Discovery of Two Clinical Histamine H3 Receptor Antagonists: trans-N-Ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl) phenyl] cyclobutanecarboxamide (PF- …

…, BA Pettersen, AW Schmidt, DK Spracklin…

文献索引：Wager, Travis T.; Pettersen, Betty A.; Schmidt, Anne W.; Spracklin, Douglas K.; Mente, Scot; Butler, Todd W.; Howard, Harry; Lettiere, Daniel J.; Rubitski, David M.; Wong, Diane F.; Nedza, Frank M.; Nelson, Frederick R.; Rollema, Hans; Raggon, Jeffrey W.; Aubrecht, Jiri; Freeman, Jody K.; Marcek, John M.; Cianfrogna, Julie; Cook, Karen W.; James, Larry C.; Chatman, Linda A.; Iredale, Philip A.; Banker, Michael J.; Homiski, Michael L.; Munzner, Jennifer B.; Chandrasekaran, Rama Y. Journal of Medicinal Chemistry, 2011 , vol. 54, # 21 p. 7602 - 7620

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被引用次数: 28

摘要

The discovery of two histamine H3 antagonist clinical candidates is disclosed. The pathway to identification of the two clinical candidates, 6 (PF-036547 46) and 7 (PF-036547 64) 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 ...