IP Library › Granted Patent US 9,695,167

Granted Patent B2

US 9,695,167 · App. 14/795,499 · Granted Jul 4, 2017

Substituted triazolo[1,5-a]pyridines and triazolo[1,5-a]pyrazines as LSD1 inhibitors

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Patent No.: US 9,695,167
App. No.: 14/795,499
Granted: Jul 4, 2017
Kind: B2

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Abstract

The present invention is directed to [1,2,4]triazolo[1,5-a]pyridine and [1,2,4]triazolo[1,5-a]pyrazine derivatives of Formula I, or a pharmaceutically acceptable salt thereof, which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

Claims (130)

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

X is N or CR X ;

Ring A is C 6-10 aryl or 5-10 membered heteroaryl comprising carbon and 1, 2, 3, or 4 heteroatoms selected from N, O, and S, wherein said C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R A ;

Ring B is C 6-10 aryl; 5-10 membered heteroaryl comprising carbon and 1, 2, 3 or 4 heteroatoms selected from N, O, and S; C 3-10 cycloalkyl; or 4-10 membered heterocycloalkyl comprising carbon and 1, 2, 3 or 4 heteroatoms selected from N, O, and S; wherein said C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R B ;

R 1 is halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, Cy 1 , CN, OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , C(═NR e1 )R b1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , or S(O) 2 NR c1 R d1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy 1 , halo, CN, OR a1 , SR a1 C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , C(═NR e1 )R b1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ;

wherein when X is CR X , then R 1 is not CN;

R 2 is H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, Cy 2 , CN, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , C(═NR e2 )R b2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , or S(O) 2 NR c2 R d2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy 2 , halo, CN, OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , C(═NR e2 )R b2 , C(═NR e2 )NR c2 R d2 NR c2 C(═NR e2 )NR c2 R d2 NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ;

each R A is independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, NO 2 , OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)OR a4 , NR c4 C(O)NR c4 R d4 , C(═NR e4 )R b4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 , NR c4 S(O)R b4 , NR c4 S(O) 2 R b4 , NR c4 S(O) 2 NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , and S(O) 2 NR c4 R d4 , wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted by 1, 2, or 3, substituents independently selected from halo, C 1-6 haloalkyl, CN, NO 2 , OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)OR a4 , NR c4 C(O)NR c4 R d4 , C(═NR e4 )R b4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 NR c4 S(O)R b4 , NR c4 S(O) 2 R b4 , NR c4 S(O) 2 NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , and S(O) 2 NR c4 R d4 ;

each R B is independently selected from Cy 3 , halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, NO 2 , OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 C(O)NR c5 R d5 , C(═NR e5 )R b5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , NR c5 S(O)R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d6 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , and S(O) 2 NR c5 R d5 , wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted by 1, 2, or 3 substituents independently selected from Cy 3 , halo, C 1-6 haloalkyl, CN, NO 2 , OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 C(O)NR c5 R d5 , C(═NR e5 )R b5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , NR c5 S(O)R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ;

R X is independently selected from H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)OR a7 , NR c7 C(O)NR c7 R d7 , C(═NR e7 )R b7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , NR c7 S(O)R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , and S(O) 2 NR c7 R d7 ;

each Cy 1 , Cy 2 , Cy 3 , and Cy 4 is independently selected from C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R Cy ;

each R Cy is independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl-, C 3-7 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, and (4-7 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , C(═NR e6 )NR c6 R d6 , NR c6 C(═NR e6 )NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , NR c6 C(O)NR c6 R d6 , NR c6 S(O)R b6 , NR c6 S(O) 2 R b6 , NR c6 S(O) 2 NR c6 R d6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 , wherein said C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl-, C 3-7 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, and (4-7 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted by 1, 2, or 3 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, NO 2 , OR a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , C(═NR e6 )NR c6 R d6 , NR c6 C(═NR e6 )NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , NR c6 C(O)NR c6 R d6 , NR c6 S(O)R b6 , NR c6 S(O) 2 R b6 , NR c6 S(O) 2 NR c6 R d6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 ;

each R a1 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and Cy 4 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy 4 , halo, CN, OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 C(O)NR c3 R d3 , C(═NR e3 )R b3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;

each R b1 , R c1 , and R d1 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

or any R c1 and R d1 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

each R a2 , R b2 , R c2 , and R d2 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

or any R c2 and R d2 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c R d7 , and S(O) 2 NR c7 R d7 ;

each R a3 , R b3 , R c3 , and R d3 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R c7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

or any R c3 and R d3 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

each R a4 , R b4 , R c4 , and R d4 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

or any R c4 and R d4 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

each R a5 , R b5 , R c5 , and R d5 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

or any R c5 and R d5 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR C7 R d7 , and S(O) 2 NR c7 R d7 ;

each R a6 , R b6 , R c6 , and R d6 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

or any R c6 and R d6 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

each R a7 , R b7 , R c7 , and R d7 is independently selected from H, C 1-4 alkyl, C 1-4 haloalkyl, C 2-4 alkenyl, and C 2-4 alkynyl, wherein said C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylthio, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 haloalkyl, and C 1-4 haloalkoxy; and

each R e1 , R e2 , R e3 , R e4 , R e5 , R e6 , and R e7 is independently selected from H, C 1-4 alkyl, and CN.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

