Synthesis and metabotropic glutamate receptor antagonist activity of N1-substituted analogs of 2R,4R-4-aminopyrrolidine-2,4-dicarboxylic acid.
A series of N1-substituted derivatives of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) has been prepared as constrained analogs of gamma-substituted glutamic acids and examined for their effects at recombinant metabotropic glutamate receptor (mGluR) subtypes in vitro. Appropriate substitution of the N1 position of 2R,4R-APDC resulted in the identification of a number of selective group II mGluR antagonists.
Valli
M J
MJ
Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Schoepp
D D
DD
Wright
R A
RA
Johnson
B G
BG
Kingston
A E
AE
Tomlinson
R
R
Monn
J A
JA
D006801:Humans; D006868:Hydrolysis; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D018129:Phosphatidylinositol Phosphates; D018094:Receptors, Metabotropic Glutamate; D011994:Recombinant Proteins; D011392:Proline