Discovery of melanin-concentrating hormone receptor R1 antagonists using high-throughput synthesis.
A structure-activity study on benzylpiperidine 1 was accomplished by utilizing high-throughput synthesis. Three focused libraries were designed and synthesized to quickly develop SAR. Further optimization led to the discovery of compound 2, an MCH receptor R1 antagonist with over 400-fold improvement in biological activity over the original lead.
Su
Jing
J
Department of Chemical Research, Schering-Plough Research Institute K15 2545, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jing.su@spcorp.com
McKittrick
Brian A
BA
Tang
Haiqun
H
Czarniecki
Michael
M
Greenlee
William J
WJ
Hawes
Brian E
BE
O'Neill
Kim
K
D006727:Hormone Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D006727:Hormone Antagonists; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor