Ido inhibitors

Patent metadata

Field	Value
Publication number	US-2016200674-A1
Application number	US-201414914184-A
Country	US
Kind code	A1
Filing date	Aug 26, 2014
Priority date	Aug 27, 2013
Publication date	Jul 14, 2016
Grant date	—

Abstract

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (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 (I)

wherein:
W is CR 4 or N,
V is CR 5 or N, and
Y is CR 6 or N;

is optionally substituted aryl or optionally substituted 5- to 7-membered monocyclic heteroaryl;
R 1 is COOH, optionally substituted heterocyclyl, —NHSO 2 R 20 ,

 -CONHSO 2 R 21 , —CONHCOOR 22 or —SO 2 NHCOR 23 ;
R 2 and R 3 are independently H, halogen, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy or optionally substituted N(C 1 -C 6 alkyl) 2 ;
R 4 , R 5 and R 6 are independently H, halogen, CN, OH, optionally substituted C 1 -C 6 alkyl or optionally substituted C 1 -C 6 alkoxy;
R 7 and R 8 are independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted aryl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted di-deutero-C 1 -C 10 -alkyl, optionally substituted C 2 -C 10 alkynyl, optionally substituted 5- to 7-membered monocyclic heteroaryl, optionally substituted 8- to 10-membered bicyclic heteroaryl, optionally substituted aryl C 1 -C 6 alkyl, arylsulfonyl, optionally substituted C 2 -C 6 alkenyl, or optionally substituted C 5 -C 8 cycloalkenyl,
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 an optionally substituted 4- to 10-membered monocyclic or bicyclic heterocyclic ring, or an optionally substituted 5- to 7-membered monocyclic heteroaryl ring;
R 9 is optionally substituted aryl; optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 1 -C 6 alkyl, optionally substituted 5- to 7-membered monocyclic heterocyclo, optionally substituted 7- to 10-membered bicyclic heterocyclo, optionally substituted 5- to 7-membered monocyclic heteroaryl, optionally substituted 8- to 10-membered bicyclic heteroaryl, optionally substituted C 1 -C 6 alkanoyloxy 5- to 7-membered monocyclic heteroaryl, R 24 CO—, optionally substituted C 1 -C 6 alkoxy, optionally substituted aryloxy, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, or optionally substituted C5-C8 cycloalkenyl;
R 20 is optionally substituted C 1 -C 6 alkyl, CH 2 CF 3 , CF 3 or CF 2 CF 3 ;
R 21 is optionally substituted C 1 -C 6 alkyl or optionally substituted C 3 -C 8 cycloalkyl;
R 22 is optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 2 -C 6 alkenyl, or optionally substituted C 2 -C 6 alkynyl;
R 23 is optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 2 -C 6 alkenyl, or optionally substituted C 2 -C 6 alkynyl;
R 24 is optionally substituted aryl-C 1 -C 6 -alkyl, optionally substituted C 1 -C 6 alkylaryl, aryl-C 1 -C 6 -alkyl(hydroxy), or optionally substituted C 1 -C 6 alkyl;
and/or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

2 . The compound as defined in claim 1 wherein:
W is CR 4 ;
V is CR 5 ;
Y is CR 6 or N;
R 4 is H or halo;
R 5 is H or halo; and
R 6 is H or halo;
and/or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

3 . The compound as defined in claim 1 wherein

is phenyl or a 5- to 6-membered monocyclic heteroaryl.

4 . The compound as defined in claim 3 wherein

is:

5 . The compound as defined in claim 1 wherein:
R 1 is COOH, optionally substituted heterocyclyl, —NHSO 2 R 20 ,

 —CONHSO 2 R 21 or —CONHCOOR 22 ;
R 2 is H, halogen, optionally substituted C 1 -C 6 alkyl or optionally substituted C 1 -C 6 alkoxy; and
R 3 is H or C 1 -C 6 alkyl.

6 . The compound as defined in claim 5 wherein:
R 1 is COOH, optionally substituted heterocyclyl, —NHSO 2 CH 3 ,

 or —CONHSO 2 R 21 ;
where R 21 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl or CF 3 ;
R 2 is H, CH 3 , C 2 H 5 , CH 3 O, CF 3 O, F, or Cl; and
R 3 is H, CH 3 , or C 2 H 5 ;
and/or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

7 . The compound as defined in claim 1 wherein:
R 7 and R 8 are independently optionally substituted C 1 -C 6 alkyl, optionally substituted aryl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted di-deutero-C 1 -C 6 -alkyl, optionally substituted C 1 -C 6 -alkylphenyl-C 1 -C 6 -alkyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 3 -C 8 -cycloalkyl-C 1 -C 6 -alkyl, optionally substituted C 1 -C 6 -alkoxy-C 1 -C 6 -alkyl, optionally substituted 5- to 6-membered monocyclic heteroaryl, optionally substituted 7- to 10-membered bicyclic heteroaryl, optionally substituted aryl C 1 -C 6 alkyl, phenylsulfonyl, optionally substituted C 2 -C 6 alkenyl, or 5- to 6-membered monocyclic heteroaryl-C 1 -C 6 -alkyl,
or R 7 and R 8 are taken together with the nitrogen to which they are attached to form
(a) a 7- to 10-membered bicyclic heterocyclic ring which is optionally substituted with a phenyl-C 1 -C 6 -alkyl group, or
(b) a 5- to 7-membered monocyclic heterocyclic ring which is optionally substituted with 1 or 2 C 1 -C 6 alkyl groups, phenyl, a C 1 -C 6 -alkyl-substituted 5- to 7-membered monocyclic heteroaryl, and/or 1 or 2 halo groups; or
(c) a 5- to 7-membered monocyclic heteroaryl which is optionally substituted with a C 1 -C 6 alkyl;
R 9 is optionally substituted aryl; optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 1 -C 6 alkylaryl, optionally substituted C 1 -C 6 alkoxyaryl, optionally substituted C 3 -C 8 cycloalkyl C 1 -C 6 alkyl, optionally substituted 5- to 7-membered monocyclic heterocyclo, optionally substituted 7- to 10-membered bicyclic heterocyclo, optionally substituted 5- to 6-membered monocyclic heteroaryl, optionally substituted 8- to 10-membered bicyclic heteroaryl, optionally substituted C 1 -C 6 alkanoyloxy 5- to 7-membered monocyclic heteroaryl, optionally substituted aryloxy, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, or optionally substituted C5-C8 cycloalkenyl, C 2 -C 6 alkynylaryl, C 2 -C 6 alkynyloxyaryl, 5- to 6-membered heteroarylaryl, 5- or 6-membered heterocycloaryl, C 3 -C 8 cycloalkylaryl or C 1 -C 6 alkanoyl.

8 . A compound of Formula (II)

wherein:
Y is CR 6 or N;

is phenyl sub

Assignees

• Bristol Myers Squibb Co

Inventors

• Markwalder Jay A
• Seitz Steven P
• Balog James Aaron
• Huang Audris
• Mandal Sunil Kumar
• Srivastava Shefali
• Williams David K
• Chen Libing

Classifications

• A61P43/00

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

• A61P37/06

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

• A61P37/02

  Immunomodulators · CPC title

• C07B59/002

  Heterocyclic compounds · CPC title

• C07D411/12

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