RAS inhibitors and methods of using the same

1 . A compound of formula (I):

or a pharmaceutically acceptable salt thereof,

wherein:

ring A is a 4-12 membered heterocyclic ring, optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, cyano, oxo, C 1-4 -alkyl, C 2-4 -alkynyl, C 1-4 -heteroalkyl, C 3-8 -cycloalkyl, -C 0-4 -alkyl-C(O)N(R 6d ) 2 , and —C 0-4 -alkyl-C(O)OR 6d ;

and/or wherein two substituents on the same atom of ring A may form a 3- to 5-membered ring together with the carbon atom on which they are attached;

and/or wherein two substituents on adjacent atoms of ring A may form a 3- to 6-membered ring together with the carbon atoms on which they are attached;

wherein the C 1-4 -alkyl, C 2-4 -alkynyl, C 1-4 -heteroalkyl or C 3-8 -cycloalkyl may be optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, —OR 6d , cyano, and oxo;

R 1 is selected from the group consisting of

L is selected from the group consisting of a direct bond, -N(R 6d )-, -C(O)N(R 6d )—, —S(O 2 )N(R 6d )-, and —O—;

R 2a is a direct bond, C 1-4 -alkylene, C 1-4 -heteroalkylene, C 3-8 -cycloalkylene, 3- to 8-membered heterocycloalkylene, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C 1-4 -alkylene, C 1-4 -heteroalkylene, C 3-8 -cycloalkylene, 3- to 8-membered heterocycloalkylene, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl each is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, -OR 6d , oxo, cyano, C 3-8 -cycloalkyl, C 1-4 -alkyl, C 1-4 -heteroalkyl, and 3- to 8-membered heterocycloalkyl;

Y is selected from the group consisting of a direct bond, unsubstituted or substituted C 1-4 -alkyl, unsubstituted or substituted C 1-4 -alkylene, unsubstituted or substituted C 1-4 -heteroalkyl, —N(R 6d )—, —NR 6d C(O)—, —C(O)NR 6d —, —NR 6d C(O)NR 6d —, -S(O 2 )NR 6d —, and —NR 6d S(O) 2 —;

R 2b is H, C 1-4 -alkyl, C 1-4 -heteroalkyl, C 3-8 -cycloalkyl, 3- to 8-membered heterocycloalkyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C 1-4 -alkyl, C 1-4 -heteroalkyl, C 3-8 -cycloalkyl, 3- to 8-membered heterocycloalkyl, 6- to 10-membered aryl, or 5-to 10-membered heteroaryl is each optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, —OR 6d , oxo, cyano, -N(R 6d ) 2 , C 3-8 -cycloalkyl, C 1-4 -alkyl, C 1-4 -heteroalkyl, and 3- to 8-membered heterocycloalkyl;

R 3 is

R 4 is H, C 1-6 -alkyl, C 1-6 -heteroalkyl, C 1-6 -haloalkyl, C 3-8 -cycloalkyl, 3- to 8-membered heterocycloalkyl, —OC 1-6 -haloalkyl, —NH(C 1-6 -alkyl), or —N(C 1-6 -alkyl) 2 , wherein the C 1-6 -alkyl, C 1-6 -heteroalkyl, C 1-6 -haloalkyl, C 3-8 -cycloalkyl, 3- to 8-membered heterocycloalkyl, or —OC 1-6 -haloalkyl is each optionally substituted with one or more substituents selected from the group consisting of C 1-4 -alkyl, C 1-4 -heteroalkyl, halo, cyano, hydroxyl, ether, —N(R 6d ) 2 , and C 3-8 -cycloalkyl, 3- to 8-membered heterocycloalkyl,

R 5 is H, C 1-6 -alkyl, C 1-6 -heteroalkyl, C 3-8 -cycloalkyl, 3- to 8-membered heterocycloalkyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, wherein the C 1-6 -alkyl, C 1-6 -heteroalkyl, C 3-8 -cycloalkyl, 3- to 8-membered heterocycloalkyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl is each optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, carboxyl, cyano, —OR 6d , —N(R 6d ) 2 , C 3-8 -cycloalkyl, C 1-4 -alkyl, C 1-4 -heteroalkyl, 3- to 8-membered heterocycloalkyl, 6-membered aryl, and 5- to 6-membered heteroaryl, or an R 5 and R 7 taken together with the atom to which they are attached form a 5- or 6-membered monocyclic ring system or a bicyclic system, wherein the bicyclic system is a 9- or 10-membered heterocyclic ring system;

R 6 , R 6a and R 6b are each independently H, halo, cyano, C 1-6 -alkyl, C 1-6 -heteroalkyl, C 3-8 -cycloalkyl, 3- to 8-membered heterocycloalkyl, C 3-8 -aryl, or C 3-8 -heteroaryl, wherein the C 1-6 -alkyl, C 1-6 -heteroalkyl, C 3-8 -cycloalkyl, 3- to 8-membered heterocycloalkyl, C 3-8 -aryl, or C 3-8 -heteroaryl each is optionally substituted with one or more substituents selected from halo, hydroxy, cyano, —N(R 6d ) 2 , —OR 6d , C 1-4 -alkyl, 3- to 8-membered heterocycloalkyl, and C 1-4 -heteroalkyl;

R 6c is H, halo, cyano, C 1-6 -alkyl, C 1-6 -heteroalkyl, C 3-8 -cycloalkyl, or 3- to 8-membered heterocycloalkyl, wherein the C 1-6 -alkyl, C 1-6 -heteroalkyl, C 3-8 -cycloalkyl, or 3- to 8-membered heterocycloalkyl is each optionally substituted with one or more substituents selected from halo, cyano, —OR 6d , hydroxy, and C 1-4 -heteroalkyl;

R 6d is independently at each occurrence selected from the group consisting of H, cyano, C 1-6 -alkyl, C 1-6 -heteroalkyl, C 3-8 -cycloalkyl, and 3- to 8-membered heterocycloalkyl; and

R 7 is H, C 1-6 -alkyl, C 1-6 -heteroalkyl, or C 3-8 -cycloalkyl, wherein the C 1-6 -alkyl, C 1-6 -heteroalkyl, or C 3-8 -cycloalkyl is each optionally substituted with one or more substituents selected from the group consisting of halo, cyano, hydroxyl, carboxyl, —OR 6d , —N(R 6d ) 2 , C 3-8 -cycloalkyl, C 1-4 -alkyl, C 1-4 -heteroalkyl, and 3- to 8-membered heterocycloalkyl.

2 . The compound of claim 1 , wherein ring A is a 6- or 7-membered heterocyclic ring, optionally substituted with one or more substituents selected from the group consisting of halo, hydroxyl, C 1-4 -alkyl, and C 1-4 -heteroalkyl, wherein the C 1-4 -alkyl and C 1-4 -heteroalkyl are optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, and cyano.

3 . The compound of claim 1 , wherein ring A is selected from the group consisting of:

wherein the * indicates a bond between the nitrogen atom of ring A containing the* and R 1 ; and the ** indicates a bond between the nitrogen atom of ring A containing the ** and the pyrimidyl group of formula (I);

or wherein the * indicates a bond between the nitrogen atom of ring A containing the* and the pyrimidyl group of formula (I); and the ** indicates a bond between the nitrogen atom of ring A containing the * and R 1 .

4 . The compound of claim 3 , wherein ring A is

wherein the * indicates a bond between the nitrogen atom of ring A containing the * and R 1 ; and the ** indicates a bond between the nitrogen atom of ring A containing the ** and the pyrimidyl group of formula (I).

5 . The compound of claim 3 , wherein R 1 is

6 . The compound of claim 5 ,

wherein R 1 is

7 . The compound of claim 5 , wherein L is selected from the group consisting of a direct bond, —N(R 6d )—, and —O—.

8 . The compound of claim 7 , wherein L is —N(R 6d )— or —O—.

9 . The compound of claim 8 , wherein Rod is H or C 1-6 alkyl.

10 . The compound of claim 9 , wherein R 2a is selected from the group consisting of C 1-6 alkyl, 3- to 8-membered heterocycloalkyl and 5- to 6-membered heteroaryl.

11 . The compound of claim 10 , wherein Y is selected from the group consisting of a direct bond, —N(R 6d )—, and —O—.

12 . The compound of claim 11 , wherein R 2b is selected from the group consisting of H, C 1-4 -alkyl, C 1-4 -heteroalkyl, 5- to 6-membered heterocycloalkyl and 5-to 6-membered heteroaryl.

13 . The compound of claim 12 , wherein -L-R 2a -Y-R 2b is selected from the group consisting of:

14 . The compound of claim 12 , wherein R 3 is

wherein R 5 is 6- to 10-membered aryl or 5- to 10-membered heteroaryl, and R 7 is H or C 1-6 alkyl.

15 . The compound of claim 14 , wherein R 3 is selected from the group consisting of:

16 . The compound of claim 1 , wherein R 4 is H, halo, C 1-6 -alkyl, C 1-3 haloalkyl, —OC 1-6 alkyl, —OCC 1-3 haloalkyl, —CH 2 —OC 1-6 alkyl, —NH(C 1-6 -alkyl) or —N(C 1-6 -alkyl) 2 .

17 . The compound of claim 16 , wherein R 4 is H.

18 . The compound of claim 1 , wherein the compound of formula (I) is selected from the group consisting of: