Rb3, -C(O)NRc3S(O)2NRc3Rd3, -S(O)2NRc3C(O)Rb3, -NRc3S(O)NRc3C(O)Rb3, and -P(O)Rf3Rg3, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R3and R4are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, R3and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, R3and one of L1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, R4and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, R4and one of L2, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-1054057 -0028 WO 1 / SNV0021-W01 PATENT membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Ra3, Rc3, and Rd3is independently selected from H, Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -Ci -4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of Ra3, Rc3, and Rd3are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any Rc3and Rd3attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Rb3is independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl of Rb3are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Re3is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; each R° and Rg3are independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl;R5is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl;R6is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl;R7is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl; and54057 -0028 WO 1 / SNV0021-W01 PATENT each RGis independently selected from H, OH, CN, halo, oxo, Ci-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl, aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino; provided that when t is 0, Z1is CR3, Z2is CR4, and (L3)ris -CH2-, then:(i) R3and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or(ii) R3and one of L1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or(iii) R4and one of R1, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or(iv) R4and one of L2, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: m is 0, 1, 2, 3, 4, 5, or 6; p is 0, 1, 2, 3, 4, 5, or 6; q is 0, 1, 2, 3, or, 4; r is 0, 1, 2, 3, or, 4; t is 0, 1, 2, 3, or, 4; provided that the sum of r and t is not 0;Z1is N or CR3;Z2is N or CR4;54057 -0028 WO 1 / SNV0021-W01 PATENTX1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;Y1is N or CR5;Y2is N or CR6;Y3is N or CR7;Ring A is C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, or 5-10 membered heteroaryl;Ring B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from Ci-e alkylene, C2-6 alkenylene, C3-10 cycloalkylene, 4-10 membered heterocycloalkylene, phenylene, 5-10 membered heteroarylene, -O-, -S-, -N(RL2c)-, -C(O)-, -S(O)-, -S(O)2-, and -S(O)(=NRL2e)-, wherein the C1-6 alkylene, C2-6 alkenylene, C3-10 cycloalkylene, 4-10 membered heterocycloalkylene, phenylene, and 5-10 membered heteroarylene of L1, L2, L3, and L4are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; each RL2cis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, CA e alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORaL2, -NRcL2RdL2, -C(O)RaL2, -C(O)ORaL2, -C(O)NRcL2RdL2, -C(O)NRcL2(ORaL2), -S(O)RbL2, -S(O)2RbL2, - S(O)NRcL2RdL2, -S(O)2NRcL2RdL2, -S(O)(=NReL2)RbL2, -S(O)(=NReL2)NRcL2RdL2, - C(O)NRcL2S(O)2RbL2, -C(O)NRcL2S(O)2NRcL2RdL2, and -S(O)2NRcL2C(O)RbL2, wherein the Ci. e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RL2care each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; each RL2eis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RL2is independently selected from H, oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORaL2, -SRaL2, -NRCL2RdL2 _n02-C(O)Rab2, -C(O)ORaL2, -C(O)NRcL2RdL2, -C(O)NRcL2(ORaL2), -OC(O)RaL2,54057 -0028 WO 1 / SNV0021-W01 PATENT-OC(O)NRcL2RdL2, -OC(O)ORaL2, -OS(O)2RbL2, -OS(O)2NRcL2RdL2, -NRcL2C(O)RaL2, - NRcL2C(O)ORaL2, -NRcL2C(O)NRcL2RdL2, -NRcL2S(O)2RbL2, -NRcL2S(O)2NRcL2RdL2, - NRcL2ORaL2, -NRcL2S(O)RbL2, -NRcL2S(O)NRcL2RdL2, -S(O)RbL2, -S(O)2RbL2, -S(O)NRcL2RdL2, -S(O)2NRcL2RdL2, -C(=NReL2)RaL2, -C(=NReL2)NRcL2RdL2, -NRcL2C(=NReL2)RaL2, - NRcL2C(=NReL2)NRcL2RdL2, -NRcL2S(O)(=NReL2)RbL2, -NRcL2S(O)(=NReL2)NRcL2RdL2, - OS(O)(=NReL2)RbL2, -S(O)(=NReL2)RbL2, -S(O)(=NReL2)NRcL2RdL2, -C(O)NRcL2S(O)2RbL2, - C(O)NRcL2S(O)2NRcL2RdL2, -S(O)2NRcL2C(O)RbL2, -NRcL2S(O)NRcL2C(O)RbL2, and - P(O)RfL2RgL2, wherein the Ci-e alkyl, C2.e alkenyl, C2.e alkynyl, Ci-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci-4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of RL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RaL2, RcL2, and RdL2is independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2.e alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -Ci -4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2.e alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of RaL2, RcL2, and RdL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any RcL2and RdL2attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RbL2is independently selected from Ci-e alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl of RbL2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each ReL2is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2.e alkenyl, C2.e alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered54057 -0028 WO 1 / SNV0021-W01 PATENT heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; each RlL2and RgL2are independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; each R1is independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORal, -SRal, - NRclRdl, -NO2, -C(O)Ral, -C(O)ORal, -C(O)NRclRdl, -C(O)NRcl(ORal), -OC(O)Ral, - OC(O)NRclRdl, -OC(O)ORal, -OS(O)2Rbl, -OS(O)2NRclRdl, -NRclC(O)Ral, -NRclC(O)ORal, - NRclC(O)NRclRdl, -NRclS(O)2Rbl, -NRclS(O)2NRclRdl, -NRclORal, -NRclS(O)Rbl, - NRclS(O)NRclRdl, -S(O)Rbl, -S(O)2Rbl, -S(O)NRclRdl, -S(O)2NRclRdl, -C(=NRel)Ral, - C(=NRel)NRclRdl, -NRclC(=NRel)Ral, -NRclC(=NRel)NRclRdl, -NRclS(O)(=NRel)Rbl, - NRclS(O)(=NRel)NRclRdl, -OS(O)(=NRel)Rbl, -S(O)(=NRel)Rbl, -S(O)(=NRel)NRclRdl, - C(O)NRclS(O)2Rbl, -C(O)NRclS(O)2NRclRdl, -S(O)2NRclC(O)Rbl, -NRclS(O)NRclC(O)Rbl, and -P(O)RflRgl, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, two R1, together with the atoms to which they are attached to, form a C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, or 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ral, Rcl, and Rdlare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents;54057 -0028 WO 1 / SNV0021-W01 PATENT or, any Rcland Rdlatached to the same N atom, together with the N atom to which they are atached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Rblis independently selected from Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rblare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Relis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each Rfland Rglare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R1Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, -SRalA, -NReiARdiA _NO2-C(O)RalA, -C(O)ORalA, -C(O)NRclARdlA, -C(O)NRclA(ORalA), - OC(O)RalA, -OC(O)NRclARdlA, -OC(O)ORalA, -OS(O)2RblA, -OS(O)2NRclARdlA, - NRclAC(O)RalA, -NRclAC(O)ORalA, -NRclAC(O)NRclARdlA, -NRclAS(O)2RblA, - NRclAS(O)2NRclARdlA, -NRclAORalA, -NRclAS(O)RblA, -NRclAS(O)NRclARdlA, -S(O)RblA, - S(O)2RblA, -S(O)NRclARdlA, -S(O)2NRclARdlA, -C(=NRelA)RalA, -C(=NRelA)NRclARdlA, - NRclAC(=NRelA)RalA, -NRclAC(=NRelA)NRclARdlA, -NRclAS(O)(=NRelA)RblA, - NRclAS(O)(=NRelA)NRclARdlA, -OS(O)(=NRelA)RblA, -S(O)(=NRelA)RblA, - S(O)(=NRelA)NRclARdlA, -C(O)NRclAS(O)2RblA, -C(O)NRclAS(O)2NRclARdlA, - S(O)2NRclAC(O)RblA, -NRclAS(O)NRclAC(O)RblA, and -P(O)RflARglA, wherein the Ci-6alkyl,54057 -0028 WO 1 / SNV0021-W01 PATENTC2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RalA, RclA, and