Synthesis and SAR of a MGluR5 Allosteric Partial Antagonist Lead: Unexpected Modulation of Pharmacology with Slight Structural Modifications to a 5-(phenylethynyl)pyrimidine Scaffold

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2008 Jun 14

PMID 18550372

Citations 46

Authors

Sameer Sharma

Alice L Rodriguez

P Jeffrey Conn

Craig W Lindsley

Affiliations

Soon will be listed here.

Abstract

This Letter describes the synthesis and SAR, developed through an iterative analogue library approach, of a mGluR5 allosteric partial antagonist lead based on a 5-(phenylethynyl)pyrimidine scaffold. With slight structural modifications to the distal phenyl ring, analogues demonstrated a range of pharmacological activities from mGluR5 partial antagonism to full antagonism/negative allosteric modulation to positive allosteric modulation.

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