Granted Patent B2

US 12,600,717 · App. 17/812,310 · Granted Apr 14, 2026

Inventors: Zhenwu Li (Wilmington, DE); Zhiyong Yu (Hockessin, DE); Jeremy Roach (Philadelphia, PA); Gia Hoang (Wilmington, DE); Bin Hu (Garnet Valley, PA); Gencheng Li (Claymont, DE); Rory McAtee (Kennett Square, PA); Ken Mukai (Wilmington, DE); Rocco Policarpo (Wilmington, DE); Robert Susick (Wilmington, DE); Xiaozhao Wang (Mt. Laurel, NJ); Wenqing Yao (Wilmington, DE)

Assignee: Incyte Corporation

C07D471/04A61P35/00A61P35/02A61P35/04C07D519/00

Abstract

Claims (221)

1 . A compound having Formula (1):

or a pharmaceutically acceptable salt thereof, wherein:

X Y is selected from —NR 5 —C(═O)—, —N═N—, and —N═CR 6 —;

R 1 is selected from H, D, C 1-2 alkyl, and C 1-2 haloalkyl; wherein said C 1-2 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 11 ;

Cy 1 is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 6-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 6-10 membered heteroaryl each 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 a ring-forming carbon atom of 6-10 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 6-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 10 ;

R 4 is selected from H, C 1-3 alkyl, C 1-3 haloalkyl, 5-10 membered heteroaryl, OR a3 , and NR c3 R j3 ; wherein said C 1-3 alkyl and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 30 ; or

R 4 is selected from

R 5 is selected from H, C 1-2 alkyl, and C 1-2 haloalkyl;

R 7 is selected from H, C 1-3 alkyl, C 1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, F, Cl, D, CN, OR a7 , and NR c7 R d7 ; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 70 ;

Cy 2 is selected from

when Cy 2 is Cy 2 -a and X Y is —N═CR 6 —, then, R 6 is selected from H, D, C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl; wherein said C 1-3 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 60 ;

when Cy 2 is Cy 2 -a, then R 2 is selected from H, C 1-2 alkyl, C 1-2 haloalkyl, F, Cl, and —CH 2 CH 2 CN;

when Cy 2 is Cy 2 -b and X Y is —N═CR 6 —, then R 6 is selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl; wherein said C 1-3 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 60 ;

when Cy 2 is Cy 2 -b, then R 2 is selected from H, C 1-2 alkyl, C 1-2 haloalkyl, F, —CH 2 CH 2 CN,

each R 10 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, halo, D, CN, OR a10 , C(O)NR c10 R d10 , NR c10 C(O)OR a10 , NR c10 C(O)NR c10 R d10 , and NR c10 R d10 ; wherein said C 1-3 alkyl and C 3-6 cycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R g ;

each R 11 is independently selected from C 1-2 alkyl, C 1-2 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, halo, D, CN, OR a11 , and NR c11 R d11 ; wherein said C 12 alkyl, C 3-6 cycloalkyl, and 4-6 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R g ;

each R 21 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, halo, D, CN, OR a21 and NR c21 R d21 ;

each R 30 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a30 , C(O)NR c30 R d30 , NR c30 C(O)OR a30 , NR c30 C(O)NR c30 R d30 , and NR c30 R d30 ; wherein said C 1-3 alkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 31 each R 31 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, halo, D, and CN;

each R 60 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, OR a60 , C(O)R b60 , C(O)NR c60 R d60 , and NR c60 R d60 ; wherein said C 1-3 alkyl, 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 61 ;

each R 61 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, OR a61 , C(O)R b61 , and NR c61 R d61 ;

each R 70 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, OR a70 , and NR c70 R d70 ;

each R a3 and R c3 is independently selected from H, C 1-3 alkyl, C 1-3 haloalkyl, 5-6 membered heteroaryl, and phenyl; wherein said C 1-3 alkyl, 5-6 membered heteroaryl, and phenyl are each optionally substituted with 1 or 2 substituents independently selected from R 30 ;

each R j3 is independently selected from C 1-3 alkyl and C 1-3 haloalkyl;

each R a7 , R c7 and R d7 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

wherein said C 1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 70 ;

each R a10 , R c10 and R d10 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

each R a11 , R c11 and R d11 , is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

