title: Bicyclic[4.1.0]heptanes as phenyl replacements for melanin concentrating hormone receptor antagonists.
abstract: Melanin concentrating hormone (MCH) receptor antagonists have been proposed as potential treatments of obesity. MCH receptor antagonists with a biphenylamine subunit have been reported previously at Schering-Plough. Herein, we report the discovery of bicyclo[4.1.0]heptanes as replacements for the middle phenyl ring of the biphenylamine moiety in order to eliminate its potential mutagenic liability. Structure-activity relationships in this series were found to be very similar to those of the original biphenylamine series, suggesting that the two series have similar binding modes.
authors.affiliation: Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA. ruo.xu@spcorp.com
authors.forename: Ruo
authors.initials: R
authors.lastname: Xu
authors.forename: Shengjian
authors.initials: S
authors.lastname: Li
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Paruchova
authors.forename: Mark D
authors.initials: MD
authors.lastname: McBriar
authors.forename: Henry
authors.initials: H
authors.lastname: Guzik
authors.forename: Anandan
authors.initials: A
authors.lastname: Palani
authors.forename: John W
authors.initials: JW
authors.lastname: Clader
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cox
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Brian E
authors.initials: BE
authors.lastname: Hawes
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kowalski
authors.forename: Kim
authors.initials: K
authors.lastname: O'Neill
authors.forename: Brian D
authors.initials: BD
authors.lastname: Spar
authors.forename: Blair
authors.initials: B
authors.lastname: Weig
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weston
mesh_terms: D000611:Aminobiphenyl Compounds / Q000737:chemistry*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D002460:Cell Line; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D006536:Heptanes / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009153:Mutagens / Q000737:chemistry; D051381:Rats; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D000611:Aminobiphenyl Compounds; D001643:Bridged Bicyclo Compounds; D006536:Heptanes; D009153:Mutagens; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor