Substituted triazoles useful as mGlu5 receptor modulators
This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R 1 , R 2 , R 3 have meanings given in the description.
1. A compound of formula I
in which
A and B independently represent CH or N;
R 1 represents phenylethynyl, C 3-6 cycloalkylethynyl, C 2-5 alkenyl, C 5-7 cycloalkenyl, aryl, heteroaryl, C 1-8 alkyl, C 3-7 cycloalkyl or —O—C 1-8 alkyl which latter five groups are optionally substituted with one or more substituents selected from halogen, cyano, C 1-3 alkyl, C 3-6 cycloalkyl, —O—C 1-3 alkyl, —CH 2 —O—CH 3 , —CH 2 -morpholine and —CH 2 CN which latter six substituents are optionally substituted with one or more fluorine atoms;
R 2 and R 3 independently represent —H, halogen,—CN, —COO—C 1-4 alkyl, C 1-5 alkyl, C 3-5 cycloalkyl or —O—C 1-5 alkyl which latter four groups are optionally substituted with one or more fluorine atoms;
Ar represents;
or a physiologically acceptable salt thereof.
2. The compound according to claim 1 , wherein
R 1 represents phenylethynyl, cyclohexylethynyl, C 2-4 alkenyl, C 5-6 cycloalkenyl, phenyl, furyl, C 1-5 alkyl or C 3-6 cycloalkyl which latter four groups are optionally substituted with one or more substituents selected from fluoro, chloro, cyano, —CH 2 -morpholine, —CH 2 —O—CH 3 , —CH 2 CN, C 1-3 alkyl, C 3-6 cycloalkyl and —O—C 1-3 alkyl which latter three substituents are optionally substituted with one or more fluorine atoms.
3. The compound according to claim 1 , wherein
A represents N or CH;
B represents CH.
4. The compound according to claim 3 , wherein the group
represents
phenyl or 2-pyridyl which latter two groups are optionally substituted with one or two substituents selected from fluoro, chloro, bromo, —CN and C 1-3 alkyl optionally substituted with one or more fluorine atoms.
5. The compound according to claim 1 , namely a compound of formula I
in which
R 1 represents phenylethynyl, cyclohexylethynyl, C 2-4 alkenyl, C 5-6 cycloalkenyl, phenyl, furyl, C 1-5 alkyl or C 3-6 cycloalkyl which latter four groups are optionally substituted with one or more substituents selected from fluoro, chloro, cyano, —CH 2 -morpholine, —CH 2 —CH 3 , —CH 2 CN, C 1-3 alkyl, C 3-6 cycloalkyl and —O—C 1-3 alkyl which latter three substituents are optionally substituted with one or more fluorine atoms;
and the group
represents
phenyl or 2-pyridyl which latter two groups are optionally substituted with one or two substituents selected from fluoro, chloro, bromo, —CN and C 1-3 alkyl optionally substituted with one or more fluorine atoms;
or a physiologically acceptable salt thereof.
6. The compound according to claim 5 , wherein
R 1 represents phenyl, methyl, ethyl, propyl, iso-propyl, n-butyl, n-pentyl, cyclopentyl, cyclohexyl,
7. The compound according to claim 6 , wherein the group
represents
8. The compound according to claim 1 , namely a compound of formula I
in which
R 1 represents phenyl, methyl, ethyl, propyl, iso-propyl, n-butyl, n-pentyl, cyclopentyl, cyclohexyl,
Ar represents
the group
represents
or a physiologically acceptable salt thereof.
9. A compound selected from
or a physiologically acceptable salt thereof.
10. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable adjuvant, diluent and/or carrier.