| Literature DB >> 12930139 |
Yong-Jin Wu1, Carl D Davis, Steven Dworetzky, William C Fitzpatrick, David Harden, Huan He, Ronald J Knox, Amy E Newton, Thomas Philip, Craig Polson, Digavalli V Sivarao, Li-Qiang Sun, Svetlana Tertyshnikova, David Weaver, Suresh Yeola, Mary Zoeckler, Michael W Sinz.
Abstract
The formation of a reactive intermediate was found to be responsible for CYP3A4 metabolism-dependent inhibition (MDI) observed with (S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]-3-phenyl-acrylamide (1). Structure-3A4 MDI relationship studies culminated in the discovery of a difluoro analogue, (S)-N-[1-(4-fluoro-3-morpholin-4-ylphenyl)ethyl]-3-(4-fluoro-phenyl)acrylamide (2), as an orally bioavailable KCNQ2 opener free of CYP3A4 MDI.Entities:
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Year: 2003 PMID： 12930139 DOI： 10.1021/jm034111v
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446