Synthesis and X-ray crystal structures of substituted fluorobenzene and benzoquinone inhibitors of the tissue factor VIIa complex.

作者信息

Parlow John J, Kurumbail Ravi G, Stegeman Roderick A, Stevens Anna M, Stallings William C, South Michael S

机构信息

Department of Medicinal and Combinatorial Chemistry, Pharmacia Corporation, 800 North Lindbergh Boulevard, St. Louis, MO 63167, USA.

出版信息

Bioorg Med Chem Lett. 2003 Nov 3;13(21):3721-5. doi: 10.1016/j.bmcl.2003.08.002.

DOI:10.1016/j.bmcl.2003.08.002

PMID:14552766

Abstract

Multistep syntheses of substituted benzenes and benzoquinone inhibitors of tissue Factor VIIa are reported. The benzene analogues were designed such that their substitution pattern would occupy and interact with the S(1), S(2), and S(3) pockets of the tissue Factor VIIa (TF/VIIa) enzyme. The compounds exhibited modest potency on TF/VIIa with selectivity over Factor Xa and thrombin. The X-ray crystal structures of the targeted fluorobenzene 12a and benzoquinone 14 inhibitors bound to TF/VIIa were obtained and will be described.

摘要