title: Discovery of melanin-concentrating hormone receptor R1 antagonists using high-throughput synthesis.
abstract: 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.
authors.affiliation: Department of Chemical Research, Schering-Plough Research Institute K15 2545, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jing.su@spcorp.com
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Brian A
authors.initials: BA
authors.lastname: McKittrick
authors.forename: Haiqun
authors.initials: H
authors.lastname: Tang
authors.forename: Michael
authors.initials: M
authors.lastname: Czarniecki
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Brian E
authors.initials: BE
authors.lastname: Hawes
authors.forename: Kim
authors.initials: K
authors.lastname: O'Neill
mesh_terms: 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
chemical_list: D006727:Hormone Antagonists; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor