IP Library › Granted Patent US 11,939,331

Granted Patent B2

US 11,939,331 · App. 17/835,331 · Granted Mar 26, 2024

Tricyclic heterocycles as FGFR inhibitors

Inventors: Xin Li (Claymont, DE); Evan Styduhar (Claymont, DE); Robert Swyka (Wilmington, DE); Oleg Vechorkin (Wilmington, DE); Wenqing Yao (Chadds Ford, PA)

Assignee: Incyte Corporation

C07D471/14 A61K31/4375 A61K31/439 A61K31/496 A61K31/506 A61K31/5377 A61K31/541 A61P35/00 C07D519/00

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Quick Facts

Patent No.: US 11,939,331
App. No.: 17/835,331
Granted: Mar 26, 2024
Kind: B2

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Abstract

The present disclosure relates to tricyclic heterocycles, and pharmaceutical compositions of the same, that are inhibitors of the FGFR enzyme and are useful in the treatment of FGFR-associated diseases such as cancer.

Claims (224)

1. A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 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, D, 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 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 10 ;

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, D, 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 20 ;

R 3 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, D, CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 C(O)NR c3 R d3 , C(═NR e3 )R b3 , C(═NOR a3 )R b3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ; 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 ;

R 4 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, D, CN, NO 2 , OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)OR a4 , NR c4 C(O)NR c4 R d4 , C(═NR e4 )R b4 , C(═NOR a4 )R b4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 , NR c4 S(O)R b4 , NR c4 S(O) 2 R b4 , NR c4 S(O) 2 NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , and S(O) 2 NR c4 R d4 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, 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 40 ;

R 5 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, D, CN, NO 2 , OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)OR a5 , NR c5 C(O)NR c5 R d5 , (═NR e5 )R b5 , C(═NOR a5 )R b5 , (═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , NR c5 S(O)R b5, NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , and S(O) 2 NR c5 R d5 ; 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 50 ;

Z is N or CR 6 ;

R 6 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, D, CN, NO 2 , OR a6 , SR a6 , CO)R b6 , C(O)NR c6 R d6 , C(O)OR a6 , OC(O)R b6 , OC(O)NR c6 R d6 , NR c6 R d6 , NR c6 C(O)R b6 , NR c6 C(O)OR a6 , NR c6 C(O)NR c6 R d6 , C(═NR e6 )R b6 , C(═NOR a6 )R b6 , C(═NR e6 )NR c6 R d6 , NR c6 C(═NR e6 )NR c6 R d6 , NR c6 S(O)R b6 , NR c6 S(O) 2 R b6 , NR c6 S(O) 2 NR c6 R d6 , S(O)R b6 , S(O)NR c6 R d6 , S(O) 2 R b6 , and S(O) 2 NR c6 R d6 ; wherein said C 1-6 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 60 ;

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, D, CN, NO 2 , OR a10 , SR a10 , C(O)R b10 , C(O)NR c10 R d10 , C(O)OR a10 , OC(O)R b10 , OC(O)NR c10 R d10 , NR c10 R d10 NR c10 C(O)R b10 , NR c10 C(O)OR a10 , NR c10 C(O)NR c10 R d10 , C(═NR e10 )R b10 , C(═NOR a10 )R b10 , C(═NR e10 )NR c10 R d10 , NR c10 C(═NR e10 )NR c10 R d10 , NR c10 S(O)R b10 , NR c10 S(O) 2 R b10 , NR c10 S(O) 2 NR c10 R d10 , S(O)R b10 , S(O)NR c10 R d10 , S(O) 2 R b10 , and S(O) 2 NR c10 R d10 ; 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 ;

