Imidazopyridine derivatives
The present invention relates to compounds of general formula wherein Ar is phenyl or pyridinyl; X 1 is N or CH, X 2 is N or CH, with the proviso that only one of X 1 or X 2 is N and the other is CH; R 1 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, cyano or S(O) 2 -lower alkyl; R 2 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen or cyano; n is 1 or 2; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof. The compounds may be used for the treatment of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine and cocaine.
1. A compound of formula I
wherein
Ar is phenyl or pyridinyl;
X 1 is N or CH,
X 2 is N or CH, with the proviso that only one of X 1 or X 2 is N and the other is CH;
R 1 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, cyano or S(O) 2 -lower alkyl;
R 2 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen or cyano;
n is 1 or 2;
or a pharmaceutically acceptable acid addition salt, a racemic mixture or its corresponding enantiomer and/or optical isomers thereof.
2. The compound of formula IA-1 according to claim 1 ,
wherein
R 1 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, cyano or S(O) 2 -lower alkyl;
R 2 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen or cyano;
n is 1 or 2;
or a pharmaceutically acceptable acid addition salt, a racemic mixture or its corresponding enantiomer and/or optical isomers thereof.
3. The compound of formula IA-1 according to claim 1 , wherein the compound is selected from:
3-(4-Fluoro-phenyl)-6-[2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridine
3-(4-Chloro-phenyl)-6-[2-(4-chloro-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridine
6-[2-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-3-(4-fluoro-phenyl)-imidazo[1,2-a]pyridine
3-(4-Chloro-phenyl)-6-[2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridine
3-(4-Fluoro-phenyl)-6-(2-p-tolyl-2H-pyrazol-3-yl)-imidazo[1,2a]pyridine
3-Phenyl-6-(2-phenyl-2H-pyrazol-3-yl)-imidazo[1,2-a]pyridine
3-(4-Chloro-2-fluoro-phenyl)-6-[2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridine
3-Phenyl-6-(2-p-tolyl-2H-pyrazol-3-yl)-imidazo[1,2-a]pyridine
3-(4-Chloro-2-fluoro-phenyl)-6-[2-(4-chloro-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridine
6-[2-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-3-(4-methoxy-phenyl)-imidazo[1,2-a]pyridine
6-[2-(4-Fluoro-phenyl)-2H-pyrazol-3-yl]-3-(4-methoxy-phenyl)-imidazo[1,2-a]pyridine
3-(2,4-Difluoro-phenyl)-6-[2-(4-fluoro-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridine
6-[2-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-3-(2,4-difluoro-phenyl)-imidazo[1,2-a]pyridine
6-[2-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-3-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine
6-[2-(4-Fluoro-phenyl)-2H-pyrazol-3-yl]-3-(4-trifluoromethyl-phenyl)-imidazo[1,2-a]pyridine
4-{6-[2-(4-Fluoro-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridin-3-yl}-benzonitrile
4-{6-[2-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridin-3-yl}-benzonitrile
6-[2-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-3-(4-methanesulfonyl-phenyl)-imidazo[1,2-a]pyridine
6-[2-(4-Fluoro-phenyl)-2H-pyrazol-3-yl]-3-(4-methanesulfonyl-phenyl)-imidazo[1,2-a]pyridine
3-(4-Fluoro-phenyl)-6-[2-(4-trifluoromethyl-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridine or
4-{6-[2-(4-Trifluoromethyl-phenyl)-2H-pyrazol-3-yl]-imidazo[1,2-a]pyridin-3-yl}-benzonitrile.
4. The compound of formula IA-2 according to claim 1 ,
wherein
is a pyridine group, wherein the N-atom may be in 2, 3 or 4 position;
R 1 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, cyano or S(O) 2 -lower alkyl;
R 2 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen or cyano;
n is 1 or 2;
or a pharmaceutically acceptable acid addition salt, a racemic mixture or its corresponding enantiomer and/or optical isomers thereof.
5. The compound of formula IA-2 according to claim 1 , wherein the compound is selected from:
6-[2-(4-Fluoro-phenyl)-2H-pyrazol-3-yl]-3-pyridin-4-yl-imidazo[1,2-a]pyridine or
6-[2-(4-Chloro-phenyl)-2H-pyrazol-3-yl]-3-pyridin-4-yl-imidazo[1,2-a]pyridine.
6. The compound of formula B according to claim 1 ,
wherein
Ar is phenyl or pyridinyl;
R 1 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, cyano or S(O) 2 -lower alkyl;
R 2 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen or cyano;
n is 1 or 2;
or a pharmaceutically acceptable acid addition salt, a racemic mixture or its corresponding enantiomer and/or optical isomers thereof.
7. The compound of formula IB according to claim 1 , which compound is
3-(4-Fluoro-phenyl)-6-[3-(4-fluoro-phenyl)-3H-imidazol-4-yl]-imidazol[1,2-a]pyridine.
8. A process for the manufacture of a compound of formula I as defined in claim 1 , which process comprises
a) reacting a compound of formula
with a compound of formula
to a compound of formula
and, if desired, converting the compounds obtained into pharmaceutically acceptable acid addition salts.
b) reacting a compound of formula
with a compound of formula
to a compound of formula
and, if desired, converting the compounds obtained into pharmaceutically acceptable acid addition salts.
9. A compound according to claim 1 when manufactures by a process according to claim 8 .
10. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutical acceptable carrier and/or adjuvant.