Bicyclic[4.1.0]heptanes as phenyl replacements for melanin concentrating hormone receptor antagonists.
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.
Xu
Ruo
R
Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA. ruo.xu@spcorp.com
Li
Shengjian
S
Paruchova
Jaroslava
J
McBriar
Mark D
MD
Guzik
Henry
H
Palani
Anandan
A
Clader
John W
JW
Cox
Kathleen
K
Greenlee
William J
WJ
Hawes
Brian E
BE
Kowalski
Timothy J
TJ
O'Neill
Kim
K
Spar
Brian D
BD
Weig
Blair
B
Weston
Daniel J
DJ
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
D000611:Aminobiphenyl Compounds; D001643:Bridged Bicyclo Compounds; D006536:Heptanes; D009153:Mutagens; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor