Cyanoisoquinoline compounds and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2016009653-A1
Application number	US-201514860560-A
Country	US
Kind code	A1
Filing date	Sep 21, 2015
Priority date	Jan 27, 2006
Publication date	Jan 14, 2016
Grant date	—

Abstract

The present invention relates to cyanoisoquinoline compounds suitable for use in treating hypoxia inducible factor-mediated and/or erythropoictin-associated conditions. The cyanoisoquinoline compounds of the invention have the following structure:

First claim

What is claimed is:

1 . A compound of formula II:

wherein
R 3 , R 32 , R 33 and R 34 are independently selected from the group consisting of hydrogen, substituted alkyl, aryl, aryloxy, and aryloxy optionally substituted with from 1 to 3 substituents independently selected from the group consisting of halo, alkoxy, and alkyl; and
R 35 is hydrogen or methyl;
or a pharmaceutically acceptable salt, tautomer, or stereoisomer thereof; or an ester or amide of the carboxylic acid moiety on the glycine- or alanine-based substituent of the cyanoisoquinoline ring.

2 . The compound of claim 1 , wherein R 31 , R 32 , R 33 and R 34 are independently selected from the group consisting of hydrogen, phenoxy and phenoxy substituted with halogen; and R 35 is hydrogen or methyl.

3 . The compound of claim 2 , wherein one of R 31 , R 32 , R 33 and R 34 is phenoxy substituted with halogen, the other three of R 31 , R 32 , R 33 and R 34 are hydrogen, and R 35 is hydrogen.

4 . The compound of claim 3 , wherein R 31 is phenoxy substituted with halogen, R 32 , R 33 and R 34 are hydrogen, and R 35 is hydrogen.

5 . The compound of claim 3 , wherein R 32 is phenoxy substituted with halogen, R 31 , R 33 and R 34 are hydrogen, and R 35 is hydrogen.

6 . The compound of claim 3 , wherein R 33 is phenoxy substituted with halogen, R 31 , R 32 and R 34 are hydrogen, and R 35 is hydrogen.

7 . The compound of claim 3 , wherein R 34 is phenoxy substituted with halogen, R 31 , R 32 and R 33 are hydrogen, and R 35 is hydrogen.

8 . A pharmaceutical composition comprising one or more compounds of claim 1 and a pharmaceutically acceptable excipient.

9 . The composition of claim 8 , further comprising at least one additional therapeutic agent.

10 . The composition of claim 9 , wherein the agent is selected from the group consisting of vitamin B12, folic acid, ferrous sulfate, human erythropoietin and an erythropoiesis stimulating protein (ESP).

Assignees

• Fibrogen Inc

Inventors

• Arend Michael
• Flippin Lee A
• Wu Min
• Turtle Eric D
• Ho Wen-Bin
• Deng Shaojiang

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

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P7/06

  Antianaemics · CPC title