Design and synthesis of 3-arylpyrrolidine-2-carboxamide derivatives as melanocortin-4 receptor ligands.
Based on 3-phenylpropionamides, a series of 3-arylpyrrolidine-2-carboxamide derivatives was designed and synthesized to study the effect of cyclizations as melanocortin-4 receptor ligands. It was found that the 2R,3R-pyrrolidine isomer possessed the most potent affinity among the four stereoisomers.
Tran
Joe A
JA
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Tucci
Fabio C
FC
Arellano
Melissa
M
Jiang
Wanlong
W
Chen
Caroline W
CW
Marinkovic
Dragan
D
Fleck
Beth A
BA
Wen
Jenny
J
Foster
Alan C
AC
Chen
Chen
C
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001921:Brain / Q000187:drug effects; D003500:Cyclization; D015195:Drug Design; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D011759:Pyrrolidines; D044105:Receptor, Melanocortin, Type 4