Pyrazolopyridine compounds and uses thereof
Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is Cy 1 ;
Cy 1 is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl, wherein each 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ;
Cy A is C 6-10 aryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 20 ;
R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, OR a7 , SR 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 , NR c7 C(O)OR a7 , 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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 30 ;
each R 10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, NO 2 , 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(═NOR a1 )R b1 , C(═NR e1 )NR c1 R d1 , NR c1 (═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 said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;
or two R 10 substituents taken together with the carbon atom to which they are attached form a spiro 3-7-membered heterocycloalkyl ring, or a spiro C 3-6 cycloalkyl ring; wherein each spiro 3-7-membered heterocycloalkyl ring has at least one ring-forming carbon atom and 1, 2 or 3, ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of each spiro 3-7-membered heterocycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the spiro 3-7-membered heterocycloalkyl ring and spiro C 3-6 cycloalkyl ring are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 11 ;
each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, OR a3 , SR 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 , NR c3 C(O)OR a3 , 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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;
each R 12 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, CN, OR a5 , SR 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 , NR c5 C(O)OR a5 , 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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, NO 2 , 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(═NOR a2 )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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;
or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of the fused C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the fused C 3-7 cycloalkyl ring is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 ;
each R 21 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, OR a4 , SR 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 , NR c4 C(O)OR a4 , 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, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 22 ;
or two R 21 substituents taken together with the carbon atom to which they are attached form a spiro C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of the spiro C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the spiro C 3-7 cycloalkyl ring is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 22 ;
each R 22 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, CN, OR a6 , SR 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 , NR c6 C(O)OR a6 , 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 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R 30 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, CN, OR a8 , SR a8 , C(O)R b8 , C(O)NR c8 R d8 , C(O)OR a8 , NR c8 R d8 , NR c8 C(O)R b8 , NR c8 C(O)OR a8 , NR c8 S(O)R b8 , NR c8 S(O) 2 R b8 , NR c8 S(O) 2 NR c8 R d8 , S(O)R b8 , S(O)NR c8 R d8 , S(O) 2 R b8 , and S(O) 2 NR c8 R d8 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R a1 , R c1 and R d1 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;
or any R c1 and R d1 attached to the same N atom, 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, 3 or 4 substituents independently selected from R 11 ;
each R b1 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;
each R e1 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;
each R a2 , R c2 and R d2 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;
or any R c2 and R d2 attached to the same N atom, 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, 3 or 4 substituents independently selected from R 21 ;
each R b2 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;
each R e2 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;
each R a3 , R c3 and R d3 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;
or any R c3 and R d3 attached to the same N atom, 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 R 12 ;
each R b3 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl;
wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;
each R a4 , R c4 and R d4 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 22 ;
or any R c4 and R d4 attached to the same N atom, 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 R 22 ;
each R b4 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 22 ;
each R a5 , R c5 and R d5 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R b5 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R a6 , R c6 and R d6 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R b6 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R a7 , R c7 , and R d7 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 30 ;
or any R c7 and R d7 attached to the same N atom, 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 R 30 ;
each R b7 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 30 ;
each R a8 , R c8 and R d8 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
or any R c8 and R d8 attached to the same N atom, 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 R g ;
each R b8 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl;
wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; and
each R g is independently selected from OH, NO 2 , CN, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-2 alkylene, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-3 alkoxy-C 1-3 alkyl, C 1-3 alkoxy-C 1-3 alkoxy, HO—C 1-3 alkoxy, HO—C 1-3 alkyl, cyano-C 1-3 alkyl, H 2 N-C 1-3 alkyl, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, carboxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, aminosulfonyl, C 1-6 alkylaminosulfonyl, di(C 1-6 alkyl)aminosulfonyl, aminosulfonylamino, C 1-6 alkylaminosulfonylamino, di(C 1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6 alkylaminocarbonylamino, and di(C 1-6 alkyl)aminocarbonylamino.
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy A is phenyl optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 20 .
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, NO 2 , 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 , 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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 21 ; or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of each fused C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the fused C 3-7 cycloalkyl ring are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 .
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, NO 2 , 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 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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 21 ; or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of each fused C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the fused C 3-7 cycloalkyl ring are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 .
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl, 5-10 membered heteroaryl, halo, OR 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 , and NR c2 C(O)NR c2 R d2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 21 ; or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of each fused C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the fused C 3-7 cycloalkyl ring are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 .
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 R d2 , NR c2 C(O)R b2 , and NR c2 C(O)OR a2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 21 ; or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of each fused C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the fused C 3-7 cycloalkyl ring are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 .
7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, halo, 4-10 membered heterocycloalkyl, 4-10 membered heterocycloalkyl-C 1-3 alkylene, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , 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 , and NR c2 C(O)NR c2 R d2 ; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 4-10 membered heterocycloalkyl-C 1-3 alkylene are each optionally substituted with 1 or 2 substituents independently selected from R 21 ; or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused C 3-7 cycloalkyl ring; and wherein the fused C 3-7 cycloalkyl ring is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 .
