Imidazopyrimidine derivatives

Patent metadata

Field	Value
Publication number	US-11179397-B2
Application number	US-201916591092-A
Country	US
Kind code	B2
Filing date	Oct 2, 2019
Priority date	Oct 3, 2018
Publication date	Nov 23, 2021
Grant date	Nov 23, 2021

Abstract

The present disclosure provides a compound of Formula (I):

or a pharmaceutically acceptable salt thereof as described herein. The present disclosure also provides pharmaceutical compositions comprising a compound of Formula I, processes for preparing compounds of Formula I, therapeutic methods for treating cancers.

First claim

What is claimed is:

1. A compound having formula (VII):

or a pharmaceutically acceptable salt; wherein:
A is selected from C 6-10 aryl, 5-10 membered heteroaryl, C 3-12 cycloalkyl, and 4-12 membered heterocyclyl; each A is optionally substituted with one to six R A independently selected from halo, cyano, hydroxyl, azido, nitro, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, C 1-4 alkylene-OH, oxo, ═NR a1 , —SR a1 , —OR a1 , —NR a1 R a2 , —COR a2 , —CONR a1 R a2 , —COOR a2 , —N(R a2 )—C(O)R a2 , —N(R a2 )—C(O)OR a2 , —N(R a2 )—C(O)—NR a2 R a2 , —N(R a2 )—SO 2 R a2 , —SO 2 R a2 , —SO 2 OR a2 , —SO 2 NR a1 R a2 , —O—SO 2 —NR a1 R a2 , —O(CO)—N—R a1 R a2 , C 3-8 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, —C 1-4 alkylene-C 3-8 cycloalkyl, —C 1-4 alkylene-(3-8 membered heterocyclyl), —C 1-4 alkylene-C 6-10 aryl, and —C 1-4 alkylene-(5-10 membered heteroaryl);
wherein the C 3-8 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, —C 1-4 alkylene-C 3-8 cycloalkyl, —C 1-4 alkylene-(3-8 membered heterocyclyl), —C 1-4 alkylene-C 6-10 aryl, and —C 1-4 alkylene-(5-10 membered heteroaryl) of R A are independently optionally substituted with one to three groups selected from halo, cyano, hydroxyl, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxyl, and C 1-4 alkylene-OH;
wherein the 5-10 membered heteroaryl of A, and R A contains one to five heteroatoms independently selected from S, N, and O, and optionally comprises one to three C(O) or one S(O) 2 ;
L is selected from a bond, —S—, and —O—;
Z 1 and Z 2 are independently selected from N and CR 3 ; wherein R 3 is selected from H, halo, hydroxyl, cyano, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxyl, C 1-4 alkylene-OH, —NR c1 R c2 , —C(O)OR c1 , C 6-10 aryl, and 5-10 membered heteroaryl; wherein each C 6-10 aryl, and 5-10 membered heteroaryl of R 3 is independently optionally substituted with one to three groups independently selected from halo, hydroxyl, cyano, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxyl, —N(R c1 )—SO 2 R c1 , and —SO 2 R c1 ;
R 1 is selected from H, halo, —NR c1 R c2 , C 1-4 alkyl, and C 1-4 haloalkyl;
each R 2 is independently selected from halo, cyano, nitro, —O—C 1-6 alkyl, oxo, —NR c1 R c2 , —(SO v )—R c1 , —NR c1 (SO v )—R c1 , —C(O)OR c1 , —C(O)—NR c1 R c2 , —S(O 2 )—NR c1 R c2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alklene-OH, —C 1-4 alkylene-NR c1 R c2 , C 3-8 cycloalkyl, 3-6 membered heterocyclyl, —O—C 3-8 cycloalkyl, —O-(3-6 membered heterocyclyl), C 6-10 aryl, and 5-10 membered heteroaryl;
each R 22 is independently selected from halo, —NR c1 R c2 , hydroxyl, azido, cyano, oxo, —C(O)OR c1 , C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxyl, C 1-4 alkylene-NR c1 R c2 , —C 1-4 alkylene-O—C 1-4 alkyl, —C 1-4 alkylene-OH, —CO—NR c1 R c2 , —C(O)OR c1 , —N(R c1 )—C(O)R c1 , —N(R c1 )—C(O)OR c1 , —N(R c1 )—C(O)—NR c1 R c2 , —N(R c1 )—(SO v )R c1 , —SO 2 R c1 , —SO 2 OR c1 , —SO 2 R c1 R c2 , C 3-8 cycloalkyl, 3-6 membered heterocyclyl, C 6-10 aryl, and 5-10 membered heteroaryl;
each X 3 , X 4 , X 5 , and X 6 is independently selected from CR xx , and N; wherein R xx is selected from H, halo, cyano, hydroxyl, azido, nitro, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxyl, C 1-4 alkylene-OH, —SR a1 , —OR a1 , —NR a1 R a2 , —COR a2 , —CONR a1 R a2 , —COOR a2 , —N(R a2 )—C(O)R a2 , —N(R a2 )—C(O)OR a2 , —N(R a2 )—C(O)—NR a2 R a2 , —N(R a2 )—SO 2 R a2 , —SO 2 R a2 , —SO 2 OR a2 , —SO 2 R a1 R a2 , —O—SO 2 —NR a1 R a2 , —O(CO)—NR a1 R a2 , C 3-8 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, —C 1-4 alkylene-C 3-8 cycloalkyl, —C 1-4 alkylene-(3-8 membered heterocyclyl), —C 1-4 alkylene-C 6-10 aryl, and —C 1-4 alkylene-(5-10 membered heteroaryl);
R a1 is selected from H, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkylene-OH, C 1-4 alkylene-COOR a2 , —C 1-4 alkylene-C 1-4 alkoxyl, and —C(O)—NH 2 ;
R a2 is selected from H, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkylene-OH, C 3-8 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl, and 5-10 membered heteroaryl; wherein the C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkylene-OH, C 3-8 cycloalkyl, 3-8 membered heterocyclyl, C 6-10 aryl, and 5-6 membered heteroaryl of R a2 are independently optionally substituted with one to three groups selected from halo, cyano, hydroxyl, —COOR a3 , C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkylene-OH, and C 1-4 alkoxyl; wherein R a3 is selected from H, C 1-4 alkyl, and C 1-4 haloalkyl;
R c1 and R c2 are independently selected from H, C 1-6 alkyl, and C 1-6 haloalkyl; wherein each of the C 1-6 alkyl and C 1-6 haloalkyl of R c1 and R c2 is optionally substituted with one or two groups selected from C 1-4 alkoxyl, and C 1-4 alklene-OH;
v is selected from 0, 1, and 2;
m is selected from 0, 1, 2, 3, and 4; and
q is selected from 0, 1, 2, 3, and 4.

2. The compound of claim 1 , or a pharmaceutically acceptable salt, wherein L is —S—.

3. The compound of claim 1 , or a pharmaceutically acceptable salt, wherein R A is independently selected from F, Cl, —CH 3 , —CF 3 , and —NH 2 .

4. The compound of claim 1 , or a pharmaceutically acceptable salt, wherein R 1 is selected from H, halo, and C 1-4 alkyl.

5. The compound of claim 1 , or a pharmaceutically acceptable salt, wherein R 1 is selected from Cl and —CH 3 .

6. The compound of claim 1 , or a pharmaceutically acceptable salt, wherein Z 1 and Z 2 are CH.

7. The compound of claim 1 , wherein q is 1 or 2.

8. The compound of claim 1 , wherein p is selected from 0, 1, and 2.

9. The compound of claim 1 , wherein X 3 , X 4 , X 5 , and X 6 are each CH.

10. The compound of claim 1 , wherein each R 22 is selected from CH 3 , CH 2 NH 2 , NH 2 , and OH.

11. The compound of claim 1 , selected from:

12. A compound having the structure:

13. A pharmaceutical composition comprising a compound of claim 1 and at least one pharmaceutically acceptable carrier.

Assignees

• Gilead Sciences Inc

Inventors

• Chin Gregory
• Clarke Michael O' Neil Hanrahan
• Han Xiaochun
• Hansen Tim
• Hu Yunfeng Eric
• Koltun Dmitry
• Mcfadden Ryan
• Mish Michael R
• Parkhill Eric Q
• Sperandio David
• Xu Lianhong
• Yang Hai

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D519/00

  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 · CPC title

• A61K31/519 Primary

  ortho- or peri-condensed with heterocyclic rings · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P35/00

  Antineoplastic agents · CPC title