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, D, CN, OR a11 , SR a11 , (O)R b11 , C(O)NR c11 R d11 , C(O)OR a11 , NR c11 R d11 , NR c11 C(O)R b11 , C(O)OR a11 , NR c11 C(O)NR c11 R d11 , NR c11 S(O)R b11 NR c11 S(O) 2 R b11 , NR c11 S(O) 2 NR c11 R d11 , S(O)R b11 , S(O)NR c11 R d11 , S(O) 2 R b11 , and S(O) 2 NR c11 R d11 ; 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, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a12 , SR a12 , C(O)R b12 , C(O)NR c12 R d12 , C(O)OR a12 , NR c12 R d12 , NR c12 C(O)R b12 , NR c12 C(O)OR a12 , NR c12 C(O)NR c12 R d12 , NR c12 S(O)R b12 , NR c12 S(O) 2 R b12 , NR c12 S(O) 2 NR c12 R d12 , S(O)R b12 , S(O)NR c12 R d12 , S(O) 2 R b12 , and S(O) 2 NR c12 R d12 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 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 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, D, CN, NO 2 , OR a20 , SR a20 , C(O)R b20 , C(O)NR c20 R d20 , C(O)OR a20 , OC(O)R b20 , OC(O)NR c20 R d20 , NR c20 R d20 , NR c20 , C(O)R b20 , NR c20 C(O)R a20 , NR c20 C(O)NR c20 R d20 , C(═NR e20 )R b20 , C(═NOR a20 )R b20 , C(═NR e20 )NR c20 R d20 , NR c20 C(═NR e20 )NR c20 R d20 , NR c20 S(O)R b20 , NR c20 S(O) 2 R b20 , NR c20 S(O) 2 NR c20 R d20 , S(O)R b20 , S(O)NR c20 R d20 , S(O) 2 R b20 , and S(O) 2 NR c20 R d20 ; 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 ;

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, D, CN, OR a21 , SR a21 , C(O)R b21 , C(O)NR c21 R d21 , C(O)OR a21 , NR c21 R d21 , NR c21 C(O)R b21 , NR c21 C(O)OR a21 , NR c21 C(O)NR c21 R d21 , NR c21 S(O)R b21 , NR c21 S(O) 2 R b21 , NR c21 S(O) 2 NR c21 R d21 , S(O)R b21 , S(O)NR c21 R d21 , S(O) 2 R b21 , and S(O) 2 NR c21 R d21 , 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 ;

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, D, CN, OR a22 , SR a22 , C(O)R b22 , C(O)NR c22 R d22 , C(O)OR a22 , NR c22 R d22 , NR c22 C(O)R b22 , NR c22 C(O)OR a22 , NR c22 C(O)NR c22 R d22 , NR c22 S(O)R b22 , NR c22 S(O) 2 R b22 , NR c22 S(O) 2 NR c22 R d22 , S(O)R b22 , S(O)NR c22 R d22 , S(O) 2 R b22 , and S(O) 2 NR c22 R d22 ; 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 3-10 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, D, CN, NO 2 , OR a30 , SR a30 , C(O)R b30 , C(O)NR c30 R d30 , C(O)OR a30 , OC(O)R b30 , OC(O)NR c30 R c30 , NR c30 R c30 , NR c30 C(O)R b30 , NR c30 C(O)R a30 , NR c30 C(O)NR c30 R d30 , C(═NR e30 )R b30 , C(═NOR a30 )R b30 , C(═NR e30 )NR c30 R d30 , NR c30 C(═NR e30 )NR c30 R d30 , NR c30 S(O)R b30 , NR c30 S(O) 2 R b30 , NR c30 S(O) 2 NR c30 R d30 , S(O)R b30 , S(O)NR c30 R d30 , S(O) 2 R b30 , and S(O) 2 NR c30 R d30 ; 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 31 ;

each R 31 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, D, CN, OR a31 , SR a31 , C(O)R b31 , C(O)NR c31 R d31 , C(O)OR a31 , NR c31 R d31, NR c31 C(O)R b31 , NR c31 C(O)OR a31 , NR c31 C(O)NR c31 R d31 , NR c31 S(O)R b31 , NR c31 S(O) 2 R b31 , NR c31 S(O) 2 NR c31 R d31 , S(O)R b31 , S(O)NR c31 R d31 , S(O) 2 R b31 , and S(O) 2 NR c31 R d31 ; 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 32 ;

