Bisaril alquinilamidas as negative allosteric modulators of the metabotropic glutamate receptor 5 (mGluR5)

摘要

Pharmaceutical compositions containing compounds of Formula 1, and the use of compounds of Formula 1 for treating diseases and disorders including schizophrenia, paranoia, depression, Manic Depressive and anxiety.Claim 1: a compound of Formula 1 or a pharmaceutically acceptable Salt of the same, in which each W1, W2, W3, W5, W4, X1, X2, X3, X4, and Z1, Z2, Z3, Z4 and Z5 is selected independently between C, N, s and o; ------ is independently a simple link or a double Bond; N is 1 or 2; M is 0 OR 1; and P is 1 or 2; each of R1 and R2 are independently selected from h,Hydroxyl alkyl, halogeno, cyano, C1 -, Halo - C1 - 6 and - alkyl or alkyl C1 - 6); R3 is selected from h, halogen, alkyl of C1 - Halo - alkyl - 6, 6 - (C1, C1 alkyl or alkoxy -, Halo - 6) and hydroxyl C1 - 6; R4 and R5 are each independently selected from h, alkyl C1 - C3 - 6 6, cycloalkyl, aryl, Heteroaryl alkyl heteroariloxi, ariloxi, C1 -, 6 - nr7r8,The Group of formula (2) and alkyl groups C1 - C3 - 6 6, cycloalkyl, aryl, heteroaryl alkyl heteroariloxi, ariloxi, C1 -, 6 - and nr7r8 Group of formula (2) are optionally substituted alkyl with 1 to 4 independently C1 C1 Halo alkyl - 6, - 6, - - Oh or NH2; R4 and R5 and the Atoms to which They form a Ring; R6 is 1 to 4 groups.Each independently selected from h, halogen, oxo alkyl, cyano, C1 -, Halo - C1 - alkyl or alkyl C1 - 6, - 6), heterociclilo, NO2 and amino; and each of R7 and R8 is selected independently from h, alkyl C1 - 6Aryl and R7 and R8 can be taken together with nitrogen that are United to form a saturated Heterocycles containing 5-7 Atoms independently selected from 0, N, o or S.