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, halo, and OR a2 ; wherein said C 1-6 alkyl and C 3-10 cycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 21 ; or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused C 3-7 cycloalkyl ring; and wherein the fused C 3-7 cycloalkyl ring is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 .
9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from methyl, trifluoromethyl, cyclopropyl substituted with methanamine, fluoro, chloro, hydroxy, methoxy, ethoxy, C(O)NH(CH 2 ) 2 OCH 3 , CO-(3-methoxyazetidin-1-yl), NHC(O)-cyclobutyl, NHC(O)-benzyl, methylamino, dimethylamino, NHC(O)CH 2 -(pyrrolidin-1-yl), NHC(O)-(1-methyl-1H-pyrazol-4-yl), NH(CO)CH 2 -(cyclopentyl), NHC(O)CH 2 -(pyridin-3-yl), NHC(O)CH 2 -(7-azabicyclo[2.2.1]heptan-7-yl), NHC(O)-(7-oxa-2-azaspiro[3.5]nonan-2-yl), NHC(O)CH(CH 3 )-(pyrrolidin-1-yl), NHC(O)NH(CH 2 ) 2 OCH 3 , NHC(O)CH 2 -(azetidin-1-yl), NHC(O)CH 2 -(3,3-dimethylazetidin-1-yl), NHC(O)O-(1-methylpiperidin-4-yl), NHC(O)CH 2 -(dimethylamino), NHC(O)CH 2 -((1R,4S)-2-azabicyclo[2.2.1]heptan-2-yl), NHC(O)(CH 2 ) 2 -(dimethylamino), NHC(O)CH 2 CN, (methylamino)methyl, azetidin-1-ylmethyl, CH 2 NH-(tetrahydro-2H-pyran-4-yl), (isopropylamino)methyl, cyclobutyl-NHCH(CH 3 ) 2 , (methylamino)ethyl, (CH 2 ) 2 NH-(tetrahydro-2H-pyran-4-yl), (CH 2 ) 2 NH-(1-isopropylazetidin-3-yl), OCH 2 -(azetidin-2-yl), tetrahydro-2H-pyran-4-yloxy, OCH 2 -(pyridin-4-yl), OC(O)N(CH 3 ) 2 , OC(O)-(morpholin-4-yl), CH 2 NH-(pyridin-5-yl), CH 2 NH-(1-methyl-1H-pyrazol-3-yl), CH 2 NH(CH 2 ) 20 H, CH 2 NH-cyclopropyl, (3-methoxypiperidin-1-yl)methyl, (ethylamino)methyl, pyrrolidin-1-ylmethyl, 3-methoxyazetidin-1-yl)methyl, pyrrolidin-2-yl, 1-methylpyrrolidin-2-yl, piperidin-2-yl, CH 2 NHCH 2 CF 3 , CH 2 NH-(3-cyclobutan-1-ol), (1-pyrrolidin-3-ol)methyl, CH 2 NHCH 2 C(CH 3 ) 2 OH, CH 2 NHCH 2 -(1-methyl-1H-imidazol-4-yl), CH 2 NHCH 2 -(oxazol-4-yl), CH 2 NHCH 2 CN, CH(CH 3 )NH(CH 3 ), CH 2 NHC(O)CH 3 , CH 2 NHC(O)O(CH 3 ), difluoromethoxy, cyanomethyl, aminomethyl, (hydroxyl)methyl, amino, CH 2 (3,3-dimethylazetidin-1-yl), CH 2 NH-(3-methoxycyclobutyl), CH 2 NHCH 2 -(1-methylcyclopropyl), and morpholinyl.
10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently selected from methyl, trifluoromethyl, cyclopropyl substituted with methanamine, fluoro, chloro, hydroxy, methoxy, and ethoxy.
11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently methoxy or fluoro.
12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy A is selected from 2-fluoro-6-methoxyphenyl, 2,6-difluorophenyl, 2,6-dimethylphenyl, 2,4,6-trifluorophenyl, 2-chloro-6-fluorophenyl, 1-hydroxy-3,5-difluoro-phen-4-yl, 2-fluoro-6-methylphenyl, 2-ethoxy-6-fluorophenyl, 2-chloro-6-methoxyphenyl, and 2-fluoro-6-(trifluoromethyl)phenyl.
13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is selected from 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl, wherein each 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 .
14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is thiazolyl, isoxazolyl, piperazinonyl, 1,2,3,4-tetrahydroisoquinolinyl, piperazinyl, phenyl, pyrazolyl, pyridinyl, imidazolyl, or pyrimidinyl; each is optionally with 1, 2, 3 or 4 substituents independently selected from R 10 .
15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is thiazolyl, isoxazolyl, piperazinonyl, 1,2,3,4-tetrahydroisoquinolinyl, piperazinyl, or phenyl; each is optionally with 1, 2, 3 or 4 substituents independently selected from R 10 .
