Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4).
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.
Williams
Richard
R
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Johnson
Kari A
KA
Gentry
Patrick R
PR
Niswender
Colleen M
CM
Weaver
Charles D
CD
Conn
P Jeffrey
PJ
Lindsley
Craig W
CW
Hopkins
Corey R
CR
D000494:Allosteric Regulation / Q000187:drug effects; D000495:Allosteric Site; D000813:Anilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000813:Anilides; D003509:Cyclohexanecarboxylic Acids; D018094:Receptors, Metabotropic Glutamate; C544970:VU 0155041; C108823:metabotropic glutamate receptor 4