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A novel series of metabotropic glutamate receptor 5 negative allosteric modulators based on a 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine core.

Abstract：

: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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Duvey G,Perry B,Le Poul E,Poli S,Bonnet B,Lambeng N,Charvin D,Donovan-Rodrigues T,Haddouk H,Gagliardi S,Rocher JP

doi

10.1016/j.bmcl.2013.06.044

subject

Has Abstract

pub_date

2013-08-15 00:00:00

pages

4523-7

issue

16

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00765-8

journal_volume

23

pub_type

杂志文章

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