Potent, orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors

…, N Mollova, K Leung, JW Chisholm, J Zablocki

文献索引：Koltun, Dmitry O.; Zilbershtein, Timur M.; Migulin, Vasily A.; Vasilevich, Natalya I.; Parkhill, Eric Q.; Glushkov, Andrei I.; McGregor, Malcolm J.; Brunn, Sandra A.; Chu, Nancy; Hao, Jia; Mollova, Nevena; Leung, Kwan; Chisholm, Jeffrey W.; Zablocki, Jeff Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 15 p. 4070 - 4074

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被引用次数: 23

摘要

Two structurally distinct series of SCD (Δ9 desaturase) inhibitors (1 and 2) have been previously reported by our group. In the present work, we merged the structural features of the two series. This led to the discovery of compound 5b (CVT-12,012) which is highly potent in a human cell-based (HEPG2) SCD assay (IC50= 6nM). This compound has 78% oral bioavailability in rats and is preferentially distributed into liver (76 times vs plasma) with ...