RdlAare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any RclAand RdlAattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RblAis independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of RblAare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each RelAis independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RflAand RglAare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-54057 -0028 WO 1 / SNV0021-W01 PATENTCi-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;R20is selected from C2-6 alkenyl, C2-6 alkynyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C2-6 alkenyl, C2-6 alkynyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents; each R2is independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, -SRa2, - NRc2Rd2, -NO2, -C(O)Ra2, -C(O)ORa2, -C(O)NRc2Rd2, -C(O)NRc2(ORa2), -OC(O)Ra2, - OC(O)NRc2Rd2, -OC(O)ORa2, -OS(O)2Rb2, -OS(O)2NRc2Rd2, -NRc2C(O)Ra2, -NRc2C(O)ORa2, - NRc2C(O)NRc2Rd2, -NRc2S(O)2Rb2, -NRc2S(O)2NRc2Rd2, -NRc2ORa2, -NRc2S(O)Rb2, - NRc2S(O)NRc2Rd2, -S(O)Rb2, -S(O)2Rb2, -S(O)NRc2Rd2, -S(O)2NRc2Rd2, -C(=NRe2)Ra2, - C(=NRe2)NRc2Rd2, -NRc2C(=NRe2)Ra2, -NRc2C(=NRe2)NRc2Rd2, -NRc2S(O)(=NRe2)Rb2, - NRc2S(O)(=NRe2)NRc2Rd2, -OS(O)(=NRe2)Rb2, -S(O)(=NRe2)Rb2, -S(O)(=NRe2)NRc2Rd2, - C(O)NRc2S(O)2Rb2, -C(O)NRc2S(O)2NRc2Rd2, -S(O)2NRc2C(O)Rb2, -NRc2S(O)NRc2C(O)Rb2, and -P(O)Rf2Rg2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl) -C 1-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra2, Rc2, and Rd2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; or, any Rc2and Rd2attached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents;54057 -0028 WO 1 / SNV0021-W01 PATENT each Rb2is independently selected from Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Re2is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RQand Rg2are independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each R2Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2A, -SRa2A, -NRC2ARd2A _n02-C(O)Ra2A, -C(O)ORa2A, -C(O)NRc2ARd2A, -C(O)NRc2A(ORa2A), - OC(O)Ra2A, -OC(O)NRc2ARd2A, -OC(O)ORa2A, -OS(O)2Rb2A, -OS(O)2NRc2ARd2A, - NRc2AC(O)Ra2A, -NRc2AC(O)ORa2A, -NRc2AC(O)NRc2ARd2A, -NRc2AS(O)2Rb2A, - NRc2AS(O)2NRc2ARd2A, -NRc2AORa2A, -NRc2AS(O)Rb2A, -NRc2AS(O)NRc2ARd2A, -S(O)Rb2A, - S(O)2Rb2A, -S(O)NRc2ARd2A, -S(O)2NRc2ARd2A, -C(=NRe2A)Ra2A, -C(=NRe2A)NRc2ARd2A, - NRc2AC(=NRe2A)Ra2A, -NRc2AC(=NRe2A)NRc2ARd2A, -NRc2AS(O)(=NRe2A)Rb2A, - NRc2AS(O)(=NRe2A)NRc2ARd2A, -OS(O)(=NRe2A)Rb2A, -S(O)(=NRe2A)Rb2A, - S(O)(=NRe2A)NRc2ARd2A, -C(O)NRc2AS(O)2Rb2A, -C(O)NRc2AS(O)2NRc2ARd2A, - S(O)2NRc2AC(O)Rb2A, -NRc2AS(O)NRc2AC(O)Rb2A, and -P(O)R£2ARg2A, wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of54057 -0028 WO 1 / SNV0021-W01 PATENTR2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H, Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Ra2A, Rc2A, and Rd2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any Rc2Aand Rd2Aattached to the same N atom, together with the N atom to which they are attached, form a 4-10 membered heterocycloalkyl group, wherein the 4-10 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Rb2Ais independently selected from Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of Rb2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Re2Ais independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl; each RQAand Rg2Aare independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl- C1-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl;R3and R4are independently selected from H, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-654057 -0028 WO 1 / SNV0021-W01 PATENT membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa3, -SRa3, - NRc3Rd3, -NO2, -C(O)Ra3, -C(O)ORa3, -C(O)NRc3Rd3, -C(O)NRc3(ORa3), -OC(O)Ra3, - OC(O)NRc3Rd3, -OC(O)ORa3, -OS(O)2Rb3, -OS(O)2NRc3Rd3, -NRc3C(O)Ra3, -NRc3C(O)ORa3, - NRc3C(O)NRc3Rd3, -NRc3S(O)2Rb3, -NRc3S(O)2NRc3Rd3, -NRc3ORa3, -NRc3S(O)Rb3, - NRc3S(O)NRc3Rd3, -S(O)Rb3, -S(O)2Rb3, -S(O)NRc3Rd3, -S(O)2NRc3Rd3, -C(=NRe3)Ra3, - C(=NRe3)NRc3Rd3, -NRc3C(=NRe3)Ra3, -NRc3C(=NRe3)NRc3Rd3, -NRc3S(O)(=NRe3)Rb3, - NRc3S(O)(=NRe3)NRc3Rd3, -OS(O)(=NRe3)Rb3, -S(O)(=NRe3)Rb3, -S(O)(=NRe3)NRc3Rd3, - C(O)NRc3S(O)2Rb3, -C(O)NRc3S(O)2NRc3Rd3, -S(O)2NRc3C(O)Rb3, -NRc3S(O)NRc3C(O)Rb3, and -P(O)Rf3Rg3, wherein the Ci-e alkyl, C2.e alkenyl, C2.e alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R3and R4are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, R3and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, R3and one of L1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, R4and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or, R4and one of L2, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Ra3, Rc3, and Rd3is independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2.e alkenyl, C2.e alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl, wherein the C1-6 alkyl, C2.e alkenyl, C2.e alkynyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered54057 -0028 WO 1 / SNV0021-W01 PATENT heterocycloalkyl) -Ci .4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of Ra3, Rc3, and Rd3are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; or, any Rc3and Rd3attached to the same N atom, together with the N atom to which they are attached, form a 4-7 membered heterocycloalkyl group, wherein the 4-7 membered heterocycloalkyl group is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Rb3is independently selected from Ci-e alkyl, Ci-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl, wherein the C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci-4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl)-Ci-4 alkyl, and (5-6 membered heteroaryl) -C 1-4 alkyl of Rb3are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Re3is independently selected from H, OH, CN, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl; each R° and Rg3are independently selected from H, Ci-e alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, C3-7 cycloalkyl-Ci.4 alkyl, phenyl-Ci.4 alkyl, (4-7 membered heterocycloalkyl) -C 1-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl;R5is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl;R6is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl;R7is selected from H, halo, -CN, Ci-e alkyl, C1-6 haloalkyl, Ci-e alkoxyl, and C1-6 haloalkoxyl; and each RGis independently selected from H, OH, CN, halo, oxo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, amino, C1-3 alkylamino, di(Ci-3 alkyl)amino, thio, C1-3 alkylthio, C1-3 alkylsulfinyl, C1-3 alkylsulfonyl, carbamyl, C1-3 alkylcarbamyl, di(Ci-3 alkyl)carbamyl, carboxy, C1-3 alkylcarbonyl, C1-3 alkoxycarbonyl, C1-3 alkylcarbonyloxy, C1-3 alkylcarbonylamino, C1-3 alkoxycarbonylamino, aminocarbonyloxy, C1-3 alkylaminocarbonyloxy, di(Ci-3 alkyl)aminocarbonyloxy, C1-3 alkylsulfonylamino, aminosulfonyl, C1-3 alkylaminosulfonyl, di(Ci-3 alkyl)aminosulfonyl,54057 -0028 WO 1 / SNV0021-W01 PATENT aminosulfonylamino, C1-3 alkylaminosulfonylamino, di(Ci-3 alkyl)aminosulfonylamino, aminocarbonylamino, C1-3 alkylaminocarbonylamino, and di(Ci-3 alkyl)aminocarbonylamino; provided that when t is 0, Z1is CR3, Z2is CR4, and (L3)ris -CH2-, then:(i) R3and one of R1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or(ii) R3and one of L1, together with the atoms to which they are attached to, form a C3- 10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or(iii) R4and one of R1, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; or(iv) R4and one of L2, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein X1is C.

4. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein X2is N.

5. The compound of any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein X3is C.

6. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein X4is C.

7. The compound of any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein Y1is CR5.54057 -0028 WO 1 / SNV0021-W01 PATENT8. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein R5is selected from H and Ci-e alkyl.

9. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein R5is H.

10. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein Y2is CR6.

11. The compound of any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein R6is selected from H, Ci-6 alkyl, and halo.

12. The compound of any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein R6is H or fluoro.

13. The compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein Y3is CR7.

14. The compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein R7is selected from H, Ci-6 alkyl, and halo.

15. The compound of any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein R7is H or fluoro.

16. The compound of any one of claims 1 to 15, or a pharmaceutically acceptable salt thereof, wherein Z1is CR3.

17. The compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein R3is selected from H and Ci-6 alkyl.

18. The compound of any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof, wherein R3is H.

19. The compound of any one of claims 1 to 18, or a pharmaceutically acceptable salt thereof, wherein Z2is CR4.54057 -0028 WO 1 / SNV0021-W01 PATENT20. The compound of any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, wherein R4is selected from H and Ci-6 alkyl.

21. The compound of any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, wherein R4is H.

22. The compound of any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof, wherein Z1is N.

23. The compound of any one of claims 1 to 22, or a pharmaceutically acceptable salt thereof, wherein q is 0.

24. The compound of any one of claims 1 to 23, or a pharmaceutically acceptable salt thereof, wherein r is 1.

25. The compound of any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein each L3is independently selected from Ci-6 alkylene.

26. The compound of any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein each L3is independently selected from C1-3 alkylene.

27. The compound of any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, wherein each L3is -CH2-.

28. The compound of any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof, wherein t is 0 or 1.

29. The compound of any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, wherein each L4is independently selected from C1-6 alkylene.

30. The compound of any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, wherein each L4is independently selected from C1-3 alkylene.

31. The compound of any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof, wherein each L4is -CH2-.54057 -0028 WO 1 / SNV0021-W01 PATENT32. The compound of any one of claims 1 to 31, or a pharmaceutically acceptable salt thereof, wherein p is 1 or 2.

33. The compound of any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, wherein each L2is independently selected from Ci-6 alkylene, -N(RL2c)-, and -C(O)-, wherein the Ci-6 alkylene of L2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RL2substituents; and each RL2cis independently selected from H and Ci-6 alkyl.

34. The compound of any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, wherein each L2is independently selected from C1-3 alkylene, -N(RL2c)-, and -C(O)-; and each RL2cis independently selected from H and C1-3 alkyl.

35. The compound of any one of claims 1 to 32, or a pharmaceutically acceptable salt thereof, wherein each L2is independently selected from -CH2-, -NH-, -N(CH;)-. and -C(O)-.

36. The compound of any one of claims 1 to 19 and 22 to 32, or a pharmaceutically acceptable salt thereof, wherein R4and one of L2, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl, wherein the C3-10 cycloalkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

37. The compound of any one of claims 1 to 19 and 22 to 32, or a pharmaceutically acceptable salt thereof, wherein R4and one of L2, together with the atoms to which they are attached to, form a 4-10 membered heterocycloalkyl, which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents.

38. The compound of any one of claims 1 to 19 and 22 to 32, or a pharmaceutically acceptable salt thereof, wherein R4and one of L2, together with the atoms to which they are attached to, form a 4-7 membered heterocycloalkyl.

39. The compound of any one of claims 1 to 19 and 22 to 32, or a pharmaceutically acceptable salt thereof, wherein R4and one of L2, together with the atoms to which they are attached to, form a pyrrolidine ring.54057 -0028 WO 1 / SNV0021-W01 PATENT40. The compound of any one of claims 1 to 39, or a pharmaceutically acceptable salt thereof, wherein Ring A is C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, or 5-6 membered heteroaryl.

41. The compound of any one of claims 1 to 39, or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl.

42. The compound of any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof, wherein m is 0, 1, 2, or 3.

43. The compound of any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof, wherein m is 1 , 2, or 3.

44. The compound of any one of claims 1 and 3 to 43, or a pharmaceutically acceptable salt thereof, wherein each R1is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; and each Ral, Rcl, and Rdlis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

45. The compound of any one of claims 1 and 3 to 43, or a pharmaceutically acceptable salt thereof, wherein each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, and -ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; and each Ralis independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

46. The compound of any one of claims 1 and 3 to 45, wherein each R1Ais independently selected from oxo, C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-454057 -0028 WO 1 / SNV0021-W01 PATENT alkyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, and C3-7 cycloalkyl-Ci-4 alkyl.

47. The compound of any one of claims 1 and 3 to 46, wherein each R1Bis independently selected from C1-6 alkyl, CN, and -C(O)NRclBRdlB, wherein the C1-6 alkyl of R1Bis optionally substituted with ORalB; and each RalB, RclB, and RdlBis independently selected from H, C1-6 alkyl, and C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with CN.

48. The compound of any one of claims 1 and 3 to 45, wherein each R1Ais independently selected from oxo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from H, C1-6 alkyl, and C3-7 cycloalkyl-Ci.4 alkyl; each R1Bis independently selected from C1-6 alkyl, CN, and -C(O)NRclBRdlB, wherein the C1-6 alkyl of R1Bis optionally substituted with ORalB; and each RalB, RclB, and RdlBis independently selected from H, C1-6 alkyl, and C3-7 cycloalkyl, wherein the C3-7 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with CN.

49. The compound of any one of claims 1 and 3 to 45, wherein each R1Ais independently selected from oxo, methyl, ethyl, difluoromethyl, cyano, hydroxy, methoxy, amino, pyridinylmethyl, cyclopropyl, cyclopropylmethyl, cyclopropylmethylamino, pyridinyl, , and pyrimidinyl, wherein the methyl, ethyl, pyridinylmethyl, cyclopropyl, cyclopropylmethyl, pyridinyl, and pyrimidinyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents; and each R1Bis independently selected from hydroxymethyl, cyano, cyclopropylaminocarbonyl, and (cyanocyclopropyl)aminocarbonyl.

50. The compound of any one of claims 1 and 3 to 43, or a pharmaceutically acceptable salt thereof, wherein each R1is independently selected from fluoro, methyl, cyclopropyl,54057 -0028 WO 1 / SNV0021-W01 PATENT pyrrolidinyl, dihydropyridazinyl, oxazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, [ 1 ,2,4]triazolo [1,5 -a]pyrazinyl, [ 1 ,2,4]triazolo [1,5 -a]pyrimidinyl, 6,7-dihydro-5H- pyrazolo[5,l-b][l,3]oxazinyl, 4,5,6,7-tetrahydropyrazolo[l,5-a]pyrimidinyl, 6,7-dihydro- [ 1 ,2,4]triazolo [1,5 -a]pyrimidin-5 (4H)-onyl, 6,7-dihydropyrazolo [1,5 -a]pyrimidin-5 (4H)-onyl, 6,7-dihydropyrazolo[l,5-a]pyrazin-4(5H)-onyl, and difluoromethoxy, wherein the methyl, cyclopropyl, pyrrolidinyl, dihydropyridazinyl, oxazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, [l,2,4]triazolo[l,5-a]pyrazinyl, [l,2,4]triazolo[l,5-a]pyrimidinyl, 6,7-dihydro-5H- pyrazolo[5,l-b][l,3]oxazinyl, 4,5,6,7-tetrahydropyrazolo[l,5-a]pyrimidinyl, 6,7-dihydro- [ 1 ,2,4]triazolo [1,5 -a]pyrimidin-5 (4H)-onyl, 6,7-dihydropyrazolo [ 1 ,5 -a]pyrimidin-5 (4H)-onyl, and 6,7-dihydropyrazolo[l,5-a]pyrazin-4(5H)-onyl, of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents independently selected from oxo, methyl, ethyl, difluoromethyl, cyano, hydroxy, methoxy, amino, pyridinylmethyl, cyclopropyl, cyclopropylmethyl, (cyanocyclopropyl)methyl, cyclopropylmethylamino, cyanopyridinyl, (hydroxymethyl)pyridinyl, (cyclopropylaminocarbonyl)pyridinyl, (cyanocyclopropylaminocarbonyl)pyridinyl, and (cyclop ropylaminocarbonyl)pyrimidinyl .

51. The compound of any one of claims 1 and 3 to 43, or a pharmaceutically acceptable salt thereof, wherein each R1is independently selected from fluoro, methyl, hydroxymethyl, methoxymethyl, cyclopropyl, cyanopyrrolidinyl, methylpyridazin-3(2H)-onyl, methyloxazolyl, methylimidazolyl, pyrazolyl, methylpyrazolyl, ethylpyrazolyl, (amino)(methyl)pyrazolyl, (difluoromethyl)pyrazolyl, (pyridinylmethyl)pyrazolyl, methyltriazolyl, (amino)(methyl)triazolyl, methyltetrazolyl, difluoromethoxy, (cyclopropylmethyl)tetrazolyl, [ 1 ,2,4]triazolo [ 1 ,5 -a]pyrazinyl, [ 1 ,2,4]triazolo [1,5- a]pyrimidinyl, 6,7-dihydro-5H-pyrazolo[5,l-b][l,3]oxazinyl, 4,5,6,7-tetrahydropyrazolo[l,5- a]pyrimidinyl, 6,7-dihydro-[l,2,4]triazolo[l,5-a]pyrimidin-5(4H)-onyl, 6,7- dihydropyrazolo [ 1 ,5 -a]pyrimidin-5 (4H)-onyl, 5 -methyl-6,7-dihydropyrazolo [ 1 ,5 -a]pyrazin- 4(5H)-onyl, ((cyanocyclopropyl)methyl)pyrazolyl, (cyanopyridinyl)pyrazolyl, ((hydroxymethyl)pyridinyl)pyrazolyl, ((cyclopropylaminocarbonyl)pyrimidinyl)pyrazolyl, ((cyclopropylaminocarbonyl)pyridinyl)(amino)pyrazolyl, (((cyanocyclopropyl)aminocarbonyl)pyridinyl)pyrazolyl, ((cyclopropyhnethyl)amino)(methyl)pyrazolyl, (cyanopyridinyl)triazolyl, ((cyclopropylaminocarbonyl)pyridinyl)triazolyl, (amino)(cyclopropyl)pyrazolyl, and ((cyanocyclopropyl)methyl)tetrazolyl.

52. The compound of any one of claims 1 to 43, or a pharmaceutically acceptable salt thereof, wherein each R1is independently selected from halo, Ci-6 alkyl, C2-6 alkenyl, C2-654057 -0028 WO 1 / SNV0021-W01 PATENT alkynyl, Ci-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; and each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

53. The compound of any one of claims 1 to 43, or a pharmaceutically acceptable salt thereof, wherein each R1is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and -ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; and each Ralis independently selected from H, C1-6 alkyl, and C1-6 haloalkyl.

54. The compound of any one of claims 1 to 45, wherein each R1Ais independently selected from oxo, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl- C1-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl)-Ci-4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA; and each RalA, RclA, and RdlAis independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl.

55. The compound of any one of claims 1 to 45, wherein each R1Ais independently selected from oxo, C1-6 alkyl, C1-6 haloalkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, - ORalA, and -NRclARdlA; and each RalA, RclA, and RdlAis independently selected from H and C1-6 alkyl.

56. The compound of any one of claims 1 to 45, wherein each R1Ais independently selected from oxo, methyl, ethyl, difluoromethyl, cyano, hydroxy, methoxy, amino, and pyridinylmethyl .

57. The compound of any one of claims 1 to 43, or a pharmaceutically acceptable salt thereof, wherein each R1is independently selected from fluoro, methyl, cyclopropyl, pyrrolidinyl, dihydropyridazinyl, oxazolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and difluoromethoxy, wherein the methyl, cyclopropyl, pyrrolidinyl, dihydropyridazinyl,54057 -0028 WO 1 / SNV0021-W01 PATENT oxazolyl, imidazolyl, pyrazolyl, triazolyl, and tetrazolyl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents independently selected from oxo, methyl, ethyl, difluoromethyl, cyano, hydroxy, methoxy, amino, and pyridinylmethyl.

58. The compound of any one of claims 1 to 43, or a pharmaceutically acceptable salt thereof, wherein each R1is independently selected from fluoro, methyl, hydroxymethyl, methoxymethyl, cyclopropyl, cyanopyrrolidinyl, methylpyridazin-3(2H)-onyl, methyloxazolyl, methylimidazolyl, pyrazolyl, methylpyrazolyl, ethylpyrazolyl, (amino)(methyl)pyrazolyl, (difluoromethyl)pyrazolyl, (pyridinylmethyl)pyrazolyl, methyltriazolyl, methyltetrazolyl, and difluoromethoxy.

59. The compound of any one of claims 1 to 58, or a pharmaceutically acceptable salt thereof, wherein R20is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents.

60. The compound of any one of claims 1 to 58, or a pharmaceutically acceptable salt thereof, wherein R20is selected from C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents.

61. The compound of any one of claims 1 to 58, or a pharmaceutically acceptable salt thereof, wherein R20is selected from phenyl and 5-6 membered heteroaryl, wherein the phenyl and 5-6 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents.

62. The compound of any one of claims 1 to 58, or a pharmaceutically acceptable salt thereof, wherein R20is selected from phenyl, pyridinyl, and pyrimidinyl, wherein the phenyl, pyridinyl, and pyrimidinyl are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents.

63. The compound of any one of claims 1 to 62, or a pharmaceutically acceptable salt thereof, wherein each R2is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-1054057 -0028 WO 1 / SNV0021-W01 PATENT membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, and - NRc2Rd2, wherein the Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce- 10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; and each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl.

64. The compound of any one of claims 1 to 62, or a pharmaceutically acceptable salt thereof, wherein each R2is independently selected from halo, C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, (5-6 membered heteroaryl)-Ci-4 alkyl, -ORa2, and -NRc2Rd2, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, or 4 independently selected R2Asubstituents; and each Ra2, Rc2, and Rd2is independently selected from H and C1-6 alkyl.

65. The compound of any one of claims 1 to 62, or a pharmaceutically acceptable salt thereof, wherein each R2is independently selected from fluoro, isopropyl, cyclobutyl, azabicyclo[3.1.0]hexanyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, imidazolidinyl, piperidinyl, pyrazolylethyl, and amino, wherein the isopropyl, cyclobutyl, azabicyclo[3.1.0]hexanyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, imidazolidinyl, piperidinyl, and pyrazolylethyl, are each optionally substituted with 1, 2, 3, or 4 independently selected R2Asubstituents.

66. The compound of any one of claims 1 to 65, or a pharmaceutically acceptable salt thereof, wherein each R2Ais independently selected from oxo, halo, C1-6 alkyl, C2-6 alkenyl, C2.6 alkynyl, Ci-6haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci-6 haloalkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; and each Ra2A, Rc2A, and Rd2Ais independently selected from H, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci-6 haloalkyl.54057 -0028 WO 1 / SNV0021-W01 PATENT67. The compound of any one of claims 1 to 65, or a pharmaceutically acceptable salt thereof, wherein each R2Ais independently selected from oxo, Ci-6 alkyl, CN, -ORa2A, - NRc2ARd2A, and -C(O)NRc2ARd2A, wherein each Ci-6 alkyl of R2Ais optionally substituted with hydroxy; and each Ra2A, Rc2A, and Rd2Ais independently selected from H and Ci-6 alkyl.

68. The compound of any one of claims 1 to 65, or a pharmaceutically acceptable salt thereof, wherein each R2Ais independently selected from oxo, methyl, hydroxymethyl, hydroxy, methoxy, cyano, amino, and -C(O)NH2.

69. The compound of any one of claims 1 to 62, or a pharmaceutically acceptable salt thereof, wherein each R2is independently selected from fluoro, hydroxyisopropyl, aminoisopropyl, dihydroxyisopropyl, (hydroxy)(methoxy)isopropyl, (cyano)(hydroxy)isopropyl, hydroxycyclobutyl, (cyano)(hydroxy)(methyl)cyclobutyl, (hydroxymethyl)cyclobutyl, (aminocarbonyl)cyclobutyl, dihydroxycyclobutyl, (amino)(hydroxy)(methyl)cyclobutyl, (hydroxy)(hydroxymethyl)(methyl)cyclobutyl, (amino)(hydroxymethyl)(methyl)cyclobutyl, aminocyclobutyl, 3-methyl-3- azabicyclo[3.1.0]hexanyl, hydroxyoxetanyl, aminotetrahydrofuranyl, hydroxytetrahydrofuranyl, hydroxytetrahydropyranyl, methylimidazolidine-2,4-dionyl, hydroxypiperidinyl, (methylpyrazolyl)(hydroxy)ethyl, and amino.

70. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: m is 0, 1, 2, or 3; p is 1, 2, 3, 4, or 5; q is 0 or 1; r is 1 or 2; t is 0 or 1; Z1is N or CR3; Z2is N or CR4;X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;Y1is CR5;Y2is CR6; Y3is CR7; Ring A is C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, or 5-6 membered heteroaryl;54057 -0028 WO 1 / SNV0021-W01 PATENTRing B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from Ci-e alkylene, -N(RL2c)-, and -C(O)-; each RL2cis independently selected from H and Ci-e alkyl;R20is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents; each R1is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R1Ais independently selected from oxo, Ci-e alkyl, C1-6 haloalkyl, C3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA, wherein the Ci-e alkyl, C1-6 haloalkyl, C 3-10 cycloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-io cycloalkyl-Ci-4 alkyl; each R1Bis independently selected from Ci-e alkyl, CN, and -C(O)NRclBRdlB, wherein the C1-6 alkyl of R1Bis optionally substituted with ORalB; each RalB, RclB, and RdlBis independently selected from H, Ci-e alkyl, and C3-10 cycloalkyl, wherein the C3-10 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with CN; each R2is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, and - NRc2Rd2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce- 10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered54057 -0028 WO 1 / SNV0021-W01 PATENT heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; each R2Ais independently selected from oxo, halo, Ci-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci-6 haloalkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci-6 haloalkyl;R3is selected from H and Ci-e alkyl;R4is selected from H and Ci-e alkyl; orR4and one of L2, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl;R5is selected from H, halo, -CN, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, and Ci-6 haloalkoxy;R6is selected from H, halo, -CN, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, and Ci-6 haloalkoxy;R7is selected from H, halo, -CN, Ci-6 alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, and Ci-6 haloalkoxy; and each RGis independently selected from H, OH, CN, halo, oxo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl.

71. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein: m is 0, 1, 2, or 3; p is 1, 2, 3, 4, or 5; q is 0 or 1; r is 1 or 2; t is 0 or 1;Z1is N or CR3;Z2is N or CR4;X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;Y1is CR5;Y2is CR6;Y3is CR7;54057 -0028 WO 1 / SNV0021-W01 PATENTRing A is phenyl;Ring B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from Ci-e alkylene, -N(RL2c)-, and -C(O)-; each RL2cis independently selected from H and Ci-e alkyl;R20is selected from C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents; each R1is independently selected from halo, Ci-e alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, 5-10 membered heteroaryl, and -ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; each Ralis independently selected from H, Ci-e alkyl, and C1-6 haloalkyl; each R1Ais independently selected from oxo, Ci-e alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA, wherein the Ci-e alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-Ci.4 alkyl, and (5-6 membered heteroaryl)-Ci-4 alkyl of R1Aare each optionally substituted with 1 or 2 independently selected R1Bsubstituents; each RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, and C3-7 cycloalkyl-Ci-4 alkyl; each R1Bis independently selected from Ci-e alkyl, CN, and -C(O)NRclBRdlB, wherein the C1-6 alkyl of R1Bis optionally substituted with ORalB; each RalB, RclB, and RdlBis independently selected from H, Ci-e alkyl, and C3-7 cycloalkyl, wherein the C3-7 cycloalkyl of RalB, RclB, and RdlBis optionally substituted with CN; each R2is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, and - NRc2Rd2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce- 10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents;54057 -0028 WO 1 / SNV0021-W01 PATENT each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; each R2Ais independently selected from oxo, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H and Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl;R3is selected from H and Ci-e alkyl;R4is selected from H and Ci-e alkyl; orR4and one of L2, together with the atoms to which they are attached to form a 4-7 membered heterocycloalkyl;R5is selected from H and C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;R6is selected from H, Ci-e alkyl, and halo;R7is selected from H, Ci-e alkyl, and halo; and each RGis independently selected from H, OH, CN, halo, oxo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl.

72. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein: m is 0, 1, 2, or 3; p is 1, 2, 3, 4, or 5; q is 0 or 1; r is 1 or 2; t is 0 or 1;Z1is N or CR3;Z2is N or CR4;X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;Y1is CR5;Y2is CR6;Y3is CR7;Ring A is C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, or 5-6 membered heteroaryl;Ring B is a 5-membered heteroaryl;54057 -0028 WO 1 / SNV0021-W01 PATENT each L1, L2, L3, and L4are independently selected from Ci-e alkylene, -N(RL2c)-, and -C(O)-; each RL2cis independently selected from H and Ci-e alkyl;R20is selected from C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl, wherein the C3-14 cycloalkyl, Ce-io aryl, 4-14 membered heterocycloalkyl, and 5-10 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2substituents; each R1is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, -CN, -ORal, and -NRclRdl, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R1Asubstituents; each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R1Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRelARdlA. each RalA, RclA, and RdlAis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R2is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, and - NRc2Rd2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce- 10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; each R2Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents;54057 -0028 WO 1 / SNV0021-W01 PATENT each Ra2A, Rc2A, and Rd2Ais independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-e alkynyl, and C1-6 haloalkyl;R3is selected from H and Ci-e alkyl;R4is selected from H and Ci-e alkyl; orR4and one of L2, together with the atoms to which they are attached to, form a C3-10 cycloalkyl or 4-10 membered heterocycloalkyl;R5is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;R6is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;R7is selected from H, halo, -CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy; and each RGis independently selected from H, OH, CN, halo, oxo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1-4 alkoxy-Ci.4 alkyl.

73. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein: m is 0, 1, 2, or 3; p is 1, 2, 3, 4, or 5; q is 0 or 1; r is 1 or 2; t is 0 or 1;Z1is N or CR3;Z2is N or CR4;X1, X2, X3, X4are each independently N or C, wherein one of X1, X2, X3, and X4is N, and three of X1, X2, X3, and X4are C;Y1is CR5;Y2is CR6;Y3is CR7;Ring A is phenyl;Ring B is a 5-membered heteroaryl; each L1, L2, L3, and L4are independently selected from C1-6 alkylene, -N(RL2c)-, and - C(O)-; each RL2cis independently selected from H and C1-6 alkyl;R20is selected from C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl, wherein the C3-7 cycloalkyl, phenyl, 4-7 membered heterocycloalkyl,54057 -0028 WO 1 / SNV0021-W01 PATENT and 5-6 membered heteroaryl of R20are each optionally substituted with 1, 2, 3, or 4 independently selected R2substituents; each R1is independently selected from halo, Ci-e alkyl, Ci-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, 5-6 membered heteroaryl, and -ORal, wherein the C1-6 alkyl, C1-6 haloalkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, and 5-6 membered heteroaryl of R1are each optionally substituted with 1, 2, 3, or 4 independently selected R1Asubstituents; each Ral, Rcl, and Rdlis independently selected from H, Ci-e alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl; each R1Ais independently selected from oxo, Ci-e alkyl, C1-6 haloalkyl, (5-6 membered heteroaryl)-Ci-4 alkyl, -CN, -ORalA, and -NRclARdlA; each RalA, RclA, and RdlAis independently selected from H and Ci-e alkyl; each R2is independently selected from halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce-io aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -Ci -4 alkyl, (5-10 membered heteroaryl)-Ci-4 alkyl, -CN, -ORa2, and - NRc2Rd2, wherein the Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, Ce- 10 aryl, 4-10 membered heterocycloalkyl, 5-10 membered heteroaryl, C3-10 cycloalkyl-Ci-4 alkyl, Ce-io aryl-Ci-4 alkyl, (4-10 membered heterocycloalkyl) -C 1-4 alkyl, and (5-10 membered heteroaryl)-Ci-4 alkyl of R2are each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R2Asubstituents; each Ra2, Rc2, and Rd2is independently selected from H, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl; each R2Ais independently selected from oxo, halo, Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, Ci-6haloalkyl, -CN, -ORa2A, -NRc2ARd2A, and -C(O)NRc2ARd2A, wherein the Ci-6alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci-6 haloalkyl of R2Aare each optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected RGsubstituents; each Ra2A, Rc2A, and Rd2Ais independently selected from H and Ci-e alkyl, C2-6 alkenyl, C2-6 alkynyl, and Ci-6 haloalkyl;R3is selected from H and Ci-e alkyl;R4is selected from H and Ci-e alkyl; orR4and one of L2, together with the atoms to which they are attached to form a 4-7 membered heterocycloalkyl;R5is selected from H and Ci-e alkyl, Ci-6 haloalkyl, Ci-6 alkoxy, and Ci-6 haloalkoxy;R6is selected from H, Ci-e alkyl, and halo;R7is selected from H, Ci-e alkyl, and halo; and54057 -0028 WO 1 / SNV0021-W01 PATENT each RGis independently selected from H, OH, CN, halo, oxo, Ci-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 haloalkyl, cyano-Ci.4 alkyl, HO-C1.4 alkyl, C1.4 alkoxy-Ci.4 alkyl.

74. The compound of claim 1, wherein the compound of Formula I is a compound of Formula II:or a pharmaceutically acceptable salt thereof.

75. The compound of claim 1, wherein the compound of Formula I is a compound ofFormula III:or a pharmaceutically acceptable salt thereof.

76. The compound of claim 1, wherein the compound of Formula I is a compound ofFormula IV:54057 -0028 WO 1 / SNV0021-W01 PATENTIV or a pharmaceutically acceptable salt thereof.

77. The compound of claim 1, wherein the compound of Formula I is a compound ofFormula V:V or a pharmaceutically acceptable salt thereof.

78. The compound of claim 1, wherein the compound of Formula I is a compound of Formula VI:54057 -0028 WO 1 / SNV0021-W01 PATENTor a pharmaceutically acceptable salt thereof.

79. The compound of claim 1, wherein the compound of Formula I is a compound of Formula VII:or a pharmaceutically acceptable salt thereof.

80. The compound of claim 1, wherein the compound of Formula I is a compound of Formula VIII:54057 -0028 WO 1 / SNV0021-W01 PATENTor a pharmaceutically acceptable salt thereof.

