SGC stimulators

Patent metadata

Field	Value
Publication number	US-9309235-B2
Application number	US-201314428844-A
Country	US
Kind code	B2
Filing date	Sep 18, 2013
Priority date	Sep 18, 2012
Publication date	Apr 12, 2016
Grant date	Apr 12, 2016

Abstract

Compounds of Formula I are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed.

First claim

The invention claimed is:

1. A compound according to Formula I, or a pharmaceutically acceptable salt thereof,

wherein:
ring B is a 5-membered heteroaryl ring selected from furan or thiophene;
n is an integer selected from 0 to 3;
each J B is independently selected from halogen, —CN, a C 1-6 aliphatic, —OR B or a C 3-8 cycloaliphatic group; wherein each said C 1-6 aliphatic and each said C 3-8 cycloaliphatic group is optionally and independently substituted with up to 3 instances of R 3 ;
each R B is independently selected from hydrogen, a C 1-6 aliphatic or a C 3-8 cycloaliphatic ring; wherein each said C 1-6 aliphatic and each said C 3-8 cycloaliphatic ring is optionally and independently substituted with up to 3 instances of R 3a ;
each R 3 is independently selected from halogen, —CN, C 1-4 alkyl, C 1-4 haloalkyl, —O(C 1-4 alkyl) or —O(C 1-4 haloalkyl);
each R 3a is independently selected from halogen, —CN, C 1-4 alkyl, C 1-4 haloalkyl, —O(C 1-4 alkyl) or —O(C 1-4 haloalkyl);
X is selected from N, C-J D or C—H;
o is an integer selected from 0 to 3;
each J D is independently selected from halogen, —NO 2 , —OR D , —SR D , —C(O)R D , —C(O)OR D , —C(O)N(R D ) 2 , —CN, —N(R D ) 2 , —N(R d )C(O)R D , —N(R d )C(O)OR D , —SO 2 R D , —SO 2 N(R D ) 2 , —N(R d )SO 2 R D , a C 1-6 aliphatic, —(C 1-6 aliphatic)-R D , a C 3-8 cycloaliphatic ring, a 6 to 10-membered aryl ring, a 4 to 8-membered heterocyclic ring or a 5 to 10-membered heteroaryl ring; wherein each said 4 to 8-membered heterocylic ring and each said 5 to 10-membered heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C 1-6 aliphatic, each said C 3-8 cycloaliphatic ring, each said 6 to 10-membered aryl ring, each said 4 to 8-membered heterocyclic ring and each said 5 to 10-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of R 5 ;
each R D is independently selected from hydrogen, a C 1-6 aliphatic, —(C 1-6 aliphatic)-R f , a C 3-8 cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or a 5 to 6-membered heteroaryl ring; wherein each said 4 to 8-membered heterocylic ring and each said 5 to 6-membered heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C 1-6 aliphatic, each said C 3-8 cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted with up to 3 instances of R 5a ;
each R d is independently selected from hydrogen, a C 1-6 aliphatic, —(C 1-6 aliphatic)-R f , a C 3-8 cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or a 5 to 6-membered heteroaryl ring; wherein each said heterocylic ring and each said heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C 1-6 aliphatic, each said C 3-8 cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R 5b ;
each R f is independently selected from a C 3-8 cycloaliphatic ring, a 4 to 8-membered heterocyclic ring, phenyl or a 5 to 6-membered heteroaryl ring; wherein each said heterocylic ring and each said heteroaryl ring contains between 1 and 3 heteroatoms independently selected from O, N or S; and wherein each said C 1-6 aliphatic, each said C 3-8 cycloaliphatic ring, each said 4 to 8-membered heterocyclic ring, each said phenyl and each said 5 to 6-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R 5c ;
when J D is —C(O)N(R D ) 2 , —N(R D ) 2 or —SO 2 N(R D ) 2 , the two instances of R D together with the nitrogen atom attached to the R D , alternatively form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R 5 ; or
when J D is —N(R d )C(O)R D , the R D group together with the carbon atom attached to the R D group, with the nitrogen atom attached to the R d group and with the R d group alternatively form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R 5 ;
when J D is —N(R d )C(O)OR D , the R D group together with the oxygen atom attached to the R D group, with the carbon atom of the —C(O)— portion of the —N(R d )C(O)OR D group, with the nitrogen atom attached to the R d group, and with the R d group alternatively form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R 5 ;
when J D is —N(R d )SO 2 R D , the R D group together with the oxygen atom attached to the R D group, with the sulfur atom attached to said oxygen atom in the —SO 2 R D portion of the —N(R d )SO 2 R D group, with the nitrogen atom attached to the R d group, and with the R d group alternatively form a 4 to 8-membered heterocyclic ring or a 5-membered heteroaryl ring; wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring optionally contains up to 2 additional heteroatoms independently selected from N, O or S, and wherein each said 4 to 8-membered heterocyclic ring and each said 5-membered heteroaryl ring is optionally and independently substituted by up to 3 instances of R 5 ;
each R 5 is independently selected from halogen, —CN, —NO 2 , C 1-4 alkyl, a C 7-12 aralkyl, C 3-8 cycloalkyl ring, C 1-4 haloalkyl, C 1-4 cyanoalkyl, —OR 6 , —SR 6 , —OCOR 6 , —COR 6 , —C(O)OR 6 , —C(O)N(R 6 ) 2 , —N(R 6 )C(O)R 6 , —N(R 6 ) 2 , —SO 2 R 6 , —SO 2 N(R 6 ) 2 , —N(R 6 )SO 2 R 6 , phenyl or an oxo group; wherein each said phenyl group is optionally and independently substituted with up to 3 instances of halogen, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —NO 2 , —CN, C 1-4 alkyl, C 1-4 haloalkyl, —O(C 1-4 alkyl) or —O(C 1-4 haloalkyl); and wherein each said C 7-12 aralkyl and each said cycloalkyl group is optionally and independently substituted with up to 3 instances of halogen;
each R 5a is independently selected from halogen, —CN, —NO 2 , C 1-4 alkyl, a C 7-12 aralkyl, C 3-8 cycloalkyl ring, C 1-4 haloalkyl, C 1-4 cyanoalkyl, —OR 6 , —SR 6 , —OCOR 6 , —COR 6 , —C(O)OR 6 , —C(O)N(R 6 ) 2 , —N(R 6 )C(O)R 6 , —N(R 6 ) 2 , —SO 2 R 6 , —SO 2 N(R 6 ) 2 , —N(R 6 )SO 2 R 6 , phenyl or an oxo group; wherein each said phenyl group is optionally and independently substituted with up to 3 instances of halogen, —OH, —NH 2 , —NH(C 1-4 alkyl), —N(C 1-4 alkyl) 2 , —NO 2 , —CN, C 1-4 alkyl, C 1-4 haloalkyl, —O(C 1-4 alkyl) or —O(C 1-4 haloalkyl); and where

Assignees

• Ironwood Pharmaceuticals Inc

Inventors

• Im G-Yoon Jamie
• Iyengar Rajesh
• Moore Joel
• Fretzen Angelika

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• C07D413/14 Primary

  containing three or more hetero rings · CPC title

• A61P13/00

  Drugs for disorders of the urinary system · CPC title

• A61K31/513 Primary

  having oxo groups directly attached to the heterocyclic ring, e.g. cytosine · CPC title

• C07D409/14

  containing three or more hetero rings · CPC title