1.
Bioorg Med Chem Lett
; 23(16): 4523-7, 2013 Aug 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-23850200
RESUMO
A series of potent non-acetylinic negative allosteric modulators of the metabotropic glutamate receptor 5 (mGlu5 NAMs) was developed starting from HTS screening hit 1. Potency was improved via iterative SAR, and physicochemical properties were optimized to deliver orally bioavailable compounds acceptable for in vivo testing. A lead molecule from the series demonstrated dose-dependent activity in the second phase of the rat formalin test from 30 mg/kg, and a preliminary PK/PD relationship was established.