X is N or CR X ;

Ring A is phenyl or 5-10 membered heteroaryl comprising carbon and 1, 2, 3, or 4 heteroatoms selected from N, O, and S, wherein said C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R A ;

Ring B is phenyl or 5-6 membered heteroaryl comprising carbon and 1, 2, 3 or 4 heteroatoms selected from N, O, and S; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R B ;

R 1 is halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, Cy 1 , CN, OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , C(═NR e1 )R b1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , or S(O) 2 NR c1 R d1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy 1 , halo, CN, OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , C(═NR e1 )R b1 , C(═NR e1 )R c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ;

wherein when X is CR X , then R 1 is not CN;

R 2 is H, halo, C 1-6 alkyl, CN, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , NR c2 R d2 NR c2 C(O)R b2 , S(O) 2 R b2 , or S(O) 2 NR c2 R d2 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ;

each R A is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, OR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , NR c4 R d4 , NR c4 C(O)R b4 , S(O) 2 R b4 , and S(O) 2 NR c4 R d4 , wherein said C 1-6 alkyl is optionally substituted by 1, 2, or 3, substituents independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, OR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , NR c4 R d4 , NR c4 C(O)R b4 , S(O) 2 R b4 , and S(O) 2 NR c4 R d4 ;

each R B is independently selected from Cy 3 , halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, NO 2 , OR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , NR c5 R d5 , NR c5 C(O)R b5 , S(O) 2 R b5 , and S(O) 2 NR c5 R d5 , wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted by 1, 2, or 3 substituents independently selected from Cy 3 , halo, C 1-6 haloalkyl, CN, NO 2 , OR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , NR c5 R d5 , NR c5 C(O)R b5 , S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ;

R X is independently selected from H, halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, OR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , NR c7 R d7 , NR c7 C(O)R b7 , S(O) 2 R b7 , and S(O) 2 NR c7 R d7 ;

each Cy 1 , Cy 3 , and Cy 4 is independently selected from C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R Cy ;

each R a1 is independently selected from H, C 1-6 alkyl, and Cy 4 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 4 , halo, CN, OR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;

or any R c1 and R d1 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

each R a2 , R b2 , R c2 , and R d2 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

or any R c2 and R d2 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c R d7 , and S(O) 2 NR c7 R d7 ;

each R a3 , R b3 , R c3 , and R d3 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 and S(O) 2 NR c7 R d7 ;

or any R c3 and R d3 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

each R a4 , R b4 , R c4 , and R d4 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

or any R c4 and R d4 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

each R a5 , R b5 , R c5 , and R d5 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , R c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

or any R c5 and R d5 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 , NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

each R a6 , R b6 , R c6 , and R d6 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

or any R c6 and R d6 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 NR c7 C(O)OR a7 , C(═NR e7 )NR c7 R d7 , NR c7 C(═NR e7 )NR c7 R d7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

each R e1 , R e6 , and R e7 is independently selected from H, C 1-4 alkyl, and CN.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

X is N or CR X ;

Ring A is phenyl optionally substituted by 1 or 2 substituents independently selected from R A ;

Ring B is phenyl optionally substituted by 1 or 2 substituents independently selected from R B ;

R 1 is halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, Cy 1 , OR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , S(O) 2 R b1 , or S(O) 2 NR c1 R d1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy 1 , halo, CN, OR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , NR c1 R d1 , NR c1 C(O)R b1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ;

R 2 is H;

each R A is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, and OR a4 , wherein said C 1-6 alkyl is optionally substituted by 1, 2, or 3, substituents independently selected from CN and OR a4 ;

each R B is independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, and OR a5 ;

