# US 12,600,717 B2 · Tricyclic compounds as inhibitors of KRAS

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- Number: US 12,600,717 B2
- Document ID: US12600717B2
- Status: Granted
- Kind: B2
- Application number: 17/812,310
- Filed: 2022-07-13
- Published: 2023-04-13
- Granted: 2026-04-14
- Earliest claimed: 2021-07-14
- Assignees: Incyte Corporation
- Applicants: Incyte Corporation
- Inventors: Zhenwu Li; Zhiyong Yu; Jeremy Roach; Gia Hoang; Bin Hu; Gencheng Li; Rory McAtee; Ken Mukai; Rocco Policarpo; Robert Susick; Xiaozhao Wang; Wenqing Yao
- Web page: https://patentgrep.com/patent/US12600717B2

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed are compounds of Formula I (shown below), methods of using the compounds for inhibiting KRAS activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with KRAS activity such as cancer.

## Claims

### Claim 1

A compound having Formula (1):
or a pharmaceutically acceptable salt thereof, wherein:
XY is selected from —NR5—C(═O)—, —N═N—, and —N═CR6—;
R1 is selected from H, D, C1-2 alkyl, and C1-2 haloalkyl; wherein said C1-2 alkyl is optionally substituted with 1 or 2 substituents independently selected from R11;
Cy1 is selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 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 C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 6-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R10;
R4 is selected from H, C1-3 alkyl, C1-3 haloalkyl, 5-10 membered heteroaryl, ORa3, and NRc3Rj3; wherein said C1-3 alkyl and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R30; or
R4 is selected from
R5 is selected from H, C1-2 alkyl, and C1-2 haloalkyl;
R7 is selected from H, C1-3 alkyl, C1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, F, Cl, D, CN, ORa7, and NRc7Rd7; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R70;
Cy2 is selected from
when Cy2 is Cy2-a and XY is —N═CR6—, then, R6 is selected from H, D, C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R60;
when Cy2 is Cy2-a, then R2 is selected from H, C1-2 alkyl, C1-2 haloalkyl, F, Cl, and —CH2CH2CN;
when Cy2 is Cy2-b and XY is —N═CR6—, then R6 is selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R60;
when Cy2 is Cy2-b, then R2 is selected from H, C1-2 alkyl, C1-2 haloalkyl, F, —CH2CH2CN,
each R10 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, halo, D, CN, ORa10, C(O)NRc10Rd10, NRc10C(O)ORa10, NRc10C(O)NRc10Rd10, and NRc10Rd10; wherein said C1-3 alkyl and C3-6 cycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from Rg;
each R11 is independently selected from C1-2 alkyl, C1-2 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, halo, D, CN, ORa11, and NRc11Rd11; wherein said C12 alkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from Rg;
each R21 is independently selected from C1-3 alkyl, C1-3 haloalkyl, halo, D, CN, ORa21 and NRc21Rd21;
each R30 is independently selected from C1-3 alkyl, C1-3 haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, ORa30, C(O)NRc30Rd30, NRc30C(O)ORa30, NRc30C(O)NRc30Rd30, and NRc30Rd30; wherein said C1-3 alkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R31 each R31 is independently selected from C1-3 alkyl, C1-3 haloalkyl, halo, D, and CN;
each R60 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, ORa60, C(O)Rb60, C(O)NRc60Rd60, and NRc60Rd60; wherein said C1-3 alkyl, C3-6cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R61;
each R61 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, ORa61, C(O)Rb61, and NRc61Rd61;
each R70 is independently selected from C1-3 alkyl, C1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, ORa70, and NRc70Rd70;
each Ra3 and Rc3 is independently selected from H, C1-3 alkyl, C1-3 haloalkyl, 5-6 membered heteroaryl, and phenyl; wherein said C1-3 alkyl, 5-6 membered heteroaryl, and phenyl are each optionally substituted with 1 or 2 substituents independently selected from R30;
each Rj3 is independently selected from C1-3 alkyl and C1-3 haloalkyl;
each Ra7, Rc7 and Rd7 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R70;
each Ra10, Rc10 and Rd10 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
each Ra11, Rc11 and Rd11, is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
Rb20 is selected from NH2, C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each Ra21, Rc21 and Rd21, is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
each Ra30, Rc30 and Rd30 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
each Ra60, Rb60, Rc60 and Rd60 is independently selected from H, C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R61;
or any Rc60 and Rd60 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 R61;
each Ra61, Rb61 Rc61 and Rd61 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
each Ra70, Rc70 and Rd70 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl; and
each Rg is independently selected from D, OH, CN, halo, C1-2 alkyl, amino, and C1-2 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.

### Claim 2 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
XY is selected from —NR5—C(═O)—, —N═N—, and —N═CR6—;
R1 is selected from H, D, C1-2 alkyl, and C1-2 haloalkyl; wherein said C1-2 alkyl is optionally substituted with 1 or 2 substituents independently selected from R11;
Cy1 is selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 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 C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 6-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R10;
R4 is selected from ORa3;
R5 is selected from H, C1-2 alkyl, and C1-2 haloalkyl;
R7 is selected from H, C1-3 alkyl, C1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, F, Cl, D, CN, ORa7, and NRc7Rd7; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R70;
Cy2 is selected from
when Cy2 is Cy2-a and XY is —N═CR6—, then, R6 is selected from H, D, C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R60;
when Cy2 is Cy2-a, then R2 is selected from H, C1-2 alkyl, C1-2 haloalkyl, F, Cl, and —CH2CH2CN;
when Cy2 is Cy2-b and XY is —N═CR6—, then R6 is selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R60;
when Cy2 is Cy2-b then R2 is selected from H, C1-2 alkyl C1-2 haloalkyl, F, —CH2CH2CN,
each R10 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, halo, D, CN, ORa10, C(O)NRc10Rd10, NRc10C(O)ORa10, NRc10C(O)NRc10Rd10, and NRc10Rd10; wherein said C1-3 alkyl and C3-6 cycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R9;
each R11 is independently selected from C1-2 alkyl, C1-2 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, halo, D, CN, ORa11, and NRc11Rd11; wherein said C1-2 alkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R9;
each R21 is independently selected from C1-3 alkyl, C1-3 haloalkyl, halo, D, CN, ORa21 and NRc21Rd21;
each R30 is independently selected from C1-3 alkyl, C1-3 haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, ORa30, C(O)NRc30Rd30, NRc30C(O)ORa30, NRc30C(O)NRc3ORd30 and NRc30Rd30; wherein said 1-3 alkyl and 4-6 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R31;
each R31 is independently selected from C1-3 alkyl, C1-3 haloalkyl, halo, D, and CN;
each R60 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, ORa60, C(O)Rb60, C(O)NRc60Rd60, and NRc60Rd60; wherein said C1-3 alkyl, C3-6cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R61;
each R61 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, ORa61, C(O)Rb61, and NRc61Rd61;
each R70 is independently selected from C1-3 alkyl, C1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, ORa70, and NRc70Rd70;
each Ra3 is independently selected from H, C1-3 alkyl, C1-3 haloalkyl, 5-6 membered heteroaryl, and phenyl; wherein said C1-3 alkyl, 5-6 membered heteroaryl, and phenyl are each optionally substituted with 1 or 2 substituents independently selected from R30;
each Ra7, Rc7 and Rd7 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R70;
each Ra10, Rc10 and Rd10 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
each Ra11, Rc11 and Rd11, is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
Rb20 is selected from NH2, C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each Ra21, Rc21 and Rd21, is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
each Ra30, Rc30 and Rd30 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
each Ra60, Rb60, Rc60 and Rd60 is independently selected from H, C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R61;
or any Rc60 and Rd60 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 R61;
each Ra61, Rb61 Rc61 and Rd61 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
each Ra70Rc70 and Rd70 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl; and
each Rg is independently selected from D, OH, CN, halo, C1-2 alkyl, amino, and C1-2 haloalkyl.

### Claim 3 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
XY is selected from —NR5—C(═O)—, —N═N—, and —N═CR6—;
R1 is selected from H, D, C1-2 alkyl, and C1-2 haloalkyl; wherein said C1-2 alkyl is optionally substituted with 1 or 2 substituents independently selected from R11;
Cy1 is selected from C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 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 C3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C6-10 aryl and 6-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R10;
R4 is selected from ORa3;
R5 is selected from H, C1-2 alkyl, and C1-2 haloalkyl;
R7 is selected from H, C1-3 alkyl, C1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, F, Cl, D, CN, ORa7, and NRc7Rd7; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R70;
Cy2 is selected from
when Cy2 is Cy2-a and XY is —N═CR6—, then, R6 is selected from H, D, C1-3 alkyl, and C1-3 haloalkyl; wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R60;
when Cy2 is Cy2-a, then R2 is selected from H, C1-2 alkyl, C1-2 haloalkyl, F, Cl, and —CH2CH2CN;
when Cy2 is Cy2-b and XY is —N═CR6—, then R6 is selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-10 membered heteroaryl, are each optionally substituted with 1 or 2 substituents independently selected from R60;
when Cy2 is Cy2-b, then R2 is selected from H, C1-2 alkyl, C1-2 haloalkyl, F, —CH2CH2CN,
each R10 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, halo, D, CN, ORa10, C(O)NRc10Rd10, and NRc10Rd10; wherein said C1-3 alkyl and C3-6cycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R9;
each R11 is independently selected from C1-2 alkyl, C1-2 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, halo, D, CN, ORa11, and NRc11Rd11; wherein said C12 alkyl, C3-6 cycloalkyl, and 4-6 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from Rg;
each R21 is independently selected from C1-3 alkyl, C1-3 haloalkyl, halo, D, and CN;
each R30 is independently selected from C1-3 alkyl, C1-3 haloalkyl, 4-10 membered heterocycloalkyl, halo, D, CN, ORa30, C(O)NRc30Rd30, and NRc30Rd30; wherein said C1-3 alkyl and 4-10 membered heterocycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R31;
each R31 is independently selected from C1-3 alkyl, C1-3 haloalkyl, halo, D, and CN;
each R60 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, ORa60, C(O)Rb60, C(O)NR60Rd60, and NRc60Rd60; wherein said C1-3 alkyl, C3-6cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R61;
each R61 is independently selected from C1-3 alkyl, C1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, CN, ORa61, C(O)Rb61, and NRc61Rd61;
each R70 is independently selected from C1-3 alkyl, C1-3 haloalkyl, phenyl, 5-6 membered heteroaryl, halo, D, and CN;
each Ra3 is independently selected from H, C1-3 alkyl, C1-3 haloalkyl, 5-6 membered heteroaryl, and phenyl; wherein said C1-3 alkyl, 5-6 membered heteroaryl, and phenyl are each optionally substituted with 1 or 2 substituents independently selected from R30;
each Ra7, Rc7 and Rd7 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl; wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R70;
each Ra10, Rc10 and Rd10 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
each Ra11, Rc11 and Rd11, is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
Rb20 is selected from NH2, C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each Ra21, Rc21 and Rd21 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
each Ra30, Rc30 and Rd30 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl;
each Ra60, Rb60, Rc60 and Rd60 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl; wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R61;
or any Rc60 and Rd60 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 R61;
each Ra61, Rb61 Rc61 and Rd61 is independently selected from H, C1-3 alkyl, and C1-3 haloalkyl; and
each Rg is independently selected from D, OH, CN, halo, C1-2 alkyl, amino, and C1-2 haloalkyl.

### Claim 4 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein:
XY is selected from —NR5—C(═O)—, —N═N—, and —N═CR6—;
R1 is selected from H, and C1-2 alkyl; wherein said C1-2 alkyl is optionally substituted with 1 or 2 substituents independently selected from R11;
Cy1 is selected from C3-10 cycloalkyl, C6-10 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 C3-10 cycloalkyl, C6-10 aryl and 6-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R10;
R4 is selected from ORa3;
R5 is H;
R7 is selected from phenyl, 5-6 membered heteroaryl, F, and ORa7; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R70;
Cy2 is selected from
when Cy2 is Cy2-a and XY is —N═CR6—, then, R6 is H;
when Cy2 is Cy2-a, then R2 is Cl;
when Cy2 is Cy2-b and XY is —N═CR6—, then R6 is selected from C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-10 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R60;
when Cy2 is Cy2-b, then R2 is selected from H, C1-2 alkyl, —CH2CH2CN,
each R10 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, halo, CN, ORa10, and NRc10Rd10; wherein said C1-3 alkyl and C3-6 cycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from R9;
each R11 is independently selected from 4-6 membered heterocycloalkyl, and ORa11;
wherein said 4-6 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from Rg;
each R21 is CN;
each R30 is independently selected from 4-10 membered heterocycloalkyl and C(O)NRc30Rd30; wherein said 4-10 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from R31;
each R31 is independently selected from C1-3 alkyl;
each R60 is independently selected from C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, 5-6 membered heteroaryl, C(O)Rb60, C(O)NRc60Rd60, and NRc60Rd60; wherein said C1-3 alkyl, C3-6 cycloalkyl, 4-6 membered heterocycloalkyl, phenyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R61;
each R61 is independently selected from phenyl, 5-6 membered heteroaryl, and C(O)Rb61;
each R70 is independently selected from phenyl, 5-6 membered heteroaryl, and CN;
each Ra3 is independently selected from C1-3 alkyl, and phenyl; wherein said C1-3 alkyl and phenyl are each optionally substituted with 1 or 2 substituents independently selected from R30;
each Ra7 is C1-3 alkyl; wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R70;
each Ra10, Rc10 and Rd10 is H;
each Ra11 is H;
Rb20 is selected from NH2, C1-3 alkyl, C3-6cycloalkyl, and 5-6 membered heteroaryl; wherein said C1-3 alkyl, C3-6 cycloalkyl, and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R21;
each Rc30 and Rd30 is independently selected from H and C1-3 alkyl;
each Rb60, Rc60 and Rd60 is independently selected from H and C1-3 alkyl; wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R61;
or any Rc60 and Rd60 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 R61;
each Rb61 is C1-3 alkyl; and
each Rg is CN.