81. The compound of claim 1, which is selected from:(10R)-9-(difluoromethoxy)-13-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2,3- dihydro-lH-10,16b-methanobenzo[f]benzo[4,5]imidazo[l,2-a]pyrrolo[2,l-c][l,4]diazocin- 5(10H)-one;( 1 OR)- 13 -(2-( 1 -aminocyclobutyl)pyrimidin-5 -yl)-9-(difluoromethoxy)-2,3 -dihydro- lH-10,16b-methanobenzo[f]benzo[4,5]imidazo[l,2-a]pyrrolo[2,l-c][l,4]diazocin-5( 10H)- one;2-(5 -( 1 -(difluoromethoxy) -5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-ll-yl)pyrimidin-2-yl)propan-2-ol;( 10R)-9-(difluoromethoxy)- 13 -(4-(( 1 R,5 S)-3 -methyl-3 -azabicyclo [3.1.0]hexan- 1 - yl)phenyl)-2,3 -dihydro- 1H- 10,16b-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a]pyrrolo [2, 1 - c] [ 1 ,4]diazocin-5( 10H)-one;5 -( 1 -(difluoromethoxy) -5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-ll-yl)-3-fluoropyridin-2 -amine;1 -(difhroromethoxy)- 12-(2-(2 -hydroxypropan -2 -yl)pyrimidin-5 -yl)-5 , 15 -dihydro- 6H,8H-7,15-methanobenzo[g]benzo[4,5]imidazo[l,2-a][l,4]diazonin-6-one;1 -(difhroromethoxy)- 12-(2-(2 -hydroxypropan -2 -yl)pyrimidin-5 -yl)-5 , 15 -dihydro- 6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;(7R, 15R)- 1 -(difluoromethoxy)- 12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-7,8- dihydro-6H-7,15-methanobenzo[g]benzo[4,5]imidazo[l,2-a][l,5]diazonin-5(15H)-one; and(7R, 15R)- 1 -(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-6- methyl-7,8-dihydro-6H-7,15-methanobenzo[g]benzo[4,5]imidazo[l,2-a][l,5]diazonin- 5(15H)-one;54057 -0028 WO 1 / SNV0021-W01 PATENT or a pharmaceutically acceptable salt thereof.

82. The compound of claim 1, wherein the compound is selected from:2-(5-(l-(difluoromethoxy)-4-(l-methyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;2-(5-(l-(difluoromethoxy)-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;2-(5-(l-(difluoromethoxy)-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;2-(5-(l-(difhroromethoxy)-4-(l-(difluoromethyl)-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;2-(5-(l-(difluoromethoxy)-4-(l-ethyl-lH-pyrazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;2-(5-(l-(difluoromethoxy)-4-(2-methyloxazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;2-(5-(l-(difluoromethoxy)-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;2-(5-(l-(difluoromethoxy)-2-methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;2-(5-(l-(difhioromethoxy)-2-methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;2-(5-(l-(difhioromethoxy)-4-(methoxymethyl)-2-methyl-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;2-(5-(l-(difhroromethoxy)-2-methyl-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;2-(5 -( 1 -(difhroromethoxy)-4-(hydroxymethyl)-2-methyl-5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-pyrazol-4-yl)-5 , 14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;54057 -0028 WO 1 / SNV0021-W01 PATENT2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol;2-(5-(l-(difluoromethoxy)-2-fluoro-4-(methoxymethyl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyloxazol-5-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;6-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-2- methylpyridazin-3 (2H) -one ;2-(5 -(4-(5 -amino- 1 -methyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro-5 ,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol;2-(5-(l-(difluoromethoxy)-4-(l-ethyl-lH-pyrazol-3-yl)-2-fluoro-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- 1H- 1 ,2,4-triazol-3 -yl)-5 , 14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol;2-(5-( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -(pyridin-3-yhnethyl)- lH-pyrazol-4-yl)-5, 14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;2-(5 -( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -methyl- lH-imidazol-4-yl)-5 , 14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)tetrahydrofuran-3 -ol ;54057 -0028 WO 1 / SNV0021-W01 PATENT4-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)tetrahydro-2H-pyran-4-ol;5-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-5- methylimidazolidine-2, 4-dione;2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propane- 1,2-diol;3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)-3-fluoropyridin-2-yl)-3- hydroxy- 1 -methylcyclobutane - 1 -carbonitrile ;2-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6.14-methanobenzo[f]benzo[4,5]imidazo[ 1 ,2-a] [ 1 ,4]diazocin- 11 -yl)pyrimidin-2-yl)- 1 - methoxypropan-2-ol;3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- hydroxybutanenitrile ;(l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)cyclobutyl)methanol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)cyclobutan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2-yl)- 1 -( 1 - methyl- lH-pyrazol-4-yl)ethan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)cyclobutane- 1 -carboxamide; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)piperidin-4-ol;(3-amino-3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)- 1 -methylcyclobutyl)methanol;54057 -0028 WO 1 / SNV0021-W01 PATENT(3-amino-3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5.14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)- 1 -methylcyclobutyl)methanol;3-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6.14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)tetrahydrofuran-3 -amine ;3 -amino-3 -(5 -( 1 -(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5 -yl)-5 ,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)- 1 -methylcyclobutan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- (hydroxymethyl) -3 -methylcyclobutan- 1 -ol ; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- (hydroxymethyl)cyclobutan- 1 -ol; l-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)-3- methylcyclobutane - 1 , 3 -diol;1-(5-(l-(difluoromethoxy)-2-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2- yl)cyclobutane - 1 , 3 -diol ;1 -( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-5 ,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)pyrrolidine-3- carbonitrile;2-(5 -( 1 -(difluoromethoxy)- 10-fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;2-(5-(l-(difluoromethoxy)-10-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;2-(5-(l-(difluoromethoxy)-9-fluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;2-(5 -( 1 -(difluoromethoxy)-9-fluoro-4-( 1 -methyl- lH-pyrazol-3 -yl) -5 , 14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2- ol;54057 -0028 WO 1 / SNV0021-W01 PATENT2-(5-(l-(difluoromethoxy)-2,9-difluoro-4-(2-methyl-2H-tetrazol-5-yl)-5,14-dihydro- 7H-6, 14-methanobenzo[f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol;2-(5-(l-(difluoromethoxy)-2,9-difluoro-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro- 7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [ 1 ,2-a] [ 1 ,4] diazocin- 11 -yl)pyrimidin-2- yl)propan-2-ol; l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2-methyl-5,15- dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2,4-dimethyl-5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;1 -(difluoromethoxy)- 12-(2-(2 -hydroxypropan -2 -yl)pyrimidin-5 -yl)-2 -methyl -4-( 1 - methyl-lH-pyrazol-3-yl)-5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l- e] [ 1 ,3 ,6]triazonin-6-one;1-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2-methyl-4-(2- methyl -2H- 1 ,2,3 -triazol-4-yl)-5 , 15 -dihydro-6H,8H-7, 15- methanobenzo[h]benzo[4,5]imidazo[2, 1 -e] [ l,3,6]triazonin-6-one;1 -(difluoromethoxy)-4-fluoro- 12-(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl) -5 ,15- dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;2-cyclopropyl-l-(difluoromethoxy)-4-fluoro-12-(2-(2-hydroxypropan-2-yl)pyrimidin- 5 -yl) -5 , 15 -dihydro-6H, 8H-7, 15 -methanobenzo [h]benzo [4,5] imidazo[2, 1 -e] [ 1 ,3 ,6]triazonin-6- one;12-(2-(2 -aminopropan -2 -yl)pyrimidin-5-yl)-l-(difluoromethoxy)-4-fluoro-2 -methyl-5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; l-(difluoromethoxy)-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-2,5-dimethyl-5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;1 -(difluoromethoxy)- 12-(2-(3 -hydroxy oxetan-3 -yl)pyrimidin-5 -yl)-2, 5 -dimethyl -5,15-dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one;12-(2-(2 -aminopropan -2 -yl)pyrimidin-5 -yl)- 1 -(difluoromethoxy)-2,5 -dimethyl-5 ,15- dihydro-6H,8H-7,15-methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; l-(difluoromethoxy)-2-fluoro-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-4- methyl-5 , 15 -dihydro-6H, 8H-7, 15 -methanobenzo [h]benzo [4,5]imidazo [2, 1 -e] [ 1 ,3 ,6]triazonin- 6-one; l-(difluoromethoxy)-2-fluoro-12-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-4-(2- methyl-2H- 1 ,2,3 -triazol-4-yl)-5 , 15 -dihydro-6H,8H-7, 15- methanobenzo[h]benzo[4,5]imidazo[2,l-e][l,3,6]triazonin-6-one; and54057 -0028 WO 1 / SNV0021-W01 PATENT2-(5 -( 1 -(difluoromethoxy)- 1 OH, 17H-9, 17 -methanobenzo [h]benzo [4,5]imidazo [2, 1 - e]imidazo[l,2-a][l,3,6]triazonin-14-yl)pyrimidin-2-yl)propan-2-ol; or a pharmaceutically acceptable salt thereof.