each R 32 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, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a32 , SR a32 , C(O)R b32 , C(O)NR c32 R d32 , C(O)OR a32 , NR c32 R d32 , NR c32 C(O)R b32 , NR c32 OR a32 , NR c32 C(O)NR c32 R d32 , NR c32 S(O)R b32 , NR c32 S(O) 2 R b32 , NR c32 S(O) 2 NR c32 R d32 , S(O)R b32 , S(O)NR c32 R d32 , S(O) 2 R b32 , and S(O) 2 NR c32 R d32 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 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 40 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, D, CN, NO 2 , OR a40 , SR a40 , C(O)R b40 , C(O)NR c40 R d40 , C(O)OR a40 , OC(O)R b40 , OC(O)NR c40 R d40 , NR c40 R d40 , NR c40 C(O)R b40 , NR c40 C(O)OR a40 , NR c40 C(O)NR c40 R d40 , C(═NR e40 )R b40 , C(═NOR a40 )R b40 , C(═NR e40 )NR c40 R d40 , NR c40 C(═NR e40 )NR c40 R d40 , NR c40 S(O)R b40 , NR c40 S(O) 2 R b40 , NR c40 S(O) 2 NR c40 R d40 , S(O)R b40 , S(O)NR c40 R d40 , S(O) 2 R b40 , and S(O) 2 NR c40 R d40 , 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 41 ;

each R 41 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, D, CN, OR a41 , SR a41 , (O)R b41 , C(O)NR c41 R d41 , C(O)OR a41 , NR c41 R d41 , NR c41 C(O)R b41 , NR c41 C(O)O R a41 , NR c41 C(O)NR c41 R d41 , NR c41 S(O)R b41 , NR c41 S(O) 2 R b41 , NR c41 S(O) 2 NR c41 R d41 , S(O)R b41 , S(O)NR c41 R d41 , S(O) 2 R b41 , and S(O) 2 NR c41 R d41 , 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 42 ;

each R 42 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, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a42 , SR a42 , C(O)R b42 , C(O)NR c42 R d42 , C(O)OR a42 , NR c42 R d42 , NR c42 C(O)R b42 , NR c42 C(O)OR a42 , NR c42 C(O)NR c42 R d42 , NR c42 S(O)R b42 , NR c42 S(O) 2 R b42 , NR c42 S(O) 2 NR c42 R d42 , S(O)R b42 , S(O)NR c42 R d42 , S(O) 2 R b42 , and S(O) 2 NR c42 R d42 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 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 50 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, D, CN, NO 2 , OR a50 , SR a50 , (O)R b50 , C(O)NR c50 R d50 , C(O)OR a50 , OC(O)R b50 , OC(O)NR c50 R d50 , NR c50 R d50 , NR c50 C(O)R b50 , NR c50 C(O)OR a50 , NR c50 C(O)NR c50 R d50 , C(═NR e50 )R b50 , C(═NOR a50 )R b50 , C(═NR e50 )NR c50 R d50 , NR c50 C(═NR e50 )NR c50 R d50 , NR c50 S(O)R b50 , NR c50 S(O) 2 R b50 , NR c50 S(O) 2 NR c50 R d50 , S(O)R b50 , S(O)NR c50 R d50 , S(O) 2 R b50 , and S(O) 2 NR c50 R d50 ; 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 51 ;

each R 51 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, D, CN, OR a51 , SR a51 , C(O)R b51 , C(O)NR c51 R d51 , C(O)OR a51 , NR c51 R d51 , NR c51 C(O)R b51 , NR c51 C(O)OR a51 , NR c51 C(O)NR c51 R d51 , NR c51 S(O)R b51 , NR c51 S(O) 2 R b51 , NR c51 S(O) 2 NR c51 R d51 , S(O)R b51 , S(O)NR c51 R d51 , S(O) 2 R b51 , and S(O) 2 NR c51 R d51 , 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 52 ;