16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 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 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 said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 .
17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , NR c1 R d1 , and NR c1 C(O)R b1 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 .
18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a1 , C(O)NR c1 R d1 , and NR c1 R d1 ; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 11 .
19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, and OR a1 ; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 11 .
20. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, OR a3 , SR 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 , and NR c3 C(O)OR a3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 .
21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , and NR c3 C(O)R b3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 .
22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently selected from C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a3 , C(O)OR a3 ; wherein said C 1-6 alkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 12 .
23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from methyl, bromo, fluoro, CN, ethyl, methoxy, 4-morpholinyl, 3-oxopiperazin-1-yl, 4-methylpiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, 4-ethylpiperazin-1-yl, 3-oxo-4-(2,2,2-trifluoroethyl)piperazin-1-yl, 4-(methylsulfonyl)piperazin-1-yl, piperazin-1-yl, 4-isopropylpiperazin-1-yl, 4-cyclopropyl-3-oxopiperazin-1-yl, 4-(methylsulfonyl)piperazin-1-yl, 4-bromo-phenyl, 4-cyanophenyl, 4-pyridyl, methylaminocarbonyl, isopropylaminocarbonyl, 3-hydroxypyrrolidin-1-yl, 3-methoxypiperidin-1-yl, 1-methylpiperidin-4-yl, ethylmethylamino, cyclopropyl, 2-cyanophenyl, tetrahydro-2H-pyran-4-yl, azetidin-3-yl, hydroxyethyl, 4-methoxypiperidin-1-yl, 3-fluoropyrrolidin-1-yl, 4-methylcarbonylpiperazin-1-yl, and 4-hydroxypiperidin-1-yl, 4-methoxycarbonylpiperazin-1-yl, amino, 2-hydroxypropylamino, (1-methyl-1H-pyrazol-5-yl)methylamino, and 3-cyanocyclopentylamino.
24. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from methyl, bromo, fluoro, CN, ethyl, methoxy, 4-morpholinyl, 3-oxopiperazin-1-yl, 4-methylpiperazin-1-yl, 4-methyl-3-oxopiperazin-1-yl, 4-ethylpiperazin-1-yl, 3-oxo-4-(2,2,2-trifluoroethyl)piperazin-1-yl, 4-(methylsulfonyl)piperazin-1-yl, piperazin-1-yl, 4-isopropylpiperazin-1-yl, 4-cyclopropyl-3-oxopiperazin-1-yl, 4-(methylsulfonyl)piperazin-1-yl, 4-bromo-phenyl, 4-cyanophenyl, and 4-pyridyl.
25. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, halo, 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 , and NR c7 C(O)OR a7 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 30 .
26. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, 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 , and NR c7 C(O)OR a7 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 30 .
27. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, and OR a7 .
28. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and halo.
29. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is H.
30. The compound of claim 1 having Formula IV:
wherein n is 1, 2, 3, or 4; or a pharmaceutically acceptable salt thereof.
31. The compound of claim 1 having Formula Va:
wherein n is 1, 2, 3, or 4; or a pharmaceutically acceptable salt thereof.
32. The compound of claim 1 having Formula Val:
wherein n is 1, 2, 3, or 4; or a pharmaceutically acceptable salt thereof.
33. The compound of claim 30 , or a pharmaceutically acceptable salt thereof, wherein n is 3.
34. The compound of claim 30 , or a pharmaceutically acceptable salt thereof, wherein n is 2.
35. The compound of claim 30 , or a pharmaceutically acceptable salt thereof, wherein each R 20 is independently fluoro, methyl, trifluoromethyl, CH 2 NHCH 3 , CH 2 NH(i-propyl), CH 2 -azetidinyl, CH 2 NH(CH 2 )CH 3 , or CH(CH 3 )(NHCH 3 ).
36. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl, wherein each 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ;
Cy A is C 6-10 aryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 20 ;
R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, OR a7 , SR 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 , NR c7 C(O)OR a7 , 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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 30 ;
each R 10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 6-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, NO 2 , 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(═NOR a1 )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 said C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 6-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;
or two R 10 substituents taken together with the carbon atom to which they are attached form a spiro 3-7-membered heterocycloalkyl ring, or a spiro C 3-6 cycloalkyl ring; wherein each spiro 3-7-membered heterocycloalkyl ring has at least one ring-forming carbon atom and 1, 2 or 3, ring-forming heteroatoms independently selected from N, O, and S; wherein a ring-forming carbon atom of each spiro 3-7-membered heterocycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the spiro 3-7-membered heterocycloalkyl ring and spiro C 3-6 cycloalkyl ring are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 11 ;
each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, OR a3 , SR 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 , NR c3 C(O)OR a3 , 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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;
each R 12 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, CN, OR a5 , SR 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 , NR c5 C(O)OR a5 , 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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, NO 2 , 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(═NOR a2 )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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;
or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of the fused C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the fused C 3-7 cycloalkyl ring is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 ;
each R 21 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene, 5-10 membered heteroaryl-C 1-3 alkylene, halo, CN, OR a4 , SR 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 , NR c4 C(O)OR a4 , 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, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl-C 1-3 alkylene, 4-10 membered heterocycloalkyl-C 1-3 alkylene, C 6-10 aryl-C 1-3 alkylene and 5-10 membered heteroaryl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 22 ;
or two R 21 substituents taken together with the carbon atom to which they are attached form a spiro C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of the spiro C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the spiro C 3-7 cycloalkyl ring is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 22 ;
each R 22 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, CN, OR a6 , SR 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 , NR c6 C(O)OR a6 , 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 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R 30 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, CN, OR a8 , SR a8 , C(O)R b8 , C(O)NR c8 R d8 , C(O)OR a8 , NR c8 R d8 , NR c8 C(O)R b8 , NR c8 C(O)OR a8 , NR c8 S(O)R b8 , NR c8 S(O) 2 R b8 , NR c8 S(O) 2 NR c8 R d8 , S(O)R b8 , S(O)NR c8 R d8 , S(O) 2 R b8 , and S(O) 2 NR c8 R d8 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R a1 , R c1 and R d1 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;
or any R c1 and R d1 attached to the same N atom, 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, 3 or 4 substituents independently selected from R 11 ;
each R b1 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;
each R e1 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;
each R a2 , R c2 and R d2 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;
or any R c2 and R d2 attached to the same N atom, 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, 3 or 4 substituents independently selected from R 21 ;
each R b2 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;
each R e2 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkylsulfonyl, C 1-6 alkylcarbonyl, C 1-6 alkylaminosulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, aminosulfonyl, C 1-6 alkylaminosulfonyl and di(C 1-6 alkyl)aminosulfonyl;
each R a3 , R c3 and R d3 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;
or any R c3 and R d3 attached to the same N atom, 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 R 12 ;
each R b3 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;
each R a4 , R c4 and R d4 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 22 ;
or any R c4 and R d4 attached to the same N atom, 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 R 22 ;
each R b4 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 22 ;
each R a5 , R c5 and R d5 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R b5 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R a6 , R c6 and R d6 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R b6 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R a7 , R c7 , and R d7 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 30 ;
or any R c7 and R d7 attached to the same N atom, 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 R 30 ;
each R b7 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl;
each R a8 , R c8 and R d8 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
or any R c8 and R d8 attached to the same N atom, 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 R g ;
each R b8 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ; and
each R g is independently selected from OH, NO 2 , CN, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-2 alkylene, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-3 alkoxy-C 1-3 alkyl, C 1-3 alkoxy-C 1-3 alkoxy, HO—C 1-3 alkoxy, HO—C 1-3 alkyl, cyano-C 1-3 alkyl, H 2 N-C 1-3 alkyl, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, carboxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, aminosulfonyl, C 1-6 alkylaminosulfonyl, di(C 1-6 alkyl)aminosulfonyl, aminosulfonylamino, C 1-6 alkylaminosulfonylamino, di(C 1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6 alkylaminocarbonylamino, and di(C 1-6 alkyl)aminocarbonylamino.
37. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl, wherein each 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ;
Cy A is C 6-10 aryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 20 ;
R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, OR a7 , SR 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 , NR c7 C(O)OR a7 , 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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 30 ;
each R 10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, NO 2 , 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 , and NR c1 C(O)OR a1 ; wherein said C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;
each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a3 , SR 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 , NR c3 C(O)OR a3 , S(O)R b3 , S(O)NR C3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;
each R 12 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, CN, OR a5 , SR 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 , NR c5 C(O)OR a5 , 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 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R g ;
each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl-C 1-3 alkylene, halo, CN, NO 2 , 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 , and NR c2 C(O)OR a2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;
or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of the fused C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the fused C 3-7 cycloalkyl ring is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 ;
each R 21 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a4 , SR 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 , and NR c4 C(O)OR a4 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 22 ;
each R 22 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, CN, OR a6 , SR 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 , and NR c6 C(O)OR a6 ; wherein said C 1 -6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and 5-6 membered heteroaryl are each optionally substituted with 1 substituents independently selected from R g ;
each R 30 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl;
each R a1 , R c1 and R d1 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and C 3-10 cycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-10 cycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 11 ;
each R b1 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;
each R a2 , R c2 and R d2 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and 4-10 membered heterocycloalkyl; said C 1-6 alkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 21 ;
or any R c2 and R d2 attached to the same N atom, 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, 3 or 4 substituents independently selected from R 21 ;
each R b2 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 21 ;
each R a3 , R c3 and R d3 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl;
each R b3 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and phenyl;
each R a4 , R c4 and R d4 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 22 ;
or any R c4 and R d4 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
each R b4 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, and phenyl;
each R a5 , R c5 and R d5 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl;
each R b5 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl;
each R a6 , R c6 and R d6 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl;
each R b6 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl;
each R a7 , R c7 , and R d7 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 30 ;
each R b7 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 30 ; and
each R g is independently selected from OH, NO 2 , CN, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-2 alkylene, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-3 alkoxy-C 1-3 alkyl, C 1-3 alkoxy-C 1-3 alkoxy, HO—C 1-3 alkoxy, HO—C 1-3 alkyl, cyano-C 1-3 alkyl, H 2 N-C 1-3 alkyl, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, thio, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 alkyl)carbamyl, carboxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonylamino, aminosulfonyl, C 1-6 alkylaminosulfonyl, di(C 1-6 alkyl)aminosulfonyl, aminosulfonylamino, C 1-6 alkylaminosulfonylamino, di(C 1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-6 alkylaminocarbonylamino, and di(C 1-6 alkyl)aminocarbonylamino.
38. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl, wherein each 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 10 ;
Cy A is C 6-10 aryl optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 20 ;
R 2 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, and OR a7 ;
each R 10 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a1 , C(O)NR c1 R d1 , and NR c1 R d1 ; wherein said C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;
each R 11 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a3 , C(O)OR a3 , C(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;
each R 12 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, and CN;
each R 20 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl-C 1-3 alkylene, halo, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , 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 , and NR c2 C(O)NR c2 R d2 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl-C 1-3 alkylene are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 21 ;
or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused C 3-7 cycloalkyl ring; wherein a ring-forming carbon atom of the fused C 3-7 cycloalkyl ring is optionally substituted by oxo to form a carbonyl group; and wherein the fused C 3-7 cycloalkyl ring is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 21 ;
each R 21 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a4 , NR c4 R d4 , NR c4 C(O)R b4 , and NR c4 C(O)OR a4 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 22 ;
each R 22 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, phenyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, CN, OR 6a , NR c6 R d6 , and NR c6 C(O)R b6 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R g ;
each R a1 , R c1 , and R d1 is independently selected from H, C 1-6 alkyl, and C 3-10 cycloalkyl; wherein said C 1-6 alkyl and C 3-10 cycloalkyl, are each optionally substituted with 1 or 2 substituents independently selected from R 11 ;
each R a2 , R c2 and R d2 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and 4-10 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 21 ;
or any R c2 and R d2 attached to the same N atom, 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, 3 or 4 substituents independently selected from R 21 ;
each R b2 is independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 21 ;
each R a3 , R c3 and R d3 , is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl;
each R b3 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, and phenyl;
each R a4 , R c4 and R d4 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 22 ;
or any R c4 and R d4 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
each R b4 is independently selected from C 1-6 alkyl;
each R a6 is independently selected from H and C 1-6 alkyl;
each R c6 and R d6 is independently selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl and C 1-6 haloalkyl;
each R b6 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 1-6 haloalkyl;
each R a7 is independently selected from H and C 1-6 alkyl; and
each R g is independently selected from C 1-6 alkyl.
39. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl, wherein each 4-10 membered heterocycloalkyl and 5-10 membered heteroaryl has at least one ring-forming carbon atom and 1, 2, 3, or 4 ring-forming heteroatoms independently selected from N, O, and S; wherein the N and S are optionally oxidized; wherein a ring-forming carbon atom of 5-10 membered heteroaryl and 4-10 membered heterocycloalkyl is optionally substituted by oxo to form a carbonyl group; and wherein the 4-10 membered heterocycloalkyl, C 6-10 aryl and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 10 ;
Cy A is C 6-10 aryl optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 20 ;
R 2 is H, halo, or OR a7 ;
each R 10 is independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a1 , C(O)NR c1 R d1 , and NR c1 R d1 ; wherein said C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 1 ;
each R 11 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, halo, CN, OR a3 , C(O)OR a3 , and S(O) 2 R b3 ; wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 12 ;
each R 12 is C 1-6 alkyl, halo, or CN;
each R 20 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, 4-10 membered heterocycloalkyl-C 1-3 alkylene, halo, OR a2 , C(O)R b2 , C(O)NR c2 R d2 , 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 , and NR c2 C(O)NR c2 R d2 ; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 4-10 membered heterocycloalkyl-C 1-3 alkylene are each optionally substituted with 1 or 2 substituents independently selected from R 21 ;
or two adjacent R 20 substituents on the Cy A ring, taken together with the atoms to which they are attached, form a fused C 3-7 cycloalkyl ring; and wherein the fused C 3-7 cycloalkyl ring is optionally substituted with 1 or 2 substituents independently selected from R 21 ;
each R 21 is C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, halo, CN, OR a4 , NR c4 R d4 , NR c4 C(O)R b4 , and NR c4 C(O)OR a4 ; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 22 ;
each R 22 is independently selected from C 1-6 alkyl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, CN, OR a6 and NR c6 R d6 ; wherein said C 1-6 alkyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R g ;
each R a1 , R c1 and R d1 is independently selected from H, C 1-6 alkyl, and C 3-10 cycloalkyl; wherein said C 1-6 alkyl and C 3-10 cyclo membered alkyl, are each optionally substituted with 1 or 2 substituents independently selected from R 11 ;
each R a2 , R c2 and R d2 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, and 4-10 membered heterocycloalkyl; wherein said C 1-6 alkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 21 ;
or any R c2 and R d2 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from R 21 ;
each R b2 is independently selected from C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 21 ;
each R a3 is independently selected from H and C 1-6 alkyl;
each R b3 is C 1-6 alkyl;
each R a4 , R c4 and R d4 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl; wherein said C 1-6 alkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl and 4-7 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 22 ;
or any R c4 and R d4 attached to the same N atom, together with the N atom to which they are attached, form a 4-, 5-, 6- or 7-membered heterocycloalkyl group;
each R b4 is independently selected from C 1-6 alkyl;
each R a6 is independently selected from H and C 1-6 alkyl;
each R c6 and R d6 is H;
each R a7 is independently selected from H and C 1-6 alkyl; and
each R g is independently selected from C 1-6 alkyl.
