Imidazo[1,2-a]pyridine derivatives for use as inhibitors of human immunodeficiency virus replication

Patent metadata

Field	Value
Publication number	US-2018222901-A1
Application number	US-201515505955-A
Country	US
Kind code	A1
Filing date	Aug 25, 2015
Priority date	Aug 27, 2014
Publication date	Aug 9, 2018
Grant date	—

Abstract

The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

First claim

We claim:

1 . A compound of Formula I

where:
R 1 is phenyl substituted with 1 Ar 1 substituent and also substituted with 0-3 substituents selected from halo, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, and alkenyloxy;
R 2 is hydrogen or alkyl;
R 3 is azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, or homomorpholinyl, and is substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, alkenyloxy, and phenyl;
or R 3 is cycloalkyl, cycloalkenyl, phenyl, chromanyl, oxazinyl, or dihydropyranoquinolinyl, and is substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, alkenyloxy, and phenyl;
R 4 is alkyl or haloalkyl;
R 5 is hydrogen or alkyl;
R 6 is hydrogen or alkyl;
Ar 1 is phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, furanyl, thienyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, or tetrazolyl, and is substituted with 0-3 substituents selected from halo, cyano, alkyl, haloalkyl, benzyl, alkoxy, haloalkoxy, alkenyloxy, and benzyloxy;
or a pharmaceutically acceptable salt thereof.

2 . A compound of claim 1 where:
R 1 is phenyl substituted with 1 Ar 1 substituent;
R 2 is hydrogen;
R 3 is piperidinyl substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, alkenyloxy, and phenyl;
or R 3 is phenyl, chromanyl, or dihydropyranoquinolinyl, and is substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, alkenyloxy, and phenyl;
R 4 is alkyl;
R 5 is alkyl;
R 6 is hydrogen;
Ar 1 is phenyl or pyrazolyl, and is substituted with 0-3 substituents selected from halo, cyano, alkyl, haloalkyl, benzyl, alkoxy, haloalkoxy, alkenyloxy, and benzyloxy;
or a pharmaceutically acceptable salt thereof.

3 . A compound of claim 1 where R 1 is phenyl substituted with 1 Ar 1 substituent.

4 . A compound of claim 1 where R 2 is hydrogen, R 4 is alkyl, R 5 is alkyl, and R 6 is hydrogen.

5 . A compound of claim 1 where R 3 is piperidinyl substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, alkenyloxy, and phenyl.

6 . A compound of claim 1 where R 3 is phenyl, chromanyl, or dihydropyranoquinolinyl, and is substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, alkenyl, cycloalkyl, hydroxy, alkoxy, haloalkoxy, alkenyloxy, and phenyl.

7 . A compound of claim 1 where Ar 1 is phenyl, pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, and is substituted with 0-3 substituents selected from halo, cyano, alkyl, haloalkyl, benzyl, alkoxy, haloalkoxy, alkenyloxy, and benzyloxy.

8 . A compound of claim 1 where Ar 1 is phenyl substituted with 0-3 substituents selected from halo, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyloxy, and benzyloxy.

9 . A compound of claim 1 where Ar 1 is pyrrolyl, furanyl, thienyl, pyrazolyl, isoxazolyl, isothiazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, or tetrazolyl, and is substituted with 0-3 substituents selected from halo, cyano, alkyl, haloalkyl, benzyl, alkoxy, haloalkoxy, alkenyloxy, and benzyloxy.

10 . A compound of claim 1 where Ar 1 is pyrazolyl substituted with 0-3 substituents selected from halo, cyano, alkyl, haloalkyl, benzyl, alkoxy, haloalkoxy, alkenyloxy, and benzyloxy.

11 . A composition useful for treating HIV infection comprising a therapeutic amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

12 . The composition of claim 11 further comprising a therapeutically effective amount at least one other agent used for treatment of AIDS or HIV infection selected from the group consisting of 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.

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

14 . The method of claim 13 further comprising administering a therapeutically effective amount of at least one other agent used for treatment of AIDS or HIV infection selected from the group consisting of 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.

Assignees

• Viiv Healthcare Uk No 5 Ltd

Inventors

• Connolly Timothy P
• Eastman Kyle J
• Naidu B Narasimhulu
• Peese Kevin

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

• A61P31/18

  for HIV · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title

• A61K45/06

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