R b20 is selected from NH 2 , C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; wherein said C 1-3 alkyl, 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 21 ;

each R a21 , R c21 and R d21 , is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

each R a30 , R c30 and R d30 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

each R a60 , R b60 , R c60 and R d60 is independently selected from H, C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl; wherein said C 1-3 alkyl, 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 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-, 7-, 8-, or 9-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from R 61 ;

each R a61 , R b61 R c61 and R d61 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

each R a70 , R c70 and R d70 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl; and

each R g is independently selected from D, OH, CN, halo, C 1-2 alkyl, amino, and C 1-2 haloalkyl;

provided that the compound of Formula I is other than

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-4-(3-(dimethylamino)azetidin-1-

yl)-6-fluoro-7-(7-fluoronaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-

dimethylpropanamide,

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-2-ethyl-6-

fluoro-7-(7-fluoro-3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile,

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-

hydroxynaphthalen-1-yl)-2-((3-oxomorpholino)methyl)-1H-imidazo[4,5-c]quinolin-8-

yl)propanenitrile,

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-4-(3-(dimethylamino)azetidin-1-

yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-2-yl)-N-methyl-N-(pyridin-

2-ylmethyl)propanamide, and

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-

hydroxynaphthalen-1-yl)-2-(2-(piperazin-1-yl)thiazol-4-yl)-1H-imidazo[4,5-c]quinolin-8-

yl)propanenitrile.

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

X Y is selected from —NR 5 —C(═O)—, —N═N—, and —N═CR 6 —;

R 1 is selected from H, D, C 1-2 alkyl, and C 1-2 haloalkyl; wherein said C 1-2 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 11 ;

Cy 1 is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 6-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 6-10 membered heteroaryl each 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 a ring-forming carbon atom of 6-10 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 6-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 10 ;

R 4 is selected from OR a3 ;

R 5 is selected from H, C 1-2 alkyl, and C 1-2 haloalkyl;

R 7 is selected from H, C 1-3 alkyl, C 1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, F, Cl, D, CN, OR a7 , and NR c7 R d7 ; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 70 ;

Cy 2 is selected from

when Cy 2 is Cy 2 -a and X Y is —N═CR 6 —, then, R 6 is selected from H, D, C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl; wherein said C 1-3 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 60 ;

when Cy 2 is Cy 2 -a, then R 2 is selected from H, C 1-2 alkyl, C 1-2 haloalkyl, F, Cl, and —CH 2 CH 2 CN;

when Cy 2 is Cy 2 -b and X Y is —N═CR 6 —, then R 6 is selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl; wherein said C 1-3 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 60 ;

when Cy 2 is Cy 2 -b then R 2 is selected from H, C 1-2 alkyl C 1-2 haloalkyl, F, —CH 2 CH 2 CN,

each R 10 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, halo, D, CN, OR a10 , C(O)NR c10 R d10 , NR c10 C(O)OR a10 , NR c10 C(O)NR c10 R d10 , and NR c10 R d10 ; wherein said C 1-3 alkyl and C 3-6 cycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 9 ;

each R 11 is independently selected from C 1-2 alkyl, C 1-2 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, halo, D, CN, OR a11 , and NR c11 R d11 ; wherein said C 1-2 alkyl, C 3-6 cycloalkyl, and 4-6 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 9 ;

each R 21 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, halo, D, CN, OR a21 and NR c21 R d21 ;

each R 30 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a30 , C(O)NR c30 R d30 , NR c30 C(O)OR a30 , NR c30 C(O)NR c3O R d30 and NR c30 R d30 ; wherein said 1-3 alkyl and 4-6 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 31 ;

each R 31 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, halo, D, and CN;

each R 60 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, OR a60 , C(O)R b60 , C(O)NR c60 R d60 , and NR c60 R d60 ; wherein said C 1-3 alkyl, 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 61 ;

each R 61 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, OR a61 , C(O)R b61 , and NR c61 R d61 ;

each R 70 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, OR a70 , and NR c70 R d70 ;

each R a3 is independently selected from H, C 1-3 alkyl, C 1-3 haloalkyl, 5-6 membered heteroaryl, and phenyl; wherein said C 1-3 alkyl, 5-6 membered heteroaryl, and phenyl are each optionally substituted with 1 or 2 substituents independently selected from R 30 ;

each R a7 , R c7 and R d7 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

wherein said C 1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 70 ;

each R a10 , R c10 and R d10 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

each R a11 , R c11 and R d11 , is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

R b20 is selected from NH 2 , C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; wherein said C 1-3 alkyl, 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 21 ;

each R a21 , R c21 and R d21 , is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

each R a30 , R c30 and R d30 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

each R a60 , R b60 , R c60 and R d60 is independently selected from H, C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl; wherein said C 1-3 alkyl, 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 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-, 7-, 8-, or 9-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from R 61 ;

each R a61 , R b61 R c61 and R d61 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

each R a70 R c70 and R d70 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl; and

each R g is independently selected from D, OH, CN, halo, C 1-2 alkyl, amino, and C 1-2 haloalkyl.

