Synthesis of N(1)-substituted analogues of (2R,4R)-4-amino-pyrrolidine-2,4-dicarboxylic acid as agonists, partial agonists, and antagonists of group II metabotropic glutamate receptors.
The chemical synthesis of a series of N(1)-substituted derivatives of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylic acid [(2R,4R)-APDC] as constrained analogues of gamma-substituted glutamic acids is described. Appropriate substitution of the N(1)-position results in agonist, partial agonist, or antagonist activity at mGluR2, mGluR3, and/or mGluR6.
Mukhopadhyaya
J K
JK
Department of Neurology, Drug Discovery Program, Georgetown University Medical Center, 3900 Reservoir Road, N.W., 20007, Washington, DC, USA.
Kozikowski
A P
AP
Grajkowska
E
E
Pshenichkin
S
S
Wroblewski
J T
JT
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D018698:Glutamic Acid / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008024:Ligands; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology*; D017470:Receptors, Glutamate / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors*
D008024:Ligands; D011759:Pyrrolidines; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C113897:metabotropic glutamate receptor 6; D018698:Glutamic Acid