Pyrolle derivatives as positive allosteric modulators of...

C - Chemistry – Metallurgy – 07 – D

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C07D 413/14 (2006.01) A61K 31/415 (2006.01) A61K 31/4245 (2006.01) A61P 25/18 (2006.01) A61P 25/22 (2006.01) A61P 25/32 (2006.01) A61P 25/34 (2006.01) A61P 25/36 (2006.01) C07D 401/14 (2006.01)

Patent

CA 2608324

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 (C4-C7)cycloalkyl, (C3-C7)heterocycloalkyl , (C3- C7)heterocycloalkyl-(C1-C3)alkyl or (C3-C7)heterocycloalkenyl ring; P represents a (C5-C7)heteroeycloalkyl, (C5-C7)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, -NR8C(=O)-, -NR8C(=O)-O-, - NR8C(=O)-NR9, NR8S(=O)2-, -C(=O)NR8-, -O-C(=O)NR8-, -S-, -S(=O)-, -S(=O)2-, - S(C=O)2NR8-, -C(=O)-O-, -O-C(=O)-, -C(=NR8)NR9-, C(C=NOR8)NR9- , -NR8C(=NOR9)- , =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.

L'invention concerne de nouveaux composés qui sont des dérivés de pyrrole de formule (I) dans laquelle A, B, P, Q, W, R1 et R2 sont tels que définis dans la description. Les composés selon l'invention sont utiles dans la prévention ou le traitement des troubles du système nerveux central ou périphérique, et d'autres troubles modulés par les récepteurs mGluR5.

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