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

X Y is selected from —NR 5 —C(═O)—, —N═N—, and —N═CR 6 —;

R 1 is selected from H, D, C 1-2 alkyl, and C 1-2 haloalkyl; wherein said C 1-2 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 11 ;

Cy 1 is selected from C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C 6-10 aryl and 6-10 membered heteroaryl; wherein the 4-10 membered heterocycloalkyl and 6-10 membered heteroaryl each 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 a ring-forming carbon atom of 6-10 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 6-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 10 ;

R 4 is selected from OR a3 ;

R 5 is selected from H, C 1-2 alkyl, and C 1-2 haloalkyl;

R 7 is selected from H, C 1-3 alkyl, C 1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, F, Cl, D, CN, OR a7 , and NR c7 R d7 ; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 70 ;

Cy 2 is selected from

when Cy 2 is Cy 2 -a and X Y is —N═CR 6 —, then, R 6 is selected from H, D, C 1-3 alkyl, and C 1-3 haloalkyl; wherein said C 1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 60 ;

when Cy 2 is Cy 2 -a, then R 2 is selected from H, C 1-2 alkyl, C 1-2 haloalkyl, F, Cl, and —CH 2 CH 2 CN;

when Cy 2 is Cy 2 -b and X Y is —N═CR 6 —, then R 6 is selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl; wherein said C 1-3 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl, are each optionally substituted with 1 or 2 substituents independently selected from R 60 ;

when Cy 2 is Cy 2 -b, then R 2 is selected from H, C 1-2 alkyl, C 1-2 haloalkyl, F, —CH 2 CH 2 CN,

each R 10 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, halo, D, CN, OR a10 , C(O)NR c10 R d10 , and NR c10 R d10 ; wherein said C 1-3 alkyl and C 3-6 cycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 9 ;

each R 11 is independently selected from C 1-2 alkyl, C 1-2 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, halo, D, CN, OR a11 , and NR c11 R d11 ; wherein said C 12 alkyl, C 3-6 cycloalkyl, and 4-6 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R g ;

each R 21 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, halo, D, and CN;

each R 30 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, OR a30 , C(O)NR c30 R d30 , and NR c30 R d30 ; wherein said C 1-3 alkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 31 ;

each R 31 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, halo, D, and CN;

each R 60 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, OR a60 , C(O)R b60 , C(O)NR 60 R d60 , and NR c60 R d60 ; wherein said C 1-3 alkyl, 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 61 ;

each R 61 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, OR a61 , C(O)R b61 , and NR c61 R d61 ;

each R 70 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, and CN;

each R a3 is independently selected from H, C 1-3 alkyl, C 1-3 haloalkyl, 5-6 membered heteroaryl, and phenyl; wherein said C 1-3 alkyl, 5-6 membered heteroaryl, and phenyl are each optionally substituted with 1 or 2 substituents independently selected from R 30 ;

each R a7 , R c7 and R d7 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl; wherein said C 1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 70 ;

each R a10 , R c10 and R d10 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

each R a11 , R c11 and R d11 , is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

R b20 is selected from NH 2 , C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; wherein said C 1-3 alkyl, 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 21 ;

each R a21 , R c21 and R d21 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

each R a30 , R c30 and R d30 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl;

each R a60 , R b60 , R c60 and R d60 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl; wherein said C 1-3 alkyl is optionally substituted with 1 or 2 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 9-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from R 61 ;

each R a61 , R b61 R c61 and R d61 is independently selected from H, C 1-3 alkyl, and C 1-3 haloalkyl; and

each R g is independently selected from D, OH, CN, halo, C 1-2 alkyl, amino, and C 1-2 haloalkyl.

