Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4).

Abstract

This Letter describes the synthesis and SAR of the novel positive allosteric modulator, VU0155041, a compound that has shown in vivo efficacy in rodent models of Parkinson's disease. The synthesis takes advantage of an iterative parallel synthesis approach to rapidly synthesize and evaluate a number of analogs of VU0155041.

• Authors: Richard Williams, Kari A Johnson, Patrick R Gentry, Colleen M Niswender, Charles D Weaver, P Jeffrey Conn, Craig W Lindsley, Corey R Hopkins
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 17 Pg. 4967-70 (Sep 01 2009) ISSN: 1464-3405 [Electronic] England
• PMID: 19640716 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anilides
• Cyclohexanecarboxylic Acids
• Receptors, Metabotropic Glutamate
• VU 0155041
• metabotropic glutamate receptor 4

Topics

• Allosteric Regulation (drug effects)
• Allosteric Site
• Anilides (chemical synthesis, chemistry, pharmacology)
• Animals
• Cyclohexanecarboxylic Acids (chemical synthesis, chemistry, pharmacology)
• Disease Models, Animal
• Parkinson Disease (drug therapy)
• Rats
• Receptors, Metabotropic Glutamate (chemistry, metabolism)
• Structure-Activity Relationship