Fused heterocyclic compounds as selective BMP inhibitors

Patent metadata

Field	Value
Publication number	US-9738636-B2
Application number	US-201314432472-A
Country	US
Kind code	B2
Filing date	Mar 15, 2013
Priority date	Sep 28, 2012
Publication date	Aug 22, 2017
Grant date	Aug 22, 2017

Abstract

The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.

First claim

We claim:

1. A compound having a structure represented by the following formula (I):

wherein:
X, Y, and Z are independently N or CH;

each A 1 is independently O,S,CR 1 R 2 or NR 1 ;
R is selected from CF 3 , halogen, CN, alkyl, S(O) 0-2 , NR 1 R 2 , or S(O) 0-2 R 1 R 2 ;
M is substituted or unsubstituted and is selected from aryl or heteroaryl;
D is selected from a bond, O, CR 1 R 2 , NH, NR 1 , NR 1 R 2 , or S(O) 0-2 R 1 R 2 ;
E is absent or selected from H, CF 3 , halogen, CN, alkyl, aryl, heteroaryl, C 3 -C 12 cycloalkyl or C 3 -C 12 cycloheteroalkyl or —(CH 2 ) x —C 3 -C 12 cycloalkyl or —(CH 2 ) x —C 3 -C 12 cycloheteroalkyl;
R 1 is absent or selected from H, alkyl, aryl, or heteraryl; and
R 2 is selected from H, alkyl, aryl, heteraryl, COR 1 , or R 1 and R 2 can form a C 3 -C 12 cycloalkyl or C 3 -C 12 cycloheteroalkyl containing O, N or S; or a pharmaceutically acceptable salt thereof.

2. A compound of claim 1 , wherein X, Y and Z together help form:

3. A compound of claim 1 , wherein X, Y and Z together help form:

4. A compound of claim 1 , wherein M is optionally substituted with one or more R, and is selected from C 3 -C 12 cycloalkyl, C 3 -C 12 cycloalkenyl, aryl, heteroaryl, C 3 -C 12 heterocycloalkyl or C 3 -C 12 heterocycloalkenyl.

5. A compound of claim 4 , wherein M is optionally substituted phenyl or pyridine.

6. A compound of claim 1 , wherein M, D, and E together form:

7. A compound of claim 1 , wherein A is chosen from the following:

8. A compound of one of the following structures:

or a pharmaceutically acceptable salt thereof.

Assignees

• Univ Vanderbilt

Inventors

• Hopkins Corey R
• Hong Charles C
• Lindsley Craig W
• Engers Darren W

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P43/00

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

• A61P9/12

  Antihypertensives · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title