### Claim 5 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein XY is —NR5—C(═O)— or —N═N—.

### Claim 6 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein XY is —N═CR6—.

### Claim 7 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is H.

### Claim 8 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Cy1 is selected from C6-10 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 C6-10 aryl and 6-10 membered heteroaryl are each optionally substituted with 1, 2, or 3 substituents independently selected from R10.

### Claim 9 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Cy1 is selected from

### Claim 10 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from

### Claim 11 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R4 is selected from H, C1-3 alkyl, C1-3 haloalkyl, 5-10 membered heteroaryl, ORa3, and NRc3Rj3; wherein said C1-3 alkyl and 5-10 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R30.

### Claim 12 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R7 is selected from phenyl, 5-6 membered heteroaryl, F and ORa7; wherein said phenyl and 5-6 membered heteroaryl are each optionally substituted with 1 or 2 substituents independently selected from R70.

### Claim 13 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein when Cy2 is Cy2-a and XY is —N═CR6—, then, R6 is H.

### Claim 14 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein when Cy2 is Cy2-a, then R2 is Cl.

### Claim 15 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein when Cy2 is Cy2-b and XY is —N═CR6—, then R6 is selected from C1-3 alkyl, and C1-3 haloalkyl; wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R60.

### Claim 16 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein when Cy2 is Cy2-b, then R2 is selected from H, C1-2 alkyl, —CH2CH2CN,

### Claim 17 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R10 is independently selected from C1-3 alkyl, C1-3 haloalkyl, C3-6 cycloalkyl, halo, CN, ORa10, and NRc10Rd10; wherein said C1-3 alkyl and C3-6cycloalkyl are each optionally substituted with 1 or 2 substituents independently selected from Rg.

### Claim 18 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R11 is independently selected from 4-6 membered heterocycloalkyl and ORa11, wherein said 4-6 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from Rg.

### Claim 19 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R21 is independently selected from halo, CN, and ORa21.

### Claim 20 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R30 is independently selected from 4-10 membered heterocycloalkyl and C(O)NRc30Rd30; wherein said 4-10 membered heterocycloalkyl is optionally substituted with 1 or 2 substituents independently selected from R31.

### Claim 21 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R31 is independently selected from C1-3 alkyl and C1-3 haloalkyl.

### Claim 22 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R60 is independently selected from C1-3 alkyl, C(O)NRc60Rd60, and NRc60Rd60; wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R61.

### Claim 23 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R61 is independently selected from phenyl, 5-6 membered heteroaryl, and C(O)Rb61.

### Claim 24 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each R70 is independently selected from phenyl, 5-6 membered heteroaryl, and CN.

### Claim 25 (depends on 1)

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

### Claim 26 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each Ra3 is independently selected from C1-3 alkyl; wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R30.

### Claim 27 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Rb20 is selected from NH2 and C1-3 alkyl; wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R21.

### Claim 28 (depends on 1)

The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein each Rb60, Rc60 and Rd60 is independently selected from H and C1-3 alkyl; wherein said C1-3 alkyl is optionally substituted with 1 or 2 substituents independently selected from R61; or any Rc60 and Rd60 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 R61.

### Claim 29 (depends on 1)

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.

### Claim 30 (depends on 1)

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

### Claim 31 (depends on 1)

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

### Claim 32 (depends on 1)

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.

### Claim 33 (depends on 1)

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.

### Claim 34 (depends on 1)

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.