R X is H;

each Cy 1 and Cy 4 is independently selected from phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R Cy ;

each R Cy is independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, C 2-6 alkenyl, C 2-6 alkynyl, CN, NO 2 , OR a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , NR c6 C(O)NR c6 R d6 , NR c6 S(O)R b6 , NR c6 S(O) 2 R b6 , NR c6 S(O) 2 NR c6 R d6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 , wherein said C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, are each optionally substituted by 1, 2, or 3 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, NO 2 , OR a6 , SR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , NR c6 C(O)NR c6 R d6 , NR c6 S(O)R b6 , NR c6 S(O) 2 R b6 , NR c6 S(O) 2 NR c6 R d6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 ;

each R a1 is independently selected from H, C 1-6 alkyl, and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 4 , halo, CN, OR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 , and wherein said 4-7 membered heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , NR c6 R d6 , NR c6 C(O)R b6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 ;

each R b1 , R c1 , and R d1 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl-, C 3-7 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, and (4-7 membered heterocycloalkyl)-C 1-4 alkyl-, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, phenyl-C 1-4 alkyl-, C 3-7 cycloalkyl-C 1-4 alkyl-, (5-6 membered heteroaryl)-C 1-4 alkyl-, and (4-7 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c7 R d7 NR c7 C(O)OR a7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

or any R c1 and R d1 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 NR c7 C(O)R b7 , NR c7 C(O)NR c R d7 , NR c7 C(O)OR a7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, and 5-6 membered heteroaryl are each optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a7 , SR a7 , C(O)R b7 , C(O)NR c7 R d7 , C(O)OR a7 , OC(O)R b7 , OC(O)NR c7 R d7 , NR c7 R d7 , NR c7 C(O)R b7 , NR c7 C(O)NR c R d7 , NR c7 C(O)OR a7 , S(O)R b7 , S(O)NR c7 R d7 , S(O) 2 R b7 , NR c7 S(O) 2 R b7 , NR c7 S(O) 2 NR c7 R d7 , and S(O) 2 NR c7 R d7 ;

each R a3 , R b3 , R c3 , and R d3 is independently selected from H and C 1-6 alkyl;

each R a4 is independently selected from H and C 1-6 alkyl;

each R a5 is independently selected from H and C 1-6 alkyl;

each R a6 , R b6 , R c6 , and R d6 is independently selected from H and C 1-6 alkyl; and

each R a7 , R b7 , R c7 , and R d7 is independently selected from H and C 1-4 alkyl.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is N.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is CR X .

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R X is H.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl or 5-10 membered heteroaryl comprising carbon and 1, 2, 3, or 4 heteroatoms selected from N, O, and S, wherein said phenyl and 5-10 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R A .

8. The compound of claim 1 or claim 2 , or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl optionally substituted by 1 or 2 substituents independently selected from R A .

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl substituted by one R A .

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring A is phenyl substituted by CN.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is phenyl or 5-6 membered heteroaryl comprising carbon and 1, 2, 3 or 4 heteroatoms selected from N, O, and S; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted by 1, 2, 3, or 4 substituents independently selected from R B .

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is phenyl optionally substituted by 1 or 2 substituents independently selected from R B .

13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is phenyl substituted by one R B .

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ring B is phenyl substituted by CH 3 .

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R A is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, OR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , NR c4 R d4 , NR c4 C(O)R b4 , S(O) 2 R b4 , and S(O) 2 NR c4 R d4 , wherein said C 1-6 alkyl is optionally substituted by 1, 2, or 3, substituents independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, OR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , NR c4 R d4 , NR c4 C(O)R b4 , S(O) 2 R b4 , and S(O) 2 NR c4 R d4 .

16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R A is independently selected from halo, C 1-6 alkyl, C 1-6 haloalkyl, CN, and OR a4 , wherein said C 1-6 alkyl is optionally substituted by 1, 2, or 3, substituents independently selected from CN and OR a4 .

17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R A is CN.

18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R B is independently selected from Cy 3 , halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, NO 2 , OR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , NR c5 R d5 , NR c5 C(O)R b5 , S(O) 2 R b5 , and S(O) 2 NR c5 R d5 , wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted by 1, 2, or 3 substituents independently selected from Cy 3 , halo, C 1-6 haloalkyl, CN, NO 2 , OR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , NR c5 R d5 , NR c5 C(O)R b5 , S(O) 2 R b5 , and S(O) 2 NR c5 R d5 .

19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R B is independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, CN, and OR a5 .

20. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R B is C 1-6 alkyl.

21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R B is CH 3 .

22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, Cy 1 , OR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , S(O) 2 R b1 , or S(O) 2 NR c1 R d1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy 1 , halo, CN, OR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , NR c1 R c1 , NR c1 C(O)R b1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 .

23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is C 1-6 alkyl, Cy 1 , or OR a1 , wherein said C 1-6 alkyl is substituted by one Cy 1 .

24. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is pyrrolidin-3-ylmethoxy, 2-pyrrolidin-3-ylethyl, (1-methylpyrrolidin-3-yl)ethyl, 3-[(methylamino)methyl]phenyl, 3-aminopyrrolidin-1-yl)methyl]phenyl, piperazin-1-ylmethyl, 4-methylpiperazin-1-yl)methyl, 3-(dimethylamino)pyrrolidin-1-yl, 3-(methylamino)pyrrolidin-1-yl, or (1-methylpyrrolidin-3-yl)methoxy.

25. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is H.

26. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each Cy 1 is independently selected from phenyl, C 3-7 cycloalkyl, 5-6 membered heteroaryl, and 4-7 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R.

27. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each Cy 1 is phenyl or 4-7 membered heterocycloalkyl, each optionally substituted with 1 or 2 substituents independently selected from R.

28. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each Cy 1 is phenyl, pyrrolidinyl, or piperazinyl, each optionally substituted with 1 or 2 substituents independently selected from R Cy .

29. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each Cy 1 is phenyl, pyrrolidinyl, or piperazinyl, each optionally substituted with 1 or 2 substituents independently selected from C 1-4 alkyl and NR c6 R d6 , wherein said C 1-4 alkyl is optionally substituted with NR c6 R d6 .

30. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Cy is C 1-4 alkyl and NR c6 R d6 , wherein said C 1-4 alkyl is optionally substituted with NR c6 R d6 .

31. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R a1 is independently selected from H, C 1-6 alkyl, and Cy 4 ; wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 4 , halo, CN, OR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 .

32. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R a1 is independently selected from H, C 1-6 alkyl, and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy 4 , halo, CN, OR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , NR c3 C(O)R b3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 , and wherein said 4-7 membered heterocycloalkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a6 , C(O)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , NR c6 R d6 , NR c6 C(O)R b6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 .

33. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R a1 is C 1-4 alkyl substituted by 4-7 membered heterocycloalkyl, wherein said 4-7 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a6 , C(O)R v6 , C(O)NR c6 R d6 , C(O)OR a6 , NR c6 R d6 , NR c6 C(O)R b6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 .

34. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R a1 is pyrrolidinylmethyl optionally substituted by one C 1-4 alkyl.

35. The compound of claim 1 having Formula IIa:

or a pharmaceutically acceptable salt thereof.

36. The compound of claim 1 having Formula IIb:

or a pharmaceutically acceptable salt thereof.

37. The compound of claim 1 having Formula IIIa:

or a pharmaceutically acceptable salt thereof.

38. The compound of claim 1 having Formula IIIb:

or a pharmaceutically acceptable salt thereof.

39. The compound of claim 1 selected from:

4-{5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy][1,2,4]triazolo[1,5-a]pyridin-6-yl}benzonitrile;

4-[5-(4-methylphenyl)-8-(2-pyrrolidin-3-ylethyl)[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzonitrile;

4-{5-(4-methylphenyl)-8-[2-(1-methylpyrrolidin-3-yl)ethyl][1,2,4]triazolo[1,5-a]pyridin-6-yl}benzonitrile;

4-[8-{3-[(methylamino)methyl]phenyl}-5-(4-methylphenyl)[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzonitrile;

4-[8-{3-[(3-aminopyrrolidin-1-yl)methyl]phenyl}-5-(4-methylphenyl)[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzonitrile;

4-[5-(4-methylphenyl)-8-(piperazin-1-ylmethyl)[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzonitrile;

4-{5-(4-methylphenyl)-8-[(4-methylpiperazin-1-yl)methyl][1,2,4]triazolo[1,5-a]pyridin-6-yl}benzonitrile;

4-[8-{[(3 S)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-5-(4-methylphenyl)-[1,2,4]triazolo-[1,5-a]pyridin-6-yl]benzonitrile;

4-[8-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-5-(4-methylphenyl)-[1,2,4]triazolo-[1,5-a]pyridin-6-yl]benzonitrile;

4-[8-{[(3 S)-3-(methylamino)pyrrolidin-1-yl]methyl}-5-(4-methylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzonitrile;

4-[8-{[(3R)-3-(methylamino)pyrrolidin-1-yl]methyl}-5-(4-methylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]benzonitrile;

4-{5-(4-methylphenyl)-8-[(3R)-pyrrolidin-3-ylmethoxy][1,2,4]triazolo[1,5-a]pyrazin-6-yl}benzonitrile; and

4-(5-(4-methylphenyl)-8-{[(3R)-1-methylpyrrolidin-3-yl]methoxy}[1,2,4]triazolo[1,5-a]pyrazin-6-yl)benzonitrile,

or a pharmaceutically acceptable salt of any of the aforementioned.

40. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

41. A method of inhibiting lysine specific demethylase-1 comprising contacting a compound of claim 1 , or a pharmaceutically acceptable salt thereof, with said lysine specific demethylase-1.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 10, 2021

From: INCYTE CORPORATION

To: INCYTE CORPORATION; INCYTE HOLDINGS CORPORATION

Reel/Frame 058815/0857 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 21, 2015

From: WU, LIANGXING; WANG, XIAOZHAO; YAO, WENQING; ZHANG, COLIN

To: INCYTE CORPORATION

Reel/Frame 036141/0150 →