Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs)

Darren W Engers; Colleen M Niswender; C David Weaver; Satyawan Jadhav; Usha N Menon; Rocio Zamorano; P Jeffrey Conn; Craig W Lindsley; Corey R Hopkins

doi:10.1021/jm9005065

Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs)

J Med Chem. 2009 Jul 23;52(14):4115-8. doi: 10.1021/jm9005065.

Authors

Darren W Engers¹, Colleen M Niswender, C David Weaver, Satyawan Jadhav, Usha N Menon, Rocio Zamorano, P Jeffrey Conn, Craig W Lindsley, Corey R Hopkins

Affiliation

¹ Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Abstract

We report the synthesis and evaluation of a series of heterobiaryl amides as positive allosteric modulators of mGluR4. Compounds 9b and 9c showed submicromolar potency at both human and rat mGluR4. In addition, both 9b and 9c were shown to be centrally penetrant in rats using nontoxic vehicles, a major advance for the mGluR4 field.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Allosteric Regulation
Amides / administration & dosage
Amides / chemistry*
Amides / pharmacokinetics
Amides / pharmacology*
Animals
Cell Line
Humans
Rats
Receptors, Metabotropic Glutamate / agonists*
Structure-Activity Relationship

Substances

Amides
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor 4

Abstract

Publication types

MeSH terms

Substances

Grants and funding