40. The compound of claim 1 selected from
4-(5-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)thiazol-2-yl)morpholine;
5-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-3-methylisoxazole;
5-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-methylthiazole;
1-(4-Bromophenyl)-4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)piperazin-2-one;
2-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile;
4-(4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)piperazin-1-yl)benzonitrile;
5-(2-Fluoro-6-methoxyphenyl)-3-(4-(pyridin-4-yl)piperazin-1-yl)-1H-pyrazolo[3,4-c]pyridine;
1-[1-(3-Fluoro-5-{3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazolo[3,4-c]pyridin-5-yl}phenyl)cyclopropyl]methanamine;
5-(2-Fluoro-6-methoxyphenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine;
5-(2,6-Difluorophenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine;
5-(2,6-Dimethylphenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine;
3-(4-(4-Methylpiperazin-1-yl)phenyl)-5-(2,4,6-trifluorophenyl)-1H-pyrazolo[3,4-c]pyridine;
5-(2-Chloro-6-fluorophenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine;
3,5-Difluoro-4-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenol;
5-(2-Fluoro-6-methylphenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine;
5-(2-Chloro-6-(trifluoromethyl)phenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine;
5-(2-Ethoxy-6-fluorophenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine;
5-(2-Chloro-6-methoxyphenyl)-3-(4-(4a-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine; and
5-(2-Fluoro-6-(trifluoromethyl)phenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine;
or a pharmaceutically acceptable salt thereof.
41. The compound of claim 1 selected from:
3,5-Difluoro-N-(2-methoxyethyl)-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzamide,
(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)(3-methoxyazetidin-1-yl)methanone,
N-(2,4-Difluoro-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)cyclobutanecarboxamide,
N-(2,4-Difluoro-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-2-phenylacetamide,
2,4-Difluoro-N-methyl-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)aniline,
2,4-Difluoro-N,N-dimethyl-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)aniline,
3,5-Difluoro-N,N-dimethyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)aniline,
N-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-2-(pyrrolidin-1-yl)acetamide,
N-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide,
2-Cyclopentyl-N-(3,5-difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetamide,
N-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-2-(pyridin-3-yl)acetamide,
2-(7-Azabicyclo[2.2.1]heptan-7-yl)-N-(3,5-difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetamide,
N-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-2-(7-oxa-2-azaspiro[3.5]nonan-2-yl)acetamide,
N-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-2-(pyrrolidin-1-yl)propanamide,
1-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-3-(2-methoxyethyl)urea,
2-(Azetidin-1-yl)-N-(3-(difluoromethoxy)-5-fluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetamide,
N-(3-Chloro-5-fluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-2-(pyrrolidin-1-yl)acetamide,
N-(3-Fluoro-5-methoxy-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-2-(pyrrolidin-1-yl)acetamide,
2-(3,3-Dimethylazetidin-1-yl)-N-(3-fluoro-5-methoxy-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetamide,
1-Methylpiperidin-4-yl 3-fluoro-5-methoxy-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenylcarbamate,
2-(Azetidin-1-yl)-N-(2,3,5-trifluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetamide,
N-(3-Chloro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-2-(dimethylamino)acetamide,
2-((1R,4S)-2-Azabicyclo[2.2.1]heptan-2-yl)-N-(3-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetamide,
N-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-2-(pyrrolidin-1-yl)acetamide,
2-(Dimethylamino)-N-(3-fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetamide,
2-(7-Azabicyclo[2.2.1] heptan-7-yl)-N-(3-fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetamide,
2-((1R,4S)-2-Azabicyclo[2.2.1]heptan-2-yl)-N-(3-fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetamide,
3-(Dimethylamino)-N-(3-fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)propanamide,
2-Cyano-N-(3-fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetamide,
N-Methyl-1-(2-methyl-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)methanamine,
N-Methyl-1-(4-methyl-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)methanamine,
N-Methyl-1-(3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2-(trifluoromethyl)phenyl)methanamine,
5-(3-(Azetidin-l-ylmethyl)-2-(trifluoromethyl)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
N-(3-(3-(1-Methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2-(trifluoromethyl)benzyl)tetrahydro-2H-pyran-4-amine,
N-(3-(3-(1-Methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2-(trifluoromethyl)benzyl)propan-2-amine,
1-(4-Fluoro-2-methyl-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
N-(4-Fluoro-2-methyl-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)propan-2-amine,
5-(3-(Azetidin-l-ylmethyl)-6-fluoro-2-methylphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
3-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-isopropylcyclobutanamine,
