Phenylethynyl and styryl derivatives of imidazole and fused ring heterocycles
This invention relates to a compound and the use of the compound of the formula wherein R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the description, A signifies —CH═CH— or —C≡C—; and B signifies wherein R 6 to R 26 , X and Y are as defined in the specification or a pharmaceutically acceptable salt thereof, for use in pharmaceutical compositions for the treatment or prevention of mGluR5 receptor mediated disorders.
1. A compound of formula
wherein
R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, lower alkyl, —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, or aryl;
R, R′ and R″ are independently selected from the group consisting of hydrogen and lower alkyl;
R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;
R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, and nitro; and
R 8 is selected from the group consisting of hydrogen, lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ or aryl;
or a pharmaceutically acceptable salt thereof.
2. A compound according to claim 1 , wherein R 7 signifies lower alkyl or —(CH 2 ) n —C(O)OR′.
3. The compound according to claim 1 , which is 4,5-diisopropyl-1-methyl-2-styryl-1H-imidazole.
4. The compound according to claim 1 , which is 2-[2-(4-fluoro-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole.
5. The compound according to claim 1 , which is 2-[2-(4-chloro-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole.
6. The compound according to claim 1 , which is 2-[2-(4-butoxy-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole.
7. The compound according to claim 1 , which is 4,5-diisopropyl-2-[2-(4-methoxy-2,3,6-trimethyl-phenyl)-vinyl]-1-methyl-1H-imidazole.
8. The compound according to claim 1 , which is 4,5-diisopropyl-2-[2-(4-methoxy-phenyl)-vinyl]-1-methyl-1H-imidazole.
9. The compound according to claim 1 , which is 2-[2-(4-chloro-3-fluoro-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole.
10. The compound according to claim 1 , which is 2-[2-(4-ethoxy-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole.
11. The compound according to claim 1 , which is 4,5-diisopropyl-1-methyl-2-[2-(2,3,4-trimethoxy-phenyl)-vinyl]-1H-imidazole.
12. The compound according to claim 1 , which is 2-[2-(2,4-dichloro-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole.
13. The compound according to claim 1 , which is 4,5-diisopropyl-1-methyl-2-(2-p-tolyl-vinyl)-1H-imidazole.
14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula
wherein
R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group consisting of hydrogen, lower alkyl, —(CH 2 ) n -halogen, lower alkoxy, —(CH 2 ) n —NRR′, —(CH 2 ) n —N(R)—C(O)-lower alkyl, or aryl;
R, R′ and R″ are independently selected from the group consisting of hydrogen and lower alkyl;
R 6 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR and halogen;
R 7 is selected from the group consisting of lower alkyl, —(CH 2 ) n —C(O)OR′, halogen, and nitro; and
R 8 is selected from the group consisting of hydrogen, lower alkyl, —(CH 2 ) n —OH, —(CH 2 ) n —C(O)OR″ or aryl;
or a pharmaceutically acceptable salt thereof in a racemic or optically active form and a pharmaceutically inert carrier.
15. A pharmaceutical composition according to claim 14 wherein the compound is selected from the group consisting of
4,5-diisopropyl-1-methyl-2-styryl-1H-imidazole,
2-[2-(4-fluoro-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole,
2-[2-(4-chloro-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole,
2-[2-(4-butoxy-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole,
4,5-diisopropyl-2-[2-(4-methoxy-2,3,6-trimethyl-phenyl)-vinyl]-1-methyl-1H-imidazole,
4,5-diisopropyl-2-[2-(4-methoxy-phenyl)-vinyl]-1-methyl-1H-imidazole,
2-[2-(4-chloro-3-fluoro-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole,
2-[2-(4-ethoxy-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole,
4,5-diisopropyl-1-methyl-2-[2-(2,3,4-trimethoxy-phenyl)-vinyl]-1H-imidazole,
2-[2-(2,4-dichloro-phenyl)-vinyl]-4,5-diisopropyl-1-methyl-1H-imidazole and
4,5-diisopropyl-1-methyl-2-(2-p-tolyl-vinyl)-1H-imidazole.
16. A pharmaceutical composition according to claim 14 wherein the compound is 4,5-diisopropyl-1-methyl-2-[2-(2,3,4-trimethoxy-phenyl)-vinyl]-1H-imidazole.