6-(5-hydroxy-1H-pyrazol-1-YL)nicotinamide inhibitors of PHD

Patent metadata

Field	Value
Publication number	US-9944626-B2
Application number	US-201715620620-A
Country	US
Kind code	B2
Filing date	Jun 12, 2017
Priority date	Mar 29, 2013
Publication date	Apr 17, 2018
Grant date	Apr 17, 2018

Abstract

The present invention provides compounds of the formula:

which are useful as inhibitors of PHD, pharmaceutical compositions thereof, methods for treatment of conditions associated with HIF, processes for making the compounds and intermediates thereof.

First claim

What is claimed is:

1. A compound of formula 5,

or a pharmaceutically acceptable salt thereof, wherein:
R 3 , each time taken, is independently selected from the group consisting of hydrogen, hydroxyl, amino, C 1-8 alkylamino, cyano, halo, C 1-6 alkyl, and C 1-4 alkoxy;
R 4 is selected from the group consisting of hydrogen, cyano, halo, methyl, ethyl, methoxy, and trifluoromethyl;
R 5 is selected from the group consisting of

R 6 , each time taken, is independently selected from the group consisting of hydrogen, cyano, halo, C 3-8 cycloalkyl, C 1-6 alkyl, C 1-4 alkoxy, and trifluoromethyl;
R 7 is selected from the group consisting of cyano and cyanomethyl; and
R 8 , each time taken, is independently selected from the group consisting of hydrogen, cyano, halo, C 1-4 alkyl, C 1-4 alkoxy, and trifluoromethyl.

2. The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 5 is

3. The compound or pharmaceutically acceptable salt according to claim 1 , wherein R 6 is C 1-6 alkyl.

4. The compound or pharmaceutically acceptable salt according to claim 1 , wherein each R 8 is hydrogen.

5. The compound or pharmaceutically acceptable salt according to claim 1 , wherein each R 3 is hydrogen and R 4 is hydrogen.

6. The compound according to claim 1 , which is selected from the group consisting of:
4-(5-hydroxy-1-(5-(morpholine-4-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)benzonitrile;
2-fluoro-4-(5-hydroxy-1-(5-(morpholine-4-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-methylbenzonitrile;
2-fluoro-4-(5-hydroxy-1-(5-(morpholine-4-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-5-methylbenzonitrile; and
a pharmaceutically acceptable salt of any one of the above-mentioned compounds.

7. A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt as defined in claim 1 ; and a pharmaceutically acceptable excipient.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Brown Jason W
• Davis Melinda
• Ivetac Anthony
• Jones Benjamin
• Kiryanov Andre A
• Kuehler Jon
• Lanier Marion
• Miura Joanne
• Murphy Sean
• Wang Xiaolun

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

• A61P43/00

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P7/06

  Antianaemics · CPC title

• A61P13/12

  of the kidneys · CPC title