each R 52 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, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a52 , SR a52 , C(O)R b52 , C(O)NR c52 R d52 , C(O)OR a52 , NR c52 R d52 , NR c52 C(O)R b52 , NR c52 C(O)R a52 , NR c52 (O)NR c52 R d52 , NR c52 S(O)R b52 , NR c52 S(O) 2 R b52 , NR c52 S(O) 2 NR c52 R d52 , S(O)R b52 , S(O)NR c52 R d52 , S(O) 2 R b52 , and S(O) 2 NR c52 R d52 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 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 60 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, D, CN, NO 2 , OR a60 , SR a60 , C(O)R b60 , C(O)NR c60 R d60 , C(O)OR a60 , OC(O)R b60 , OC(O)NR c60 R d60 , NR c60 R d60 , NR c60 C(O)R b60 , NR c60 C(O)OR a60 , NR c60 C(O)NR c60 R d60 , C(═NR e60 )R b60 , C(═NR a60 )R b60 , C(═NR e60 )NR c60 R d60 , NR c60 C(═NR e60 )NR c60 R d60 , NR c60 S(O)R b60 , NR c60 S(O) 2 R b60 , NR c60 S(O) 2 NR c60 R d60 , S(O)R b60 , S(O)NR c60 R d60 , S(O) 2 R b60 , and S(O) 2 NR c60 R d60 , 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, C6-11) 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 61 ;

each R 61 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, D, CN, OR a61 , SR a61 , (O)R b61 , C(O)NR c61 R d61 , C(O)OR a61 , NR c61 R d61 , NR c61 C(O)R b61 , NR c61 C(O)O R a61 , NR c61 C(O)NR c61 R d61 , NR c61 S(O)R b61 , NR c61 S(O) 2 R b61 , NR c61 S(O) 2 NR c61 R d61 , S(O)R b61 , S(O)NR c61 R d61 , S(O) 2 R b61 , and S(O) 2 NR c61 R d61 , 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 62 ;

each R 62 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, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a62 , SR a62 , C(O)R b62 , C(O)NR c62 R d62 , C(O)OR a62 , NR c62 R d62 , NR c62 (O)R b62 , NR c62 C(O)OR a62 NR c62 C(O)NR c62 R d62 , NR c62 S(O)R b62 , NR c62 S(O) 2 R b62 , NR c62 S(O) 2 NR c62 R d62 , S(O)R b62 , S(O)NR c62 R d62 , S(O) 2 R b62 , and S(O) 2 NR c62 R d62 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 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 b1 , 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 10 ;

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 10 ;

each R c1 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 b2 , 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 20 ;

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 or 3 substituents independently selected from R 20 ;

each R e2 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 b3 , 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 3-10 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 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, 3, or 4 substituents independently selected from R 30 ;

each R e3 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 a4 , R b4 , 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 3-10 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 40 ;

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, 3, or 4 substituents independently selected from R 40 ;

each R e4 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 a5 , R b5 , R c5 and R d5 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 50 ;

or any R c5 and R d5 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 50 ;

each R e5 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 a6 , R b6 , R c6 and R d6 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 60 ;

or any R c6 and R d6 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 60 ;

each R e6 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 a10 , R b10 , R c10 and R d10 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 c10 and R d10 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 e10 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 a11 , R b11 , R c11 and R d11 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 c11 and R d11 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 a12 , R b12 , R c12 and R d12 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 a20 , R b20 , R c20 and R d20 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 c20 and R d20 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 e20 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 a21 , R b21 , R c21 and R d21 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 c21 and R d21 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 a22 , R b22 , R c22 and R d22 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 a30 , R b30 , R c30 and R d30 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 31 ;

or any R c30 and R d30 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 31 ;

each R e30 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 a31 , R b31 , R c31 and R d31 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 32 ;

or any R c31 and R d31 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 32 ;

each R a32 , R b32 , R c32 and R d32 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 a40 , R b40 , R c40 and R d40 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 41 ;

