US 8,796,283 B2 · Indole and azaindole modulators of the alpha 7 nachr

Abstract

This invention relates to modulation of the α7 nicotinic acetylcholine receptor (nAChR) by a compound of formula (I): or a pharmaceutically acceptable salt thereof.

Claims11

Dependent claims

A compound of formula (I):

wherein:
R1 is independently selected from the group consisting of H, C1-6alkyl, haloC1-6alkyl and halo;
R2 is independently selected from the group consisting of C1-6alkyl, haloC1-6alkyl, halo, acetyl, cyano, CH2CN and cyclopropyl;
and
X is CH or N;
or a pharmaceutically acceptable salt thereof.

3 more elements

A compound which is:

6-(trifluoromethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(1-methylethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl-4-pyrimidinamine;
6-({[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}amino)-4-pyrimidinecarbonitrile;
6-(1,1-dimethylethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-ethyl-N-([2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
[6-({[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}amino)-4-pyrimidinyl]acetonitrile;
1-[6-({[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}) amino)-4-pyrimidinyl]ethanone;
6-(1,1-difluoroethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(1-fluoroethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(difluoromethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(fluoromethyl)-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(trifluoromethyl)-N-{[2-(trifluoromethyl)-1H-indol-5-yl]methyl}-4-pyrimidinanmine;
6-chloro-N-{[2-(trifluoromethyl)-1H-indol-5-yl]methyl}-4-pyrimidinamine;
6-cyclopropyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl)}4-pyrimidinamine;
6-(1-fluoro-1-methylethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-ethyl-5-fluoro-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-chloro-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
or
6-ethyl-N-{[2-(trifluoromethyl)-1H-indol-5-yl]methyl}-4-pyrimidinamine;
6-ethyl-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(1-fluoroethyl)-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(1,1-difluoroethyl)-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl)}-4-pyrimidinamine;
5-methyl-6-(trifluoromethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(difluoromethyl)-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(fluoromethyl)-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
or
6-cyclopropyl-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
or a pharmaceutically acceptable salt thereof.

25 more elements

Dependencies are inferred from the claim text.

Facts

Application

13/501,418Filed 14 Oct 2010 · us provisional application

Priority

GB 1012686.028 Jul 2010

Published

US 2012/0283273 A18 Nov 2012

Granted

5 Aug 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61P 25/00
Drugs for disorders of the nervous system
A61P 25/04
Drugs for disorders of the nervous system: centrally acting analgesics, e.g. opioids

Abstract

This invention relates to modulation of the α7 nicotinic acetylcholine receptor (nAChR) by a compound of formula (I): or a pharmaceutically acceptable salt thereof.

Claims11

Dependent claims

A compound of formula (I):

wherein:
R1 is independently selected from the group consisting of H, C1-6alkyl, haloC1-6alkyl and halo;
R2 is independently selected from the group consisting of C1-6alkyl, haloC1-6alkyl, halo, acetyl, cyano, CH2CN and cyclopropyl;
and
X is CH or N;
or a pharmaceutically acceptable salt thereof.

3 more elements

A compound which is:

6-(trifluoromethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(1-methylethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl-4-pyrimidinamine;
6-({[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}amino)-4-pyrimidinecarbonitrile;
6-(1,1-dimethylethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-ethyl-N-([2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
[6-({[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}amino)-4-pyrimidinyl]acetonitrile;
1-[6-({[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}) amino)-4-pyrimidinyl]ethanone;
6-(1,1-difluoroethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(1-fluoroethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(difluoromethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(fluoromethyl)-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(trifluoromethyl)-N-{[2-(trifluoromethyl)-1H-indol-5-yl]methyl}-4-pyrimidinanmine;
6-chloro-N-{[2-(trifluoromethyl)-1H-indol-5-yl]methyl}-4-pyrimidinamine;
6-cyclopropyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl)}4-pyrimidinamine;
6-(1-fluoro-1-methylethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-ethyl-5-fluoro-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-chloro-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
or
6-ethyl-N-{[2-(trifluoromethyl)-1H-indol-5-yl]methyl}-4-pyrimidinamine;
6-ethyl-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(1-fluoroethyl)-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(1,1-difluoroethyl)-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl)}-4-pyrimidinamine;
5-methyl-6-(trifluoromethyl)-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(difluoromethyl)-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
6-(fluoromethyl)-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
or
6-cyclopropyl-5-methyl-N-{[2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}-4-pyrimidinamine;
or a pharmaceutically acceptable salt thereof.

25 more elements

Dependencies are inferred from the claim text.

Facts

Application

13/501,418Filed 14 Oct 2010 · us provisional application

Priority

GB 1012686.028 Jul 2010

Published

US 2012/0283273 A18 Nov 2012

Granted

5 Aug 2014

Term ends

Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07D 471/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61P 25/00
Drugs for disorders of the nervous system
A61P 25/04
Drugs for disorders of the nervous system: centrally acting analgesics, e.g. opioids

Indole and azaindole modulators of the alpha 7 nachr

Life of this patent

Abstract

Claims11

Indole and azaindole modulators of the alpha 7 nachr

Life of this patent

Abstract

Claims11