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

X Y is selected from —NR 5 —C(═O)—, —N═N—, and —N═CR 6 —;

R 1 is selected from H, and C 1-2 alkyl; wherein said C 1-2 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 11 ;

Cy 1 is selected from C 3-10 cycloalkyl, C 6-10 aryl and 6-10 membered heteroaryl; wherein the 6-10 membered heteroaryl each 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 6-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the C 3-10 cycloalkyl, C 6-10 aryl and 6-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 10 ;

R 4 is selected from OR a3 ;

R 5 is H;

R 7 is selected from phenyl, 5-6 membered heteroaryl, F, and OR a7 ; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 70 ;

Cy 2 is selected from

when Cy 2 is Cy 2 -a and X Y is —N═CR 6 —, then, R 6 is H;

when Cy 2 is Cy 2 -a, then R 2 is Cl;

when Cy 2 is Cy 2 -b and X Y is —N═CR 6 —, then R 6 is selected from C 1-3 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-10 membered heteroaryl; wherein said C 1-3 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 60 ;

when Cy 2 is Cy 2 -b, then R 2 is selected from H, C 1-2 alkyl, —CH 2 CH 2 CN,

each R 10 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, halo, CN, OR a10 , and NR c10 R d10 ; wherein said C 1-3 alkyl and C 3-6 cycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R 9 ;

each R 11 is independently selected from 4-6 membered heterocycloalkyl, and OR a11 ;

wherein said 4-6 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from R g ;

each R 21 is CN;

each R 30 is independently selected from 4-10 membered heterocycloalkyl and C(O)NR c30 R d30 ; wherein said 4-10 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from R 31 ;

each R 31 is independently selected from C 1-3 alkyl;

each R 60 is independently selected from C 1-3 alkyl, C 3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, C(O)R b60 , C(O)NR c60 R d60 , and NR c60 R d60 ; wherein said C 1-3 alkyl, 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 61 ;

each R 61 is independently selected from phenyl, 5-6 membered heteroaryl, and C(O)R b61 ;

each R 70 is independently selected from phenyl, 5-6 membered heteroaryl, and CN;

each R a3 is independently selected from C 1-3 alkyl, and phenyl; wherein said C 1-3 alkyl and phenyl are each optionally substituted with 1 or 2 substituents independently selected from R 30 ;

each R a7 is C 1-3 alkyl; wherein said C 1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 70 ;

each R a10 , R c10 and R d10 is H;

each R a11 is H;

R b20 is selected from NH 2 , C 1-3 alkyl, C 3-6 cycloalkyl, and 5-6 membered heteroaryl; wherein said C 1-3 alkyl, C 3-6 cycloalkyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 21 ;

each R c30 and R d30 is independently selected from H and C 1-3 alkyl;

each R b60 , R c60 and R d60 is independently selected from H and C 1-3 alkyl; wherein said C 1-3 alkyl is optionally substituted with 1 or 2 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 6- or 9-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from R 61 ;

each R b61 is C 1-3 alkyl; and

each R g is CN.

5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X Y is —NR 5 —C(═O)— or —N═N—.

6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X Y is —N═CR 6 —.

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

8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is selected from C 6-10 aryl and 6-10 membered heteroaryl; wherein the 6-10 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 a ring-forming carbon atom of 6-10 membered heteroaryl is optionally substituted by oxo to form a carbonyl group; and wherein the C 6-10 aryl and 6-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R 10 .

9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Cy 1 is selected from

10 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from

11 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from H, C 1-3 alkyl, C 1-3 haloalkyl, 5-10 membered heteroaryl, OR a3 , and NR c3 R j3 ; wherein said C 1-3 alkyl and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 30 .

12 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 7 is selected from phenyl, 5-6 membered heteroaryl, F and OR a7 ; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R 70 .

13 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein when Cy 2 is Cy 2 -a and X Y is —N═CR 6 —, then, R 6 is H.

14 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein when Cy 2 is Cy 2 -a, then R 2 is Cl.

15 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein when Cy 2 is Cy 2 -b and X Y is —N═CR 6 —, then R 6 is selected from C 1-3 alkyl, and C 1-3 haloalkyl; wherein said C 1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 60 .

16 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein when Cy 2 is Cy 2 -b, then R 2 is selected from H, C 1-2 alkyl, —CH 2 CH 2 CN,

17 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 10 is independently selected from C 1-3 alkyl, C 1-3 haloalkyl, C 3-6 cycloalkyl, halo, CN, OR a10 , and NR c10 R d10 ; wherein said C 1-3 alkyl and C 3-6 cycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R g .

18 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently selected from 4-6 membered heterocycloalkyl and OR a11 , wherein said 4-6 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from R g .

19 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 21 is independently selected from halo, CN, and OR a21 .

20 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 30 is independently selected from 4-10 membered heterocycloalkyl and C(O)NR c30 R d30 ; wherein said 4-10 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from R 31 .

21 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 31 is independently selected from C 1-3 alkyl and C 1-3 haloalkyl.

22 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 60 is independently selected from C 1-3 alkyl, C(O)NR c60 R d60 , and NR c60 R d60 ; wherein said C 1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 61 .

23 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 61 is independently selected from phenyl, 5-6 membered heteroaryl, and C(O)R b61 .

24 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 70 is independently selected from phenyl, 5-6 membered heteroaryl, and CN.

25 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R g is independently selected from OH, CN, and halo.

26 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R a3 is independently selected from C 1-3 alkyl; wherein said C 1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 30 .

27 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R b20 is selected from NH 2 and C 1-3 alkyl; wherein said C 1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R 21 .

28 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R b60 , R c60 and R d60 is independently selected from H and C 1-3 alkyl; wherein said C 1-3 alkyl is optionally substituted with 1 or 2 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 6- or 9-membered heterocycloalkyl group optionally substituted with 1 or 2 substituents independently selected from R 61 .

29 . The compound of claim 1 , wherein the compound of Formula I is selected from:

1-(3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-8-methyl-1H-imidazo[4,5-c]quinolin-2-yl)piperidin-1-yl)ethan-1-one;

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-8-methyl-1H-imidazo[4,5-c]quinolin-2-yl)-1-(4-(pyrimidin-2-yl)piperazin-1-yl)propan-1-one;

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-2-(3-oxo-3-(7-oxa-2-azaspiro[3.5]nonan-2-yl)propyl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(2-(3-(4-acetylpiperazin-1-yl)-3-oxopropyl)-1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-2-((2-oxopyrrolidin-1-yl)methyl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

4-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-2-ethyl-6-fluoro-8-(oxazol-5-yl)-1H-imidazo[4,5-c]quinolin-7-yl)naphthalen-2-ol;

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-2-ethyl-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-8-yl)-3-(1H-pyrazol-1-yl)propanenitrile;

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-2-ethyl-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-8-yl)-3-(4-(hydroxymethyl)-1H-pyrazol-1-yl)propanenitrile;

3-(8-((1H-pyrazol-1-yl)methyl)-1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-dimethylpropanamide;

3-(1-(2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-7-(2,3-dichloro-6-hydroxyphenyl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-dimethylpropanamide;

3-(1-(2-azabicyclo[2.1.1]hexan-5-yl)-7-(3-chloro-2-cyclopropyl-5-hydroxyphenyl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-dimethylpropanamide;

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-6-(3-cyanophenyl)-4-(3-(dimethylamino)azetidin-1-yl)-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-dimethylpropanamide;

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-4-(3-(dimethylamino)azetidin-1-yl)-7-(3-hydroxynaphthalen-1-yl)-6-(1-(pyridin-2-yl)-1H-pyrazol-4-yl)-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-dimethylpropanamide;

3-(6-(benzyloxy)-1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-4-(3-(dimethylamino)azetidin-1-yl)-7-(7-fluoronaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-dimethylpropanamide;

3-(1-((endo)2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-9-(hydroxymethyl)-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-dimethylpropanamide;

3-(1-((endo)2-azabicyclo[2.1.1]hexan-5-yl)-9-((3-cyanopyrrolidin-1-yl)methyl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-dimethylpropanamide;

3-(1-((endo)-2-Azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-2-ethyl-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-4-yl)-4-fluoro-N-methylbenzamide;

3-(1-((endo)-2-Azabicyclo[2.1.1]hexan-5-yl)-2-ethyl-4-(1-ethyl-6-oxo-1,6-dihydropyridin-3-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

5-(1-((endo)-2-Azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-2-ethyl-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-4-yl)-N-methylpicolinamide;