or any R c40 and R d40 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 41 ;

each R e40 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 a41 , R b41 , R c41 and R d41 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 42 ;

or any R c41 and R d41 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 42 ;

each R a42 , R b42 , R c42 and R d42 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 a50 , R b50 , R c50 and R d50 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 51 ;

or any R c50 and R d50 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 51 ;

each R e50 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 a51 , R b51 , R c51 and R d51 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 52 ;

or any R c51 and R d51 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 52 ;

each R a52 , R b52 , R c52 and R d52 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 a60 , R b60 , R c60 and R d60 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 61 ;

or any R c60 and R d60 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 61 ;

each R e60 is independently selected from H, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkylthio, C 1-6 alkyl sulfonyl, 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 a61 , R b61 , R c61 and R d61 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 62 ;

or any R c61 and R d61 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 62 ;

each R a62 , R b62 , R c62 and R d62 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 ; and

each R g is independently selected from D, 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 alkoxycarbonylamino, C 1-6 alkylcarbonyloxy, aminocarbonyloxy, C 1-6 alkyl aminocarbonyloxy, di(C 1-6 alkyl)aminocarbonyloxy, 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, aminocarbonyl amino, C 1-6 alkylaminocarbonylamino, and di(C 1-6 alkyl)aminocarbonylamino.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is CR 6 .

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 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, halo, D, CN, NO 2 , OR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , NR c1 R d1 , NR c1 C(O)R b1 , 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 10 .

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from H, C 1-6 alkyl, C 2-6 alkynyl, 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 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 10 .

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl; wherein said C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 10 .

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from pyrazol-4-yl, imidazol-4-yl, 6-oxo-1,6-dihydropyridin-3-yl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl, pyridin-3-yl, and pyrimidin-5-yl, each of which is optionally substituted with 1 or 2 substituents independently selected from R 10 .

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein, R 1 is pyrazolyl optionally substituted with 1 or 2 substituents independently selected from R 10 .

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein, R 1 is phenyl optionally substituted with 1 or 2 substituents independently selected from R 10 .

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from H, 1-(2-hydroxyethyl)-1H-pyrazol-4-yl, 1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl, 1-(1-amino-2-methyl-1-oxopropan-2-yl)-1H-pyrazol-4-yl, 4-(morpholine-4-carbonyl)phenyl, 1H-pyrazol-4-yl, 1-(1-cyanopropan-2-yl)-1H-pyrazol-4-yl, 1-(2-hydroxybutyl)-1H-pyrazol-4-yl, 1-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl, 1-((5-cyanopyridin-3-yl)methyl)-1H-pyrazol-4-yl, 1-((2-cyanopyridin-4-yl)methyl)-1H-pyrazol-4-yl, 1-(pyrimidin-4-ylmethyl)-1H-pyrazol-4-yl, 1-(1-(2-cyanopyridin-4-yl)ethyl)-1H-pyrazol-4-yl, 4-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)phenyl, 4-(1,1-dioxidothiomorpholino)phenyl, 1-(pyrimidin-2-ylmethyl)-1H-pyrazol-4-yl, 1-((6-cyanopyridin-2-yl)methyl)-1H-pyrazol-4-yl, 4-(4-acetylpiperazin-1-yl)phenyl, 4-(4-(2-hydroxyacetyl)piperazin-1-yl)phenyl, 4-((4-acetylpiperazin-1-yl)methyl)phenyl, 4-((4-(2-hydroxyacetyl)piperazin-1-yl)methyl)phenyl, 4-(4-methylpiperazin-1-yl)phenyl, 4-((1S,4S)-2-oxa-5-azabicyclo [2.2.1]heptane-5-carbonyl)phenyl, 1-(cyanomethyl)-1H-pyrazol-4-yl, 1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl, 1-benzyl-1H-pyrazol-4-yl, 1-(2-(methylsulfonyl)ethyl)-1H-pyrazol-4-yl, 1-(1-cyanoethyl)-1H-pyrazol-4-yl, 1-(2,2-difluoroethyl)-1H-pyrazol-4-yl, 1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl, 1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl, 1-(2-cyanopropan-2-yl)-1H-pyrazol-4-yl, 1-cyclopropyl-1H-pyrazol-4-yl, 1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl, 1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl, 1-(1-methoxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl, 9-(1-(2-hydroxypropyl)-1H-pyrazol-4-yl, 1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl, 1-methyl-1H-imidazol-4-yl, 6-oxo-1,6-dihydropyridin-3-yl, 5-isopropyl-1H-pyrazol-4-yl, 5,6-dihydro-4H-pyrrolo [1,2-b]pyrazol-3-yl, 5-(2-hydroxypropan-2-yl)pyridin-3-yl, 2-(methylamino)pyrimidin-5-yl, 1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl, 1-(2-morpholinoethyl)-1H-pyrazol-4-yl, 1-(2-(4-methylpiperazin-1-yl)ethyl)-1H-pyrazol-4-yl, 1-(3-hydroxypropyl)-1H-pyrazol-4-yl, 1-(2-cyanoethyl)-1H-pyrazol-4-yl, 1-(2-Amino-2-oxoethyl)-1H-pyrazol-4-yl, 6-(2-hydroxypropan-2-yl)pyridin-3-yl, 6-(2,2,2-trifluoroethyl)pyridin-3-yl, 6-(methylcarbamoyl)pyridin-3-yl, 4-hydroxycyclohex-1-en-1-yl, 5-hydroxypent-1-yn-1-yl, and 2-hydroxypropan-2-yl.

