| Literature DB >> 21928839 |
Travis T Wager1, Betty A Pettersen, Anne W Schmidt, Douglas K Spracklin, Scot Mente, Todd W Butler, Harry Howard, Daniel J Lettiere, David M Rubitski, Diane F Wong, Frank M Nedza, Frederick R Nelson, Hans Rollema, Jeffrey W Raggon, Jiri Aubrecht, Jody K Freeman, John M Marcek, Julie Cianfrogna, Karen W Cook, Larry C James, Linda A Chatman, Philip A Iredale, Michael J Banker, Michael L Homiski, Jennifer B Munzner, Rama Y Chandrasekaran.
Abstract
The discovery of two histamine H(3) antagonist clinical candidates is disclosed. The pathway to identification of the two clinical candidates, 6 (PF-03654746) and 7 (PF-03654764) required five hypothesis driven design cycles. The key to success in identifying these clinical candidates was the development of a compound design strategy that leveraged medicinal chemistry knowledge and traditional assays in conjunction with computational and in vitro safety tools. Overall, clinical compounds 6 and 7 exceeded conservative safety margins and possessed optimal pharmacological and pharmacokinetic profiles, thus achieving our initial goal of identifying compounds with fully aligned oral drug attributes, "best-in-class" molecules.Entities:
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Year: 2011 PMID： 21928839 DOI： 10.1021/jm200939b
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446