5-HT3 receptor antagonists

Patent metadata

Field	Value
Publication number	US-9670229-B2
Application number	US-201615150013-A
Country	US
Kind code	B2
Filing date	May 9, 2016
Priority date	Jul 17, 2012
Publication date	Jun 6, 2017
Grant date	Jun 6, 2017

Abstract

The present invention provides 5-HT3 receptor antagonists of Formula (I):

which are useful for the treatment of diseases treatable by inhibition of 5-HT3 receptor such as emesis, pain, drug addiction, neurodegenerative and psychiatric disorders, and GI disorders. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

First claim

What is claimed is:

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof or N-oxide thereof, wherein:
Z is O or NR a , wherein is hydrogen or C 1-6 alkyl;
R 1 is a ring of the formula (a)-(h) below:

R 2 is hydrogen, C 1-6 alkyl, or C 1-6 haloalkyl;
each R 3 is independently hydrogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, or halo, and can be present on any carbon atom in the rings;
R 4 is pyridinyl or pyrazolyl, each optionally substituted with one or two substituents independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 alkoxy, cyano, and halo;
X 1 , X 2 , X 3 , and X 4 are each CR 5 ;
each R 5 is independently hydrogen, C 1-6 alkyl, halo, hydroxy, or cyano, provided that at least one of R 5 is hydrogen; and
X 5 is N.

2. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 is a ring of formula (a) or (d).

3. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 is a ring of formula (e), (f), or (g).

4. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 is a ring of formula (e).

5. The compound or pharmaceutically acceptable salt of claim 1 , wherein each R 3 is hydrogen.

6. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 2 is hydrogen and each R 3 is hydrogen.

7. The compound or pharmaceutically acceptable salt of claim 1 , wherein each R 3 is independently hydrogen or methyl and R 2 is C 1-6 alkyl.

8. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 2 is methyl and each R 3 is hydrogen.

9. The compound or pharmaceutically acceptable salt of claim 1 , wherein each R 5 is hydrogen.

10. The compound of claim 1 which is
N-((1R,5S,7S)-9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-1-(pyridin-2-yl)-1H-indazole-3-carboxamide or a pharmaceutically acceptable salt of each above mentioned compound.

11. A pharmaceutical composition comprising a compound as defined in claim 1 and a pharmaceutically acceptable excipient.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Hitchcock Stephen
• Monenschein Holger
• Reichard Holly
• Sun Huikai
• Kikuchi Shota
• Macklin Todd
• Hopkins Maria

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

• A61P39/02

  Antidotes · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P43/00

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

• A61P39/00

  General protective or antinoxious agents · CPC title