10. 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, D, CN, NO 2 , OR a10 , C(O)R b10 , C(O)NR c10 R d10 , C(O)OR a10 , OC(O)R b10 , NR c10 R d10 , NR c10 C(O)R b10 , S(O) 2 R b10 , and S(O) 2 NR c10 R d10 , 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 .

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, OR a10 , C(O)NR c10 R d10 , and NR c10 R d10 ; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 .

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, OR a10 , C(O)NR c10 R d10 , NR c10 R d10 , 1,1-dioxidotetrahydro-2H-thiopyranyl, 1,1-dioxidothiomorpholino, piperazinyl, tetrahydro-2H-pyranyl, piperidinyl, cyclopropyl, tetrahydrofuran-3-yl, and cyclohexenyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 .

13. 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, D, CN, OR a11 , C(O)NR c11 R d11 , C(O)OR a11 , NR c11 R d11 , S(O)NR c11 R d11 , S(O) 2 R b11 , and S(O) 2 NR c11 R d11 ; 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 .

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently selected from C 1-6 alkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, CN, OR a11 , C(O)R b11 , C(O)NR c11 R d11 , NR c11 R d11 , and S(O) 2 R b11 ; wherein said C 1-6 alkyl, 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 .

15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 12 is independently selected from C 1-6 alkyl, halo, CN, OR a12 , and C(O)R b12; wherein said C 1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R g .

16. 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, D, CN, NO 2 , OR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 .

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

18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, D, CN, NO 2 , OR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , NR c3 R d3 , S(O) 2 R b3, and S(O) 2 NR c3 R d3 .

19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is H.

20. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, halo, D, CN, NO 2 , OR a4 , C(O)R b4, C(O)NR c4 R d4 , C(O)OR a4 , NR c4 R d4 , S(O) 2 R b4 , and S(O) 2 NR c4 R d4 .

21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is H.

22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 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, halo, D, CN, NO 2 , OR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , 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 3-10 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 50 .

23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from H, C 1-6 alkyl, and C 6-10 aryl; wherein said C 1-6 alkyl and C 6-10 aryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 50 .

24. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from C 1-6 alkyl, and phenyl; wherein said C 1-6 alkyl and phenyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 50 .

25. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is phenyl optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 50 .

26. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 5 is H, methyl or 2,6-dichlorophenyl.

27. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 50 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, halo, D, CN, OR a50 , C(O)R b50 , C(O)NR c50 R d50 , C(O)OR a50 , NR c50 R d50 , NR c50 R b50 , S(O) 2 R b50 , and S(O) 2 NR c50 R d50 .

28. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 50 is independently selected from halo.

29. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 50 is Cl.

30. The compound of claim 1 , wherein the compound has Formula II:

or a pharmaceutically acceptable salt thereof.

31. The compound of claim 1 , wherein the compound has Formula IIIa or Formula IIIb:

or a pharmaceutically acceptable salt thereof.

32. The compound of claim 1 , wherein the compound has Formula IVa or Formula IVb:

or a pharmaceutically acceptable salt thereof.

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

R 1 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, halo, D, CN, NO 2 , OR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , NR c1 R d1 , NR c1 C(O)R b1 , 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 10 ;

R 2 is H;

R 3 is H;

R 4 is H;

R 5 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, halo, D, CN, NO 2 , OR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , 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 3-10 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 50 ;

Z is CR 6 ;

R 6 is H;

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, D, CN, NO 2 , OR a10 , C(O)R b10 , C(O)NR c10 R d10 , C(O)OR a10 , OC(O)R b10 , NR c10 R d10 , NR c10 C(O)R b10 , S(O) 2 R b10 , and S(O) 2 NR c10 R d10 ; 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 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, D, CN, OR a11 , C(O)R b11 , C(O)NR c11 R d11 , C(O)OR a11 , NR c11 R d11 , S(O)NR c11 R d11 , S(O) 2 R b11 , and S(O) 2 NR c11 R d11 ; 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, C 3-6 cycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a12 , C(O)R b12 , C(O)NR c12 R d12 , C(O)OR a12 , NR c12 R d12 , NR c12 C(O)R b12 , S(O)NR c12 R d12 , S(O) 2 R b12 , and S(O) 2 NR c12 R d12 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 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 50 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, D, CN, NO 2 , OR a50 , C(O)R b50 , C(O)NR c50 R d50 , C(O)OR a50 , OC(O)R b50 , NR c50 R d50 , NR c50 C(O)R b50 , S(O) 2 R b50 , and S(O) 2 NR c50 R d50 ; 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 51 ;

each R 51 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, D, CN, OR a51 , C(O)R b51 , C(O)NR c51 R d51 , C(O)OR a51 , NR c51 R d51 , NR c51 C(O)R b51 , S(O) 2 R b51 , and S(O) 2 NR c51 R d51 ; 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 52 ;

each R 52 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, 5-6 membered heteroaryl, 4-7 membered heterocycloalkyl, halo, D, CN, OR a52 , C(O)R b52 , C(O)NR c52 R d52 , C(O)OR a52 , NR c52 R d52 , NR c52 C(O)R b52 , S(O) 2 R b52 , and S(O) 2 NR c52 R d52 ; wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, C 6-10 aryl, 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 g is independently selected from D, OH, CN, halo, C 1-6 alkyl, and C 1-6 haloalkyl.

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

R 1 is selected from H, C 1-6 alkyl, C 2-6 alkynyl, 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 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 10 ;

R 2 is H;

R 3 is H;

R 4 is H;

R 5 is selected from H, C 1-6 alkyl, and C 6-10 aryl; wherein said C 1-6 alkyl and C 6-10 aryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 50 ;

Z is CR 6 ;

R 6 is H;

each R 10 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, OR a10 , C(O)NR c10 R d10 , and NR c10 R d10 ; wherein said C 1-6 alkyl, C 3-10 cycloalkyl, and 4-10 membered heterocycloalkyl 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, 4-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, CN, OR a11 , C(O)R b11 , C(O)NR c11 R d11 , NR c11 R d11 and S(O) 2 R b11 ; wherein said C 1-6 alkyl, 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, halo, CN, OR a12 , and C(O)R b12 ; wherein said C 1-6 alkyl is optionally substituted with 1 or 2 substituents independently selected from R g ;

each R 50 is independently selected from halo;

each R a10 , R c10 and R d10 is independently selected from H and C 1-6 alkyl; wherein said 6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

or any R c10 and R d10 attached to the same N atom, together with the N atom to which they are attached, form a 6- or 7-membered heterocycloalkyl group optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 11 ;

each R a11 , R b11 , R c11 and R d11 is independently selected from H and C 1-6 alkyl; wherein said C 1-6 alkyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 12 ;

each R a12 and R b12 is independently selected from H and C 1-6 alkyl; wherein said C 1-6 alkyl is optionally substituted with R g ; and

R g is OH.

