Substituted imidazo[1,5-a]pyrazines as CGRP receptor antagonists

Patent metadata

Field	Value
Publication number	US-9695176-B2
Application number	US-201314433693-A
Country	US
Kind code	B2
Filing date	Oct 14, 2013
Priority date	Oct 18, 2012
Publication date	Jul 4, 2017
Grant date	Jul 4, 2017

Abstract

The disclosure generally relates to the novel compounds of formula I, including pharmaceutically acceptable salts, which are CGRP receptor antagonists. The disclosure also relates to pharmaceutical compositions and methods for using the compounds in the treatment of CGRP related disorders including migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD).

First claim

The invention claimed is:

1. A compound of formula I

where:
R 1 is hydrogen, alkyl, cycloalkyl, or (Ar 2 )alkyl;
R 2 is piperidinyl, substituted with one substituent selected from the group consisting of

R 3 is hydrogen, halo, cyano, alkyl, haloalkyl, alkoxy, or haloalkoxy;
R 4 is hydrogen, halo, cyano, alkyl, haloalkyl, alkoxy, or haloalkoxy;
Ar 1 is indazolyl, optionally substituted with one substituent selected from the group consisting of halo, alkyl, and haloalkyl;
Ar 2 is phenyl, optionally substituted with one, two or three substituents selected from the group consisting of halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; and
X is O, CH 2 , or NH;
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , where R 1 is hydrogen, ethyl, cyclohexyl, or benzyl.

3. The compound of claim 1 , where R 2 is piperidinyl, 4-substituted with one substituent selected from the group consisting of

4. The compound of claim 1 , where Ar 1 is indazolyl, substituted with one alkyl substituent.

5. The compound of claim 1 , where Ar 2 is phenyl.

6. The compound of claim 1 , where X is O.

7. The compound of claim 1 , where:
R 1 is hydrogen, alkyl, cycloalkyl, or (Ar 2 )alkyl;
R 2 is piperidinyl, substituted with one substituent selected from the group consisting of

R 3 is hydrogen;
R 4 is hydrogen;
Ar 1 is indazolyl, substituted with one alkyl substituent;
Ar 2 is phenyl; and
X is O;

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , where:
R 1 is hydrogen, ethyl, cyclohexyl, or benzyl;

R 2 is piperidinyl, substituted with one substituent;
R 3 is hydrogen;
R 4 is hydrogen;
Ar 1 is indazolyl, substituted with one methyl substituent;
Ar 2 is phenyl; and
X is O;

or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignees

• Bristol Myers Squibb Co

Inventors

• Degnan Andrew P

Classifications

• A61P25/06

  Antimigraine agents · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61P11/06

  Antiasthmatics · CPC title