83. The compound of claim 1, which is selected from:1 -( (4 -( 1 -(difluoromethoxy)-2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)methyl)cyclopropane- 1 -carbonitrile;5 -(4-( 1 -(difluoromethoxy)-2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)picolinonitrile;2-(5 -( 1 -(difluoromethoxy)-4-(6,7-dihydro-5H-pyrazolo [5 , 1 -b] [ 1 ,3] oxazin-3 -yl)-2- fluoro-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)propan-2-ol;5-(3-(l-(difluoromethoxy)-2-fluoro-l l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- 1 ,2,4-triazol- 1 -yl)picolinonitrile;5-(3-(l-(difluoromethoxy)-2-fluoro-l l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)picolinonitrile;2-(5-( 1 -(difluoromethoxy)-2-fluoro-4-( 1 -(6-(hydroxymethyl)pyridin-3-yl)-lH- pyrazol-4-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin- 1 l-yl)pyrimidin-2-yl)propan-2-ol;6-(4-( 1 -(difluoromethoxy)-2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)nicotinonitrile;N-cyclopropyl-5-(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- IH-pyrazol- 1 -yl)pyrimidine-2 -carboxamide;N-cyclopropyl-5-(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- IH-pyrazol- 1 -yl)picolinamide;N-( 1 -cyanocyclopropyl)-5-(4-( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2- hydroxypropan-2-yl)pyrimidin-5-yl)-5, 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH-pyrazol-l-yl)picolinamide;54057 -0028 WO 1 / SNV0021-W01 PATENT6-(3 -( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)-5.14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-lH- pyrazol- 1 -yl)nicotinonitrile;2-(5-(4-(2-(cyclopropylmethyl)-2H-tetrazol-5-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;2-(5-(l-(difluoromethoxy)-2-fluoro-4-(4,5,6,7-tetrahydropyrazolo[l,5-a]pyrimidin-2- yl)-5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)propan-2-ol;5 -(5 -amino-3 -( 1 -(difluoromethoxy)-2 -fluoro- 11 -(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- IH-pyrazol- 1 -yl)-N-cyclopropylpicolinamide;2-(5 -(4-(5 -((cyclopropylmethyl)amino)- 1 -methyl- lH-pyrazol-3 -yl)- 1 - (difluoromethoxy)-2-fluoro-5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo[4,5] imidazo [1,2- a] [ 1 ,4]diazocin- 11 -yl)pyrimidin-2-yl)propan-2-ol;2-(5-(4-([l,2,4]triazolo[l,5-a]pyrazin-2-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;2-(5-(4-([l,2,4]triazolo[l,5-a]pyrimidin-2-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;2-(5-(4-(5-amino-l-methyl-lH-l,2,4-triazol-3-yl)-l-(difluoromethoxy)-2-fluoro-5,14- dihydro-7H-6, 14-methanobenzo[f]benzo[4,5]imidazo[l,2-a] [ 1,4] diazocin- 1 l-yl)pyrimidin-2- yl)propan-2-ol;N-cyclopropyl-5 -(3 -( 1 -(difluoromethoxy) -2 -fluoro- 11 -(2-(2-hydroxypropan-2- yl)pyrimidin-5 -yl) -5 , 14-dihydro-7H-6, 14-methanobenzo [f]benzo [4,5]imidazo [1,2- a] [ 1 ,4]diazocin-4-yl)- 1H- 1 ,2,4-triazol- 1 -yl)picolinamide;2-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-6,7-dihydro- [ 1 ,2,4]triazolo [1,5 -a]pyrimidin-5 (4H)-one;2-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-6,7- dihydropyrazolo [ 1 ,5 -a]pyrimidin-5 (4H)-one ;2-(5 -(4-(5 -amino- 1 -cyclopropyl- lH-pyrazol-3 -yl)- 1 -(difluoromethoxy)-2-fluoro-5.14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l 1- yl)pyrimidin-2-yl)propan-2-ol;54057 -0028 WO 1 / SNV0021-W01 PATENT1 -((5 -( 1 -(difluoromethoxy)-2 -fluoro- 11 -(2-(2-hydroxypropan-2-yl)pyrimidin-5 -yl)- 5,14-dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-2H- tetrazol-2-yl)methyl)cyclopropane- 1 -carbonitrile; and2-(l-(difluoromethoxy)-2 -fluoro- 1 l-(2-(2-hydroxypropan-2-yl)pyrimidin-5-yl)-5,14- dihydro-7H-6,14-methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-4-yl)-5-methyl-6,7- dihydropyrazolo [ 1 ,5 -a]pyrazin-4(5H)-one ; or a pharmaceutically acceptable salt thereof.

84. In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- methyl-4-(l-methyl-lH-pyrazol-3-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

85. In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- methyl-4-(2-methyl-2H-l,2,3-triazol-4-yl)-5,14-dihydro-7H-6,14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

86. In some embodiments, the compound provided herein is 2-(5-(l-(difluoromethoxy)-2- methyl-4-(2-methyl-2H-tetrazol-5-yl)-5, 14-dihydro-7H-6, 14- methanobenzo[f]benzo[4,5]imidazo[l,2-a][l,4]diazocin-l l-yl)pyrimidin-2-yl)propan-2-ol, or a pharmaceutically acceptable salt thereof.

87. A pharmaceutical composition, comprising a compound of any one of claims 1 to 86, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

88. A method of inhibiting an activity of tumor necrosis factor-alpha (TNFa), comprising contacting the TNFa with a compound of any one of claims 1 to 86, or a pharmaceutically acceptable salt thereof.

89. A method of treating a TNFa-mediated disease or disorder in a patient, comprising administering to the patient a therapeutically effective amount of a compound of any one of claims 1 to 86, or a pharmaceutically acceptable salt thereof.

90. The method of claim 89, wherein the disease or disorder is and autoimmune disease or inflammatory disease.54057 -0028 WO 1 / SNV0021-W01 PATENT91. The method of claim 90, wherein the inflammatory disease is a chronic inflammatory disease.

92. The method of any one of claims 89 to 91, wherein the disease or disorder is neurodegenerative disease associated with TNF-a related inflammation and apoptosis.

93. The method of any one of claims 89 to 92, wherein the disease or disorder is selected from plaque psoriasis, rheumatoid arthritis (RA), psoriatic arthritis (PsA), Crohn’s disease (CD), ulcerative colitis (UC), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), hidradenitis suppurativa (HS), uveitis, sarcoidosis, Behcet's disease, granulomatosis with polyangiitis, Alzheimer's disease, Parkinson's disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease, traumatic brain injury, and neuromyelitis optica spectrum disorder (NMOSD).

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