PHENYL-3-{(3-(1H-PYRROL-2-YL)-1, 2 , 40XADIAZ0L-5-YLPIPERIDIN- 1-YL}-METHANONE DERIVATIVES AND RELATED COMPOUNDS AS POSITIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS.

摘要

The present invention provides new compounds of formula (I) as positive allosteric modulators of metabotropic receptors - subtype 5 ("mGluR5") which are useful for the treatment or prevention of central nervous system disorders such as for example, cognitive decline, both positive and negative symptoms in schizophrenia as well as other central or peripheral nervous system disorders in which the mGluR5 subtype of glutamate metabotropic receptor is involved. The invention is also directed to pharmaceutical compounds and compositions in the prevention or treatment of such diseases in which mGluR5 is involved. W represents (Csub4/sub-Csub7/sub)cycloalkyl, (Csub3/sub-Csub7/sub)heterocycloalkyl , (Csub3/sub-Csub7/sub)heterocycloalkyl-(Csub1/sub-C sub3/sub)alkyl or (Csub3/sub-Csub7/sub)heterocycloalkenyl ring; P represents a (Csub5/sub-Csub7/sub)heteroeycloalkyl, (Csub5/sub-Csub7/sub)heterocycloalkenyl ring or a heteroaryl group of formula (a), (b), (c), (d), (e), (f), (g), (h), (i). Q denotes a cycloalkyl, an aryl or heteroaryl group of formula (j), (k), (l), (m), (n). A is azo -N=N-, ethyl, ethenyl, ethynyl, -NRsub8/subC(=O)-, -NRsub8/subC(=O)-O-, -NRsub8/subC(=O)-NRsub9/sub, NRsub8/subS(=O)sub2/sub-, -C(=O)NRsub8/sub-, -O-C(=O)NRsub8/sub-, -S-, -S(=O)-, -S(=O)sub2/sub-, -S(C=O)sub2/subNRsub8/sub-, -C(=O)-O-, -O-C(=O)-, -C(=NRsub8/sub)NRsub9/sub-, C(C=NORsub8/sub)NRsub9/sub- , -NRsub8/subC(=NORsub9/sub)-, =N-O-, -O-N=CH- or a group aryl or heteroaryl of formula, (o), (p), (q), (r), (s), (t), (u), (v), (w), (x). The other substituents are defined in the claims.