The discovery of MK-0674, an orally bioavailable cathepsin K inhibitor

…, S Lamontagne, CK Lau, S Léger, T LeRiche…

文献索引：Isabel, Elise; Bateman, Kevin P.; Chauret, Nathalie; Cromlish, Wanda; Desmarais, Sylvie; Duong, Le T.; Falgueyret, Jean-Pierre; Gauthier, Jacques Yves; Lamontagne, Sonia; Lau, Cheuk K.; Leger, Serge; LeRiche, Tammy; Levesque, Jean-Francois; Li, Chun Sing; Masse, Frederic; McKay, Daniel J.; Mellon, Christophe; Nicoll-Griffith, Deborah A.; Oballa, Renata M.; Percival, M. David; Riendeau, Denis; Robichaud, Joel; Rodan, Gideon A.; Rodan, Sevgi B.; Seto, Carmai; Therien, Michel; Truong, Vouy Linh; Wesolowski, Gregg; Young, Robert N.; Zamboni, Robert; Black, W. Cameron Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 3 p. 887 - 892

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被引用次数: 18

摘要

MK-0674 is a potent and selective cathepsin K inhibitor from the same structural class as odanacatib with a comparable inhibitory potency profile against Cat K. It is orally bioavailable and exhibits long half-life in pre-clinical species. In vivo studies using deuterated MK-0674 show stereoselective epimerization of the alcohol stereocenter via an oxidation/reduction cycle. From in vitro incubations, two metabolites could be identified: ...