35. The compound of claim 1 , wherein the compound is selected from:

2-(2,6-Dichlorophenyl)-9-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)imidazo [2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-(1-Amino-2-methyl-1-oxopropan-2-yl)-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(4-(morpholine-4-carbonyl)phenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-(1-Cyanopropan-2-yl)-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(2-hydroxybutyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-((4-fluorotetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-((5-Cyanopyridin-3-yl)methyl)-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-((2-Cyanopyridin-4-yl)methyl)-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(pyrimidin-4-ylmethyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-(1-(2-Cyanopyridin-4-yl)ethyl)-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(4-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)phenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(4-(1,1-dioxidothiomorpholino)phenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(pyrimidin-2-ylmethyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-((6-Cyanopyridin-2-yl)methyl)-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(4-(4-Acetylpiperazin-1-yl)phenyl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(4-(4-(2-hydroxyacetyl)piperazin-1-yl)phenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(4-((4-Acetylpiperazin-1-yl)methyl)phenyl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(4-((4-(2-hydroxyacetyl)piperazin-1-yl)methyl)phenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(4-(4-methylpiperazin-1-yl)phenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(4-((1S,4S)-2-Oxa-5-azabicyclo[2.2.1]heptane-5-carbonyl)phenyl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-(Cyanomethyl)-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-Benzyl-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(2-(methylsulfonyl)ethyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-(1-Cyanoethyl)-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(1-hydroxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-(2-Cyanopropan-2-yl)-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-Cyclopropyl-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(2-(dimethylamino)ethyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(1-methoxy-2-methylpropan-2-yl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(2-hydroxypropyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(3-(dimethylamino)propyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-methyl-1H-imidazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(6-oxo-1,6-dihydropyridin-3-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(5-isopropyl-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(5-(2-hydroxypropan-2-yl)pyridin-3-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(2-(methylamino)pyrimidin-5-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(tetrahydrofuran-3-yl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(2-morpholinoethyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(2-(4-methylpiperazin-1-yl)ethyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(1-(3-hydroxypropyl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-(2-Cyanoethyl)-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

9-(1-(2-Amino-2-oxoethyl)-1H-pyrazol-4-yl)-2-(2,6-dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(6-(2,2,2-trifluoroethyl)pyridin-3-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(6-(methylcarbamoyl)pyridin-3-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(4-hydroxycyclohex-1-en-1-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(5-hydroxypent-1-yn-1-yl)imidazo [2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)-9-(2-hydroxypropan-2-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-(2,6-Dichlorophenyl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide;

2-Methyl-9-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)imidazo[2,1-f][1,6]naphthyridine-3-carboxamide; and

9-(1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)imidazo [2,1-f][1,6]naphthyridine-3-carboxamide,

or a pharmaceutically acceptable salt of any of the aforementioned.

36. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

37. A method of inhibiting an FGFR3 enzyme comprising contacting said enzyme with a compound of claim 1 or a pharmaceutically acceptable salt thereof.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 10, 2023

From: LI, XIN; STYDUHAR, EVAN; SWYKA, ROBERT; VECHORKIN, OLEG; YAO, WENQING

To: INCYTE CORPORATION

Reel/Frame 063597/0206 →

Continuity (2)

Provisional Application 63208664 · Jun 9, 2021

Related Publication 20230002385A1 · Jan 5, 2023

Cited By (2)

US 12,428,420 US 12,552,804