Design and synthesis of noncompetitive metabotropic glutamate receptor subtype 5 antagonists

Santosh S Kulkarni; Barbara Nightingale; Christina M Dersch; Richard B Rothman; Amy Hauck Newman

doi:10.1016/j.bmcl.2006.04.032

Design and synthesis of noncompetitive metabotropic glutamate receptor subtype 5 antagonists

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3371-5. doi: 10.1016/j.bmcl.2006.04.032. Epub 2006 May 5.

Authors

Santosh S Kulkarni¹, Barbara Nightingale, Christina M Dersch, Richard B Rothman, Amy Hauck Newman

Affiliation

¹ Medicinal Chemistry Section, National Institute on Drug Abuse, Intramural Research Program, NIH, DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA.

PMID: 16678408
DOI: 10.1016/j.bmcl.2006.04.032

Abstract

A series of diaryl amides was designed and synthesized as novel nonethynyl mGluR5 antagonists. The systematic variation of the pharmacophoric groups led to the identification of a lead compound that demonstrated micromolar affinity for the mGluR5. Further optimization resulted in compounds with improved binding affinities and antagonist profiles, in vitro.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Amides / chemical synthesis*
Amides / chemistry
Amides / pharmacology*
Animals
Binding Sites / drug effects
Cattle
Crystallography, X-Ray
Drug Design
Drug Evaluation, Preclinical
In Vitro Techniques
Ligands
Models, Molecular
Molecular Structure
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / antagonists & inhibitors*
Stereoisomerism
Structure-Activity Relationship

Substances

Amides
Ligands
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate

Grants and funding

Intramural NIH HHS/United States