Inhibitors of HIV replication

Patent metadata

Field	Value
Publication number	US-9399645-B2
Application number	US-201214366421-A
Country	US
Kind code	B2
Filing date	Dec 19, 2012
Priority date	Dec 20, 2011
Publication date	Jul 26, 2016
Grant date	Jul 26, 2016

Abstract

Compounds of formula (I) and pharmaceutical compositions thereof: wherein A 1 A 2 and A 3 are each independently selected from the group consisting of N and CR 3 , wherein R 1 is an optionally substituted heterocyclyl or an optionally substituted —(C 1-6 )alkyl-heterocyclyl, R 2 is an optionally substituted aryl or an optionally subsisted heteroaryl, R 4 is an optionally substituted aryl, an optionally substituted heterocyclyl or an optionally substituted heteroaryl, useful as an inhibitor of HIV replication.

First claim

The invention claimed is:

1. A compound of formula (I) or a racemate, enantiomer, diastereomer or tautomer thereof:

wherein
R 1 is

optionally substituted with 1 to 2 substituents each independently selected from —(C 1-3 )alkyl;
R 2 is a 5- or 6-membered heteroaryl selected from the group consisting of

 wherein each said heteroaryl is optionally substituted with 1 or 2 substituents independently selected from the group consisting of —(C 1-3 )alkyl, halo, —(C 1-3 )haloalkyl, —N(R 21 )(R 22 ) and —O(C 1-3 )alkyl;
R 21 is H or —(C 1-6 )alkyl optionally substituted 1 to 3 times with halo;
R 22 is H, —(C 2-6 )alkenyl or —(C 3-7 )cycloalkyl, wherein each said alkyl, alkenyl and cycloalkyl is optionally substituted 1 to 3 times with halo;

A 1 , A 2 and A 3 are each independently selected from the group consisting of N and CR 3 , wherein R 3 is independently in each instance selected from the group consisting of H, halo —CN, —N(R 21 )(R 22 ), —O(C 1-6 )alkyl, —(C 3-7 )cycloalkyl and —(C 1-6 )alkyl, wherein each said alkyl and cycloalkyl is optionally substituted with 1 to 3 substituents each independently selected from the group consisting of —O(C 1-6 )alkyl and halo;
R 4 is a 5- or 6-membered heteroaryl selected from the group consisting of

 wherein said heteroaryl is optionally substituted with 1 to 2 substituents each independently selected from the group consisting of halo and —(C 1-3 )alkyl optionally substituted one time with OH or —O(C 1-3 )alkyl;
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein A 1 , A 2 and A 3 are each independently selected from CR 3 .

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein one of A 1 , A 2 and A 3 is N and the remaining two of A 1 , A 2 and A 3 are each independently selected from CR 3 .

4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is independently in each instance selected from the group consisting of H, halo, —CN, —O(C 1-6 )alkyl and —(C 1-6 )alkyl optionally substituted with —O(C 1-6 )alkyl.

5. The compound according to claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 3 is independently in each instance selected from the group consisting of H, F, —CN, and —CH 3 .

6. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof; and one or more pharmaceutically acceptable carriers.

7. The pharmaceutical composition according to claim 6 , further comprising at least one other antiviral agent.

8. A method of treating an HIV infection in a human being having or at risk of having the infection comprising administering to the patient a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

Assignees

• Boehringer Ingelheim Int

Inventors

• Sturino Claudio
• Beaulieu Pierre
• Deroy Patrick
• Duplessis Martin
• James Clint
• Lacoste Jean-Eric
• Minville Joannie
• Morency Louis
• Morin Sébastien
• Simoneau Bruno
• Tremblay Martin

Classifications

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K31/519

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

• C07D491/048

  the oxygen-containing ring being five-membered · CPC title

• A61K45/06

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