2-phenyl or 2-hetaryl imidazol[1,2-a]pyridine derivatives

Patent metadata

Field	Value
Publication number	US-10138234-B2
Application number	US-201514925574-A
Country	US
Kind code	B2
Filing date	Oct 28, 2015
Priority date	Apr 29, 2013
Publication date	Nov 27, 2018
Grant date	Nov 27, 2018

Abstract

The invention relates to compounds of formula I:

and to pharmaceutically acceptable acid addition salts thereof, wherein R 1 -R 6 , R a , and R b have any of the values defined in the specification. The compounds are suitable as imaging tools.

First claim

We claim:

1. A compound selected from the group consisting of:
N-(2-fluoroethyl)-2-phenylimidazo[1,2-a]pyridin-7-amine,
N-(2-fluoroethyl)-N-methyl-2-phenylimidazo[1,2-a]pyridin-7-amine,
N,N-dimethyl-2-phenylimidazo[1,2-a]pyridin-7-amine,
N-methyl-2-phenylimidazo[1,2-a]pyridin-7-amine,
[2-(4-dimethylamino-phenyl)-imidazo[1,2-a]pyridin-7-yl]-dimethyl-amine,
(2-[4-(2-fluoro-ethoxy)-phenyl]-imidazo[1,2-a]pyridin-7-yl}-dimethyl-amine,
[2-(4-fluoromethoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-dimethyl-amine,
[2-(4-methoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-dimethyl-amine,
N-methyl-2-m-tolylimidazo[1,2-a]pyridin-7-amine,
N,N-dimethyl-(2-m-tolyl-imidazo[1,2-a]pyridin-7-yl)-amine,
N,N-dimethyl-(2-p-tolyl-imidazo[1,2-a]pyridin-7-yl)-amine,
N-methyl-(2-p-tolyl-imidazo[1,2-a]pyridin-7-yl)-amine,
N-(2-fluoroethyl)-N-methyl-(2-p-tolyl-imidazo[1,2-a]pyridin-7-yl)-amine,
2-(4-(dimethylamino)phenyl)-N-(2-fluoroethyl)-N-methylimidazo[1,2-a]pyridin-7-amine,
[2-(3-methoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-dimethyl-amine,
(2-fluoro-ethyl)-methyl-(2-m-tolyl-imidazo[1,2-a]pyridin-7-yl)-amine
[2-(3-methoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
[2-(4-fluoromethoxy-phenyl)-imidazo[1,2-a]pyri din-7-yl]-methyl-amine,
(2-fluoro-ethyl)-(2-p-tolyl-imidazo[1,2-a]pyridin-7-yl)-amine,
(2-fluoro-ethyl)-(2-m-tolyl-imidazo[1,2-a]pyridin-7-yl)-amine,
(2-fluoro-ethyl)-[2-(4-fluoromethoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-amine,
[2-(3,4-dimethyl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-dimethyl-amine,
[2-(3,4-dimethyl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
[ 3 H]-[2-(4-fluoromethoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
[ 3 H]—N-methyl-2-phenyl-imidazo[1,2-a]pyridin-7-amine,
[ 3 H]—N-(2-fluoroethyl)-2-phenyl-imidazo[1,2-a]pyridin-7-amine,
[ 3 H]—N-methyl-(2-p-tolyl-imidazo[1,2-a]pyridin-7-yl)-amine,
(2-fluoro-ethyl)-[2-(4-methoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
[2-(3,4-dimethoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
cyclopropyl-[2-(4-methoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-amine,
methyl-[2-(4-methyl sulfanyl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-amine,
[2-(3,4-dimethyl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-(2-fluoro-ethyl)-amine,
[2-(3,4-dimethoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-(2-fluoro-ethyl)-amine,
[2-(4-methoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
(2-fluoro-ethyl)-[2-(4-methoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-amine,
(2-fluoro-ethyl)-[2-(3-methoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-amine,
[2-(3-fluoromethoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-dimethyl-amine,
(2-fluoro-ethyl)-[2-(4-methyl sulfanyl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-amine,
cyclopropyl-[2-(4-fluoromethoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-amine,
2-methoxy-4-(7-methylamino-imidazo[1,2-a]pyridin-2-yl)-phenol,
3-(7-dimethylamino-imidazo[1,2-a]pyridin-2-yl)-phenol,
[4-[7-(methylamino)imidazo[1,2-a]pyridin-2-yl]phenyl]methanol,
[4-[7-(dimethylamino)imidazo[1,2-a]pyridin-2-yl]phenyl]methanol,
2-(3,5-dimethoxyphenyl)-N-methylimidazo[1,2-a]pyridin-7-amine,
N-[2-(4-ethoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
methyl-[2-(4-pyrrolidin-1-yl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-amine,
N-[2-(3-fluoro-4-methoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
N-[2-(4-diethylamino-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
N-[2-(4-ethyl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
2-[4-(methoxymethyl)phenyl]-N,N-dimethyl-imidazo[1,2-a]pyridin-7-amine,
methyl-[2-(4-morpholin-4-yl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-amine,
2-[4-(2-fluoroethoxymethyl)phenyl]-N,N-dimethyl-imidazo[1,2-a]pyridin-7-amine,
2-(3-methoxy-4-methylphenyl)-N-methylimidazo[1,2-a]pyridin-7-amine,
2-[4-(2-fluoroethoxy)phenyl]-N-methylimidazo[1,2-a]pyridin-7-amine,
2-(4-(benzyl(methyl)amino)phenyl)-N-methylimidazo[1,2-a]pyridin-7-amine,
N-[2-(4-difluoromethoxy-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
N-[2-(4-bromo-phenyl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
methyl-[2-(4-piperidin-1-yl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-amine,
2-(7-methylamino-imidazo[1,2-a]pyridin-2-yl)-phenol,
methyl 3-[7-(methylamino)imidazo[1,2-a]pyridin-2-yl]benzoate,
[3-[7-(methylamino)imidazo[1,2-a]pyridin-2-yl]phenyl]methanol,
N-cyclopropyl-2-[4-(2-fluoroethoxy)phenyl]imidazo[1,2-a]pyridin-7-amine,
7-(azetidin-1-yl)-2-[4-(3-fluoropropoxy)phenyl]imidazo[1,2-a]pyridine,
4-methyl-2-(7-methylamino-imidazo[1,2-a]pyridin-2-yl)-phenol,
2-[3-(methoxymethyl)phenyl]-N-methyl-imidazo[1,2-a]pyridine-7-amine,
2-(4-(2-fluoroethylamino)phenyl)-N-methylimidazo[1,2-a]pyridin-7-amine,
N-(3-fluoropropyl)-2-(4-methoxyphenyl)imidazo[1,2-a]pyridin-7-amine,
2-(3-(fluoromethoxy)phenyl)-N-methylimidazo[1,2-a]pyridin-7-amine,
2-(2-(4-methoxyphenyl)imidazo[1,2-a]pyridin-7-ylamino)propan-1-ol,
N-(2-fluoroethyl)-2-(3-methoxy-4-methylphenyl)imidazo[1,2-a]pyridin-7-amine,
N-methyl-2-(3-(methylthio)phenyl)imidazo[1,2-a]pyridin-7-amine,
2-(3-(2-fluoroethoxy)phenyl)-N-methylimidazo[1,2-a]pyridin-7-amine,
2-(3-(3-fluoropropoxy)phenyl)-N-methylimidazo[1,2-a]pyridin-7-amine,
2-(4-(4-fluoropiperidin-1-yl)phenyl)-N-methylimidazo[1,2-a]pyridin-7-amine,
4-(7-(2-fluoroethylamino)imidazo[1,2-a]pyridin-2-yl)-2-methoxyphenol,
4-(7-(2-fluoroethylamino)imidazo[1,2-a]pyridin-2-yl)phenol,
3-(7-(2-fluoroethylamino)imidazo[1,2-a]pyridin-2-yl)phenol,
N-(2-fluoroethyl)-2-(4-morpholin-4-ylphenyl)imidazo[1,2-a]pyridin-7-amine, and
N-cyclopropyl-2-[4-(3-fluoropropoxy)phenyl]imidazo[1,2-a]pyridin-7-amine, or a pharmaceutically acceptable salt thereof.

