title: Synthesis and X-ray crystal structures of substituted fluorobenzene and benzoquinone inhibitors of the tissue factor VIIa complex.
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.
authors.affiliation: Department of Medicinal and Combinatorial Chemistry, Pharmacia Corporation, 800 North Lindbergh Boulevard, St. Louis, MO 63167, USA. john.j.parlow@pfizer.com
authors.forename: John J
authors.initials: JJ
authors.lastname: Parlow
authors.forename: Ravi G
authors.initials: RG
authors.lastname: Kurumbail
authors.forename: Roderick A
authors.initials: RA
authors.lastname: Stegeman
authors.forename: Anna M
authors.initials: AM
authors.lastname: Stevens
authors.forename: William C
authors.initials: WC
authors.lastname: Stallings
authors.forename: Michael S
authors.initials: MS
authors.lastname: South
mesh_terms: D016227:Benzoquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015942:Factor VIIa / Q000037:antagonists & inhibitors*; D005464:Fluorobenzenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D007659:Ketones; D008958:Models, Molecular; D013379:Substrate Specificity
chemical_list: D016227:Benzoquinones; D005464:Fluorobenzenes; D007202:Indicators and Reagents; D007659:Ketones; D015942:Factor VIIa