3-(1-((endo)-2-Azabicyclo[2.1.1]hexan-5-yl)-2-ethyl-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-(oxazol-2-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(4-([1,2,4]Triazolo[1,5-a]pyridin-7-yl)-1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-2-ethyl-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(1-((endo)-2-Azabicyclo[2.1.1]hexan-5-yl)-2-ethyl-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(1-((endo)-2-Azabicyclo[2.1.1]hexan-5-yl)-2-ethyl-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-methyl-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(1-((endo)-2-Azabicyclo[2.1.1]hexan-5-yl)-2-ethyl-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-phenoxy-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(1-((endo)-2-Azabicyclo[2.1.1]hexan-5-yl)-2-cyclopropyl-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(1-((endo)-2-Azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-2-(1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(1-((endo)-2-Azabicyclo[2.1.1]hexan-5-yl)-2-(1-cyclobutyl-1H-1,2,3-triazol-4-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-4-(((S)-1-methylpyrrolidin-2-yl)methoxy)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(1-(2-azabicyclo[2.1.1]hexan-5-yl)-2-ethyl-6-fluoro-4-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-7-(5-methyl-1H-indol-3-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

4-((1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-2-(2-(methylamino)ethyl)-1H-imidazo[4,5-c]quinolin-8-yl)methyl)benzonitrile;

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-2-ethyl-6-fluoro-7-(5-fluoro-1H-indol-3-yl)-4-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(7-(3-aminoisoquinolin-1-yl)-1-endo-(2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-dimethylpropanamide;

3-(7-(6-amino-3-(trifluoromethyl)pyridin-2-yl)-1-endo-(2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-dimethylpropanamide;

3-(1-endo-(2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-7-(7,7-difluoro-5,6,7,8-tetrahydronaphthalen-1-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-1H-imidazo[4,5-c]quinolin-2-yl)-N,N-dimethylpropanamide;

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-2-(1-phenyl-1H-pyrazol-3-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-2-(1-ethyl-1H-pyrazol-3-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(2-(1-benzyl-1H-pyrazol-3-yl)-1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-2-(2-(pyrimidin-2-yl)ethyl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

(3-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-4-(3-(dimethylamino)azetidin-1-yl)-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-2-(1H-indazol-5-yl)-1H-imidazo[4,5-c]quinolin-8-yl)propanenitrile;

8-(1-((2S,4S)-1-acetyl-2-(cyanomethyl)piperidin-4-yl)-8-chloro-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-imidazo[4,5-c]quinolin-7-yl)-1-naphthonitrile;

8-(8-chloro-1-((2S,4S)-1-(2-cyanoacetyl)-2-(cyanomethyl)piperidin-4-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-imidazo[4,5-c]quinolin-7-yl)-1-naphthonitrile;

8-(8-chloro-1-((2S,4S)-2-(cyanomethyl)-1-(1H-1,2,4-triazole-3-carbonyl)piperidin-4-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-imidazo[4,5-c]quinolin-7-yl)-1-naphthonitrile;

(2S,4S)-4-(8-chloro-7-(8-cyanonaphthalen-1-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-imidazo[4,5-c]quinolin-1-yl)-2-(cyanomethyl)piperidine-1-carboxamide;

8-(8-chloro-1-((2S,4S)-2-(cyanomethyl)-1-(cyclopropanecarbonyl)piperidin-4-yl)-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-imidazo[4,5-c]quinolin-7-yl)-1-naphthonitrile;

8-(1-((2S,4S)-1-acetyl-2-(cyanomethyl)piperidin-4-yl)-8-chloro-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-1H-[1,2,3]triazolo[4,5-c]quinolin-7-yl)-1-naphthonitrile; and

8-(1-((2S,4S)-1-acetyl-2-(cyanomethyl)piperidin-4-yl)-8-chloro-6-fluoro-4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-7-yl)-1-naphthonitrile;

or a pharmaceutically acceptable salt thereof.

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

31 . A method of inhibiting KRAS activity, said method comprising contacting a compound of claim 1 with KRAS.

32 . A method of treating a KRAS-mediated disease or disorder associated with abnormal expression or activity of KRAS interaction, said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , wherein the KRAS-mediated disease or disorder is selected from pancreatic cancer, colorectal cancer and lung cancer.

33 . A method of treating a KRAS-mediated disease or disorder wherein the KRAS protein harbors a G12D mutation, said method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1 , wherein the KRAS-mediated disease or disorder is selected from pancreatic cancer, colorectal cancer and lung cancer.

34 . The compound of claim 1 , wherein the compound of Formula I is 5-(1-((endo)-2-azabicyclo[2.1.1]hexan-5-yl)-8-(2-cyanoethyl)-2-ethyl-6-fluoro-7-(3-hydroxynaphthalen-1-yl)-1H-imidazo[4,5-c]quinolin-4-yl)-N-methylpicolinamide, or a pharmaceutically acceptable salt thereof.

Assignments (1)

Continuity (2)

References Cited (79)