(2S,4S)-amino-4-(2,2-diphenylethyl)pentanedioic acid selective group 2 metabotropic glutamate receptor antagonist.
(2S,4S)-2-Amino-4-(4,4-diphenylbut-1-yl)-pentane-1,5-dioic acid 1m, is a novel metabotropic glutamate receptor (mGluR) antagonist with insignificant ionotropic affinity. It is selective antagonist of negatively-coupled cAMP-linked mGluRs with no effect on phosphoinositide coupled mGluRs. A series of 4-substituted glutamic acid analogues were prepared and it was found that compound 1k is tenfold more potent than 1m. Compound 1k has neither significant affinity for ionotropic glutamate receptors nor group 1 and 3 metabotropic receptors.
Escribano
A
A
Centro de Investigación Lilly, Madrid, Spain.
Ezquerra
J
J
Pedregal
C
C
Rubio
A
A
Yruretagoyena
B
B
Baker
S R
SR
Wright
R A
RA
Johnson
B G
BG
Schoepp
D D
DD
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005971:Glutamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D007202:Indicators and Reagents; D015394:Molecular Structure; D010716:Phosphatidylinositols / Q000502:physiology; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C116622:2-amino-4-(2,2-diphenylethyl)pentanedioic acid; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D007202:Indicators and Reagents; D010716:Phosphatidylinositols; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D018698:Glutamic Acid; D000242:Cyclic AMP