Quinazoline compounds

Patent metadata

Field	Value
Publication number	US-9730936-B2
Application number	US-201514998042-A
Country	US
Kind code	B2
Filing date	Dec 23, 2015
Priority date	Dec 24, 2014
Publication date	Aug 15, 2017
Grant date	Aug 15, 2017

Abstract

Described herein are compounds of Formula (I) and tautomers and pharmaceutical salts thereof, compositions and formulations containing such compounds, and methods of using and making such compounds.

First claim

What is claimed is:

1. A compound of formula (I):

wherein
Q is

X 1 , X 2 , and X 3 are each independently N or C(R 11 ), provided that, at most 2 of X 1 , X 2 , and X 3 are N;
R 1 is —H, —CN, —OR a , —C(O)OR a , halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or C 1-6 heteroalkyl, wherein each C 1-6 alkyl, C 3-10 cycloalkyl, and C 1-6 heteroalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12 groups, which may be same or different;
R 2 is —CN;
R 3 is —H, —OR a , —SR a , —NR a R b , —NHC(O)NR a R b , C 1-6 alkyl, C 3-10 cycloalkyl, or C 1-6 heteroalkyl, wherein each C 1-6 alkyl, C 3-10 cycloalkyl, and C 1-6 heteroalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12 groups, which may be same or different;
R 4 is —H or —OR a ;
R 5 is —H, —OR a , halogen, —NO 2 , —CN, —NR a R b , —NHC(O)NR a R b , —OC(O)NR a R b , —CH 2 C(O)NR a R b , C 1-6 alkyl, C 3-10 cycloalkyl, or C 1-6 heteroalkyl, wherein each C 1-6 alkyl, C 3-10 cycloalkyl, and C 1-6 heteroalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12 groups, which may be same or different;
R 6 is —H;
R 7 is C 1-6 alkyl, halogen, or —OR a ;
R 8 is C 1-6 alkyl, halogen, or —OR a ;
R 9 is —H, C 1-6 alkyl, or C 3-10 cycloalkyl, wherein each C 1-6 alkyl and C 3-10 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12 groups, which may be same or different;
R 10 is —H, C 1-6 alkyl, or C 3-10 cycloalkyl, wherein each C 1-6 alkyl and C 3-10 cycloalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12 groups, which may be same or different;
each R 11 is independently —H, —CN, —OR a , —C(O)OR a , halogen, C 1-6 alkyl, C 3-10 cycloalkyl, or C 1-6 heteroalkyl, which may be same or different, wherein each C 1-6 alkyl, C 3-10 cycloalkyl, and C 1-6 heteroalkyl is optionally substituted with 1, 2, 3, 4, or 5 R 12 groups, which may be same or different;
each R 12 is independently C 1-6 alkyl, C 3-10 cycloalkyl, C 1-6 heteroalkyl, 5-10 membered heterocyclyl, C 6-10 aryl, 5-10 membered heteroaryl, halogen, —OR a , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —OC(O)NR a R b , —NR a C(O)OR b , —SR a , —S(O) 1-2 R a , —S(O) 2 F, —S(O) 2 NR a R b , —NR a S(O) 2 R b , —N 3 , —CN, or —NO 2 ; wherein each C 1-6 alkyl, C 3-10 cycloalkyl, C 1-6 heteroalkyl, and 5-10 membered heterocyclyl is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from halogen, —OR a , —C(O)R a , —C(O)OR a , —C(O)NR a R b , —OC(O)NR a R b , —NR a C(O)OR b , —SR a , —S(O) 1-2 R a , —S(O) 2 F, —S(O) 2 NR a R b , —NR a S(O) 2 R b , —N 3 , —CN, and —NO 2 , groups, which may be same or different;
each R a and R b is independently —H, —NH 2 , C 1-6 alkyl, C 3-10 cycloalkyl, C 1-6 heteroalkyl, 5-10 membered heterocyclyl, C 6-10 aryl, or 5-10 membered heteroaryl, wherein each C 1-6 alkyl, C 3-10 cycloalkyl, C 1-6 heteroalkyl, 5-10 membered heterocyclyl, C 6-10 aryl, and 5-10 membered heteroaryl is optionally substituted with 1, 2, 3, 4, or 5 R 13 groups, which may be same or different; or R a and R b together with the atoms to which they are attached form a 5-10 membered heterocycle; and
each R 13 is independently —CN, halogen, C 1-6 alkyl, C 3-10 cycloalkyl, C 1-6 heteroalkyl, or 5-10 membered heterocyclyl,
or a tautomer or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein Q is

3. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein X 1 , X 2 , and X 3 are each CH.

4. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein X 1 is N; X 2 is CH; and X 3 is CH.

5. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein X 1 , X 2 , and X 3 are C(R 11 ); each R 11 are independently selected from —H, —CN, —OR a , halogen, and C 1-6 alkyl; and R 1 is selected from —H, —CN, —OR a , halogen, and C 1-6 alkyl.

6. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R 3 is —H, —OR a , —NR a R b , —NHC(O)NR a R b , C 1-6 alkyl, or C 1-6 heteroalkyl.

7. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R 3 is —NH 2 or —OH.

8. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R 4 is —H and R 5 is —H, —OR a , halogen, —NO 2 , —CN, —NR a R b , —NHC(O)NR a R b , or C 1-6 alkyl.

9. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R 4 and R 5 are —H.

10. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R 7 is C 1-6 alkyl.

11. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R 8 is C 1-6 alkyl.

12. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R 7 and R 8 are C 1-6 alkyl.

13. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R 7 and R 8 are methyl.

14. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R 9 is —H or C 1-6 alkyl.

15. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, wherein R 10 is —H or C 1-6 alkyl.

16. The compound of claim 1 , or a tautomer or a pharmaceutically acceptable salt thereof, Q is selected from

17. A compound of claim 1 , wherein the compound is selected from the group consisting of:

Structure
Compound ID

 1;

 2;

 3;

Assignees

• Gilead Sciences Inc
• Inst Of Organic Chemistry And Biochemistry Of The As Cr V V I

Inventors

• Baszczy{Hacek Over (N)}Ski Ond{Hacek Over (R)}Ej
• Dejmek Milan
• Hu Yunfeng Eric
• Jansa Petr
• Lansdon Eric
• Mackman Richard L
• {Hacek Over (S)}Imon Petr

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/18

  for HIV · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D239/95

  with hetero atoms directly attached in positions 2 and 4 · CPC title