2. A compound of formula IB:

wherein
R 1 and R 2 form, together with the carbon atoms to which they are attached, a ring consisting of —OCH 2 CH 2 O—, OCH 2 O—, OCH 2 CH 2 CH 2 O— or —NHC(O)CH 2 O—;
R 3 is hydrogen or lower alkoxy;
R 4 is hydrogen or lower alkyl;
R 5 is lower alkyl, cycloalkyl, lower alkyl substituted by hydroxy or lower alkyl substituted by halogen,
R a is hydrogen or 3H;
R b is hydrogen, hydroxy or 3 H;
or a pharmaceutically acceptable acid addition salt, a racemic mixture or its corresponding enantiomer and/or optical isomers thereof.

3. A compound according to claim 2 , wherein the compound is selected from the group consisting of:
[2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
[2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-imidazo[1,2-a]pyridin-7-yl]-dimethyl-amine,
[2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-imidazo[1,2-a]pyridin-7-yl]-(2-fluoro-ethyl)-methyl-amine,
(2-benzo[1,3]dioxol-5-yl-imidazo[1,2-a]pyridin-7-yl)-methyl-amine,
(2-benzo[1,3]dioxol-5-yl-imidazo[1,2-a]pyridin-7-yl)-dimethyl-amine,
(2-benzo[1,3]dioxol-5-yl-imidazo[1,2-a]pyridin-7-yl)-(2-fluoro-ethyl)-methyl-amine,
(2-benzo[1,3]dioxol-5-yl-imidazo[1,2-a]pyridin-7-yl)-(2-fluoro-ethyl)-amine,
N-[2-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-imidazo[1,2-a]pyridin-7-yl]-methyl-amine,
6-(7-methylamino-imidazo[1,2-a]pyridin-2-yl)-4H-benzo[1,4]oxazin-3-one, and
2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-(2-fluoroethyl)imidazo[1,2-a]pyridin-7-amine, or a pharmaceutically acceptable salt thereof.

4. A compound of formula IC:

wherein
R 1 and R 2 form, together with the carbon atoms to which they are attached, a ring consisting of —OCH 2 CH 2 O—, OCH 2 O—, OCH 2 CH 2 CH 2 O— or —NHC(O)CH 2 O—;
R 3 is hydrogen or lower alkoxy;
R 4 and R 5 form, together with the nitrogen atom to which they are attached, a ring consisting of —CH 2 CH 2 CHRCH 2 CH 2 —, —CH 2 CHRCH 2 CH 2 —, —CH 2 CH 2 OCH 2 CH 2 —, —CH 2 C

Assignees

• Hoffmann La Roche

Inventors

• Borroni Edilio
• Gobbi Luca
• Honer Michael
• Knust Henner
• Koerner Matthias
• Muri Dieter

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• A61K49/00

  Preparations for testing in vivo · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title