IDO inhibitors

Patent metadata

Field	Value
Publication number	US-9895330-B2
Application number	US-201414903091-A
Country	US
Kind code	B2
Filing date	Jul 10, 2014
Priority date	Jul 11, 2013
Publication date	Feb 20, 2018
Grant date	Feb 20, 2018

Abstract

There are disclosed compounds of Formula (I) that modulate or inhibit the enzymatic activity of indoleamine 2,3-di-oxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or autoimmune diseases utilizing the compounds of the invention.

First claim

What is claimed is:

1. A compound of formula (II)

wherein:

 is phenyl optionally substituted with halo,
R 1 is COOH or tetrazol-5-yl;
R 2 and R 3 are independently H;
R 4 and R 5 are independently H or halo;
R 6 is H;
R 7 and R 8 are independently H, C 1 -C 6 alkyl optionally substituted with halogen, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkenyl, aryl, C 1 -C 6 alkoxyl optionally substituted with C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl optionally substituted with C 1 -C 6 alkyl, and aryl C 1 -C 6 alkyl,
provided that only one of R 7 and R 8 is H,
or R 7 and R 8 are taken together with the nitrogen to which they are attached to form

R 9 is

 or —COOR 12 ;
R 10 is aryl optionally substituted with C 1 -C 6 alkyl, CN, haloalkyl, or halogen, C 1 -C 6 alkyl, 5- to 7-membered monocyclic heteroaryl optionally substituted with C 1 -C 6 alkyl, halo and CN;
R 11 is H or OH;
R 12 is aryl optionally substituted with C 1 -C 6 alkyl, nitro, halogen, alkoxyl, aryloxyl or benzodioxolyl;
and/or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

2. The compound as defined in claim 1 wherein

is phenyl, and/or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

3. The compound as defined in claim 1 wherein:
R 1 is tetrazol-5-yl or COOH;
R 2 is H and
R 3 is H,
and/or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

4. The compound as defined in claim 1 wherein:
R 7 and R 8 are independently optionally substituted C 1 -C 6 alkoxyl, or optionally substituted C 3 -C 8 cycloalkyl;
or R 7 and R 8 are taken together with the nitrogen to which they are attached to form

and
R 9 is

or —COOR 12 ;
R 11 is H; and
R 12 is naphthyl, nitroaryl, phenyl, C 1 -C 6 alkylphenyl, C 1 -C 6 alkoxyphenyl,

C 1 -C 6 alkoxy(halo)phenyl, halophenyl, or phenyl-C 1 -C 6 -alkoxyphenyl;
and/or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

5. A compound selected from the group consisting of 4′-(Diisobutylamino)-5-fluoro-3′-(2-p-tolylacetamido)biphenyl-2-carboxylic acid; N-(4-(Diisobutylamino)-2′-(1H-tetrazol-5-yl)biphenyl-3-yl)-2-p-tolylacetamide; N,N-(4-(Benzyl(isobutyl)amino)-2′-(1H-tetrazol-5-yl)biphenyl-3-yl)-2-(2-(trifluoromethyl)phenyl)acetamide; 4′-(diisobutylamino)-3′-(2-p-tolylacetamido)biphenyl-2-carboxylic acid; 4′-(cyclohexyl(isobutyl)amino)-3′-(2-(2-fluorophenyl)acetamido)biphenyl-2-carboxylic acid; 4′-(cyclohexyl(isobutyl)amino)-5-fluoro-3′-(2-(2-fluorophenyl)acetamido)biphenyl-2-carboxylic acid; and N-(4-(cyclohexyl(isobutyl)amino)-2′-(1H-tetrazol-5-yl)biphenyl-3-yl)-2-(2-(trifluoromethyl) phenyl)acetamide and/or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

6. The compound that is 4′-(Diisobutylamino)-5-fluoro-3′-(2-p -tolylacetamido)biphenyl-2-carboxylic acid; N-(4-(Diisobutylamino)-2′-(1H-tetrazol-5-yl)biphenyl-3-yl)-2-p -tolylacetamide or a pharmaceutically acceptable salt thereof.

7. The compound that is N-(4-(Diisobutylamino)-2′-(1H-tetrazol-5-yl)biphenyl-3-yl)-2-p-tolylacetamide or a pharmaceutically acceptable salt thereof.

8. The compound that is N,N-(4-(Benzyl(isobutyl)amino)-2′-(1H-tetrazol-5-yl)biphenyl-3-yl)-2-(2-(trifluoromethyl)phenyl)acetamide or a pharmaceutically acceptable salt thereof.

9. The compound that is 4′-(cyclohexyl(isobutyl)amino)-3′-(2-(2-fluorophenyl)acetamido)biphenyl-2-carboxylic acid or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising one or more compounds according to claim 1 and a pharmaceutically acceptable carrier or diluent.

Assignees

• Bristol Myers Squibb Co

Inventors

• Markwalder Jay A
• Balog James Aaron
• Huang Audris
• Seitz Steven P

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P31/12

  Antivirals · CPC title