| Literature DB >> 16161992 |
Philip R Kym1, Rajesh Iyengar, Andrew J Souers, John K Lynch, Andrew S Judd, Ju Gao, Jennifer Freeman, Mathew Mulhern, Gang Zhao, Anil Vasudevan, Dariusz Wodka, Christopher Blackburn, Jim Brown, Jennifer Lee Che, Courtney Cullis, Su Jen Lai, Matthew J LaMarche, Tom Marsilje, Jon Roses, Todd Sells, Brad Geddes, Elizabeth Govek, Michael Patane, Dennis Fry, Brian D Dayton, Sevan Brodjian, Doug Falls, Michael Brune, Eugene Bush, Robin Shapiro, Victoria Knourek-Segel, Thomas Fey, Cathleen McDowell, Glenn A Reinhart, Lee C Preusser, Kennan Marsh, Lisa Hernandez, Hing L Sham, Christine A Collins.
Abstract
4-(1-Benzo[1,3]dioxol-5-ylmethylpiperidine-4-ylmethyl)-6-chlorochromen-2-one (7) is a potent, orally bioavailable melanin concentrating hormone receptor 1 (MCHr1) antagonist that causes dose-dependent weight loss in diet-induced obese mice. Further evaluation of 7 in an anesthetized dog model of cardiovascular safety revealed adverse hemodynamic effects at a plasma concentration comparable to the minimally effective therapeutic concentration. These results highlight the need for scrutiny of the cardiovascular safety profile of MCHr1 antagonists.Entities:
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Year: 2005 PMID： 16161992 DOI： 10.1021/jm050598r
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446