Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication

Patent metadata

Field	Value
Publication number	US-10407410-B2
Application number	US-201716094536-A
Country	US
Kind code	B2
Filing date	May 9, 2017
Priority date	May 11, 2016
Publication date	Sep 10, 2019
Grant date	Sep 10, 2019

Abstract

Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.

First claim

We claim:

1. A compound of Formula I

or a pharmaceutically acceptable salt thereof wherein:
R 1 is selected from hydrogen, C 1-6 alkyl, C 3-7 cycloalkyl, or hydroxyC 1-6 alkyl;
R 2 is selected from indanyl, tetrahydronaphthalinyl, indolyl, indolinyl, isoindolinyl, isoindolinonyl, benzofuranyl, benzothiophenyl, benzoimidazolonyl, chromanyl, quinolinyl, quinolinonyl, isoquinolinyl, tetrahydroisoquinolinonyl, dihydrobenzodioxinyl or benzoxazinyl, and is substituted with 0-1 R 6 substituent and 0-3 halo or C 1-6 alkyl substituents;
R 3 is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, or homomorpholinyl, and is substituted with 0-3 substituents selected from cyano, halo, C 1-6 alkyl, haloC 1-6 alkyl, C 1-6 alkoxy, and haloC 1-6 alkoxy;
R 4 is selected from C 1-6 alkyl or haloC 1-6 alkyl;
R 5 is C 1-6 alkyl;
R 6 is selected from (Ar 1 )C 1-6 alkyl, ((Ar 1 )O)C 1-6 alkyl, (Ar 1 )C 2-10 alkenyl, hydroxy, C 1-6 alkoxy, (Ar 1 )O, (Ar 1 )SO 2 , (Ar 1 )CO, carboxy, or Ar 1 ; wherein Ar 1 is selected from phenyl, pyridinyl, or thiazolyl, and is substituted with 0-3 substituents selected from cyano, halo, C 1-6 alkyl, haloC 1-6 alkyl, C 1-6 alkoxy, and haloC 1-6 alkoxy;
or a pharmaceutically acceptable salt thereof.

2. A compound or salt of claim 1 wherein R 2 is selected from tetrahydronaphthalinyl, isoindolinyl, isoindolinonyl, chromanyl, quinolinyl, quinolinonyl, isoquinolinyl and tetrahydroisoquinolinonyl, and is substituted with 0-1 R 6 substituent and 0-3 halo or C 1-6 alkyl substituents.

3. A compound or salt of claim 2 where R 2 is chromanyl substituted with 0-1 R 6 substituent and 0-3 halo or C 1-6 alkyl substituents.

4. A compound or salt of claim 1 where R 2 has 1 R 6 substituent and 0-3 halo or C 1-6 alkyl substituents.

5. A compound or salt of claim 1 where R 3 is piperidinyl substituted with 0-3 substituents selected from cyano, halo, C 1-6 alkyl, haloC 1-6 alkyl, C 1-6 alkoxy, and haloC 1-6 alkoxy.

6. A compound or salt of claim 1 where R 6 is selected from (Ar 1 )C 1-6 alkyl, ((Ar 1 )O)C 1-6 alkyl, (Ar 1 )C 2-10 alkenyl.

7. A compound or salt of claim 1 where R 6 is selected from hydroxy, alkoxy, (Ar 1 )O, (Ar 1 )SO 2 , (Ar 1 )CO, or carboxy.

8. A composition useful for treating HIV infection comprising a compound or salt of claim 1 and a pharmaceutically acceptable carrier.

9. The composition of claim 8 further comprising a therapeutically effective amount at least one other agent used for treatment of AIDS or HIV infection selected from nucleoside HIV reverse transcriptase inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, HIV protease inhibitors, HIV fusion inhibitors, HIV attachment inhibitors, CCR5 inhibitors, CXCR4 inhibitors, HIV budding or maturation inhibitors, and HIV integrase inhibitors, and a pharmaceutically acceptable carrier.

10. The composition of claim 9 wherein the other agent is dolutegravir.

11. A method for treating HIV infection comprising administering a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

12. The method of claim 11 further comprising administering a therapeutically effective amount of at least one other agent used for treatment of AIDS or HIV infection selected from nucleoside HIV reverse transcriptase inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, HIV protease inhibitors, HIV fusion inhibitors, HIV attachment inhibitors, CCR5 inhibitors, CXCR4 inhibitors, HIV budding or maturation inhibitors, and HIV integrase inhibitors.

13. The method of claim 12 wherein the other agent is dolutegravir.

Assignees

• Viiv Healthcare Uk No 5 Ltd

Inventors

• Kadow John F
• Naidu B Narasimhulu
• Patel Manoj
• Walker Michael A
• Wang Tao
• Yin Zhiwei
• Zhang Zhongxing
• Zheng Zhizhen Barbara

Classifications

• C07D407/14

  containing three or more hetero rings · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title

• A61K31/4725

  containing further heterocyclic rings · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• A61K31/4709

  Non-condensed quinolines and containing further heterocyclic rings · CPC title