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Synthesis and SAR of acyclic HCV NS3 protease inhibitors with novel P4-benzoxaborole moieties |
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| Authors: | Li Xianfeng Zhang Suoming Zhang Yong-Kang Liu Yang Ding Charles Z Zhou Yasheen Plattner Jacob J Baker Stephen J Bu Wei Liu Liang Kazmierski Wieslaw M Duan Maosheng Grimes Richard M Wright Lois L Smith Gary K Jarvest Richard L Ji Jing-Jing Cooper Joel P Tallant Matthew D Crosby Renae M Creech Katrina Ni Zhi-Jie Zou Wuxin Wright Jon |
| Institution: | a Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA b GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA c GlaxoSmithKline, Gunnels Wood Road, Stevenage, Herts, SG1 2NY, UK d Acme Bioscience, Inc., 3941 E. Bayshore Road, Palo Alto, CA 94303, USA e BioDuro LLC, Building E, No. 29, Life Science Park Road, Beijing 102206, PR China |
| Abstract: | We have synthesized and evaluated a new series of acyclic P4-benzoxaborole-based HCV NS3 protease inhibitors. Structure-activity relationships were investigated, leading to the identification of compounds 5g and 17 with low nanomolar potency in the enzymatic and cell-based replicon assay. The linker-truncated compound 5j was found to exhibit improved absorption and oral bioavailability in rats, suggesting that further reduction of molecular weight and polar surface area could result in improved drug-like properties of this novel series. |
| Keywords: | Synthesis and SAR Structure-activity relationships Benzoxaborole HCV NS3 protease Acyclic inhibitors |
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