2-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylethanamine,
2-(2,4-Difluoro-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylethanamine,
N-(2,4-Difluoro-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenethyl)tetrahydro-2H-pyran-4-amine,
N-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenethyl)-1-isopropylazetidin-3-amine,
2-Fluoro-4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-N-methylbenzamide,
5-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-N-methylpicolinamide,
4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-2-methoxy-N-methylbenzamide,
4-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-N,2-dimethylbenzamide,
1-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-N-isopropyl-1H-imidazole-4-carboxamide,
1-(5-(2-Fluoro-6-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-N-methyl-1H-imidazole-4-carboxamide,
5-(4-(Azetidin-2-ylmethoxy)-2,6-difluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
5-(2,6-Difluoro-4-(tetrahydro-2H-pyran-4-yloxy)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
5-(2,6-Difluoro-4-(pyridin-4-ylmethoxy)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl dimethylcarbamate,
3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl morpholine-4-carboxylate,
N-Methyl-1-(3-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)methanamine,
N-Methyl-1-(4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-3-(trifluoromethyl)phenyl)methanamine,
1-(5-(5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)pyrrolidin-3-ol,
1-(3-Fluoro-4-(3-(6-(3-methoxypiperidin-1-yl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-5-methylphenyl)-N-methylmethanamine,
5-(2-Fluoro-6-methoxyphenyl)-3-(6-(1-methylpiperidin-4-yl)pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridine,
1-(3-Fluoro-5-methyl-4-(3-(6-morpholinopyridin-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
N-Ethyl-6-(5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-N-methylpyridin-2-amine,
1-(3-Fluoro-4-(3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-5-(trifluoromethyl)phenyl)-N-methylmethanamine,
1-(4-(3-(6-Cyclopropylpyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-3-fluoro-5-(trifluoromethyl)phenyl)-N-methylmethanamine,
1-(3-Fluoro-4-(3-(6-morpholinopyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-5-(trifluoromethyl)phenyl)-N-methylmethanamine,
1-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
N-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)propan-2-amine,
N-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)pyridin-2-amine,
N-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)-1-methyl-1H-pyrazol-3-amine,
2-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzylamino)ethanol,
1-(2,4-Difluoro-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
N-(2,4-Difluoro-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)propan-2-amine,
N-(2,4-Difluoro-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)cyclopropanamine,
5-(2,6-Difluoro-3-((3-methoxypiperidin-1-yl)methyl)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
1-(3-Fluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-5-(trifluoromethyl)phenyl)-N-methylmethanamine,
1-(3-Fluoro-4-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-5-(trifluoromethyl)phenyl)-N-methylmethanamine,
1-(4-(3-(1-Ethyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-3-fluoro-5-methylphenyl)-N-methylmethanamine,
1-(4-(3-(1-Cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-3-fluoro-5-methylphenyl)-N-methylmethanamine,
2-(4-(5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-pyrazol-1-yl)benzonitrile,
1-(3-Fluoro-5-methyl-4-(3-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
1-(3,5-Difluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylcyclopropanamine,
1-(4-Fluoro-2-methoxy-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
N-(4-Fluoro-2-methoxy-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)ethanamine,
2-(4-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-pyrazol-1-yl)benzonitrile,
1-(4-(3-(1-(Azetidin-3-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-3,5-difluorophenyl)-N-methylmethanamine,
1-(3,5-Difluoro-4-(3-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
2-(4-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-1H-pyrazol-1-yl)ethanol,
1-(3,5-Difluoro-4-(3-(4-methoxyphenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
1-(5-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)piperidin-4-ol,
1-(3,5-Difluoro-4-(3-(5-(3-fluoropyrrolidin-1-yl)pyridin-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
1-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
4-(5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-N-methylbenzamide,
4-(5-(2-Fluoro-6-methyl-4-(pyrrolidin-2-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-N-methylbenzamide,
5-(2-Fluoro-6-methyl-4-(pyrrolidin-2-yl)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
5-(2-Fluoro-6-methyl-4-(1-methylpyrrolidin-2-yl)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
5-(2-Fluoro-6-methyl-4-(piperidin-2-yl)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine (enantiomer 1),
5-(2-Fluoro-6-methyl-4-(piperidin-2-yl)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine (enantiomer 2),
N-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)ethanamine,
N-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)cyclopropanamine,
N-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)propan-2-amine,
2,2,2-Trifluoro-N-(3-fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)ethanamine,
2-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzylamino)ethanol,
3-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzylamino)cyclobutanol,
5-(4-(Azetidin-1-ylmethyl)-2-fluoro-6-methylphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
1-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)pyrrolidin-3-ol,
5-(2-Fluoro-4-((3-methoxyazetidin-1-yl)methyl)-6-methylphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
N-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)-1-(1-methyl-1H-imidazol-4-yl)methanamine,
N-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)-1-(oxazol-4-yl)methanamine,
2-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzylamino)acetonitrile,
1-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylethanamine,
N-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)acetamide,
Methyl 3-fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzylcarbamate,
1-(4-(6-(5-(2-(Difluoromethoxy)-6-fluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-3-yl)piperazin-1-yl)ethanone,
2-(3-Fluoro-2-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetonitrile,
(3-Fluoro-2-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)methanamine,
(3-Fluoro-2-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)methanol,
4,6-Difluoro-N-methyl-5-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2,3-dihydro-1H-inden-1-amine,
4,6-Difluoro-N-methyl-5-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2,3-dihydro-1H-inden-1-amine,
6,8-Difluoro-N-methyl-7-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-amine,
6,8-Difluoro-N-methyl-7-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-2-amine,
4-(5-(1,3-Difluoro-5-(methylamino)-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-N-methylbenzamide,
5,7-Difluoro-N-methyl-6-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-amine,
5,7-Difluoro-6-(3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-amine,
4-(5-(4,6-Difluoro-3-(methylamino)-2,3-dihydro-1H-inden-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-N-methylbenzamide,
5,7-Difluoro-N-methyl-6-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2,3-dihydro-1H-inden-1-amine,
5-Fluoro-7-methoxy-6-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2,3-dihydro-1H-inden-1-amine,
5-Fluoro-7-methoxy-6-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2,3-dihydro-1H-inden-1-amine,
5-(5-(2-Fluoro-5-(methylamino)-5,6,7,8-tetrahydronaphthalen-1-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)-N-methylpicolinamide,
6-Fluoro-N-methyl-5-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-amine,
6-Fluoro-5-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-amine,
2-(3,5-Difluoro-4-(3-(2-(4-methylpiperazin-1-yl)pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)acetonitrile,
5,7-Difluoro-6-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2,3-dihydro-1H-inden-1-ol,
5,7-Difluoro-6-(3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2,3-dihydro-1H-inden-1-ol,
6,8-Difluoro-7-(4-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-N-methyl-1,2,3,4-tetrahydronaphthalen-2-amine,
1-(3,5-Difluoro-4-(4-methoxy-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
5,7-Difluoro-6-(4-fluoro-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2,3-dihydro-1H-inden-1-amine,
1-(3,5-Difluoro-4-(3-(2-(4-methylpiperazin-1-yl)pyrimidin-5-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
1-(5-(5-(2,6-Difluoro-4-((methylamino)methyl)phenyl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyrimidin-2-yl)piperidin-4-ol,
1-(3,5-Difluoro-4-(3-(5-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
4-Fluoro-N,6-dimethyl-5-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2,3-dihydro-1H-inden-1-amine,
5-(3-((3,3-Dimethylazetidin-1-yl)methyl)-6-fluoro-2-methylphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
trans-N-(4-Fluoro-2-methyl-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)-3-methoxycyclobutanamine,
N-(4-Fluoro-2-methyl-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)-3,3-dimethylcyclobutanamine,
N-(4-Fluoro-2-methyl-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)-1-(1-methylcyclopropyl)methanamine,
1-(4-Fluoro-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2-(trifluoromethyl)phenyl)-N-methylmethanamine,
5-(2-Fluoro-4-(pyrrolidin-2-yl)-6-(trifluoromethyl)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridine,
1-(4-(3-(1-Cyclopropyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-3-fluoro-5-methylphenyl)-N-methylethanamine,
3-(1-Ethyl-1H-pyrazol-4-yl)-5-(2-fluoro-6-methyl-4-(piperidin-2-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine,
3-(1-Cyclopropyl-1H-pyrazol-4-yl)-5-(2-fluoro-6-methyl-4-(piperidin-2-yl)phenyl)-1H-pyrazolo[3,4-c]pyridine,
3-(3-Fluoro-5-methyl-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)morpholine,
1-(3-(Difluoromethyl)-5-fluoro-4-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)phenyl)-N-methylmethanamine,
N-(4-Fluoro-2-methyl-3-(3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)benzyl)ethanamine,
N-(3-(3-(1-Methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-2-(trifluoromethyl)benzyl)ethanamine,
6-Fluoro-N-methyl-5-(3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-amine, and
6-Fluoro-5-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-amine,
or a pharmaceutically acceptable salt thereof.
42. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.