title: Design, synthesis, and biological evaluation of 1,5-benzothiazepine-4-one derivatives targeting factor VIIa/tissue factor.
abstract: The 1,5-benzothiazepine-4-one scaffold was earlier shown to provide efficient protease inhibitors. In this contribution, we describe its use in the design of factor VIIa/tissue factor inhibitors. A series containing a scaffold non-substituted on its aryl part led to compound 20 with an IC(50) of 2.16 microM. Following molecular modelling studies of this compound, a second series was prepared, which necessitated the synthesis of protected 7- or 8-substituted 1,5-benzothiazepine-4-one derivatives.
authors.affiliation: Institut des Biomolécules Max Mousseron, CNRS UMR5247, Université Montpellier 1, Université Montpellier 2, Faculté de Pharmacie, 15 Avenue Charles Flahault, 34093 Montpellier Cedex 5, France.
authors.forename: Erwan
authors.initials: E
authors.lastname: Ayral
authors.forename: Philippe
authors.initials: P
authors.lastname: Gloanec
authors.forename: Gilbert
authors.initials: G
authors.lastname: Bergé
authors.forename: Guillaume
authors.initials: G
authors.lastname: de Nanteuil
authors.forename: Philippe
authors.initials: P
authors.lastname: Mennecier
authors.forename: Alain
authors.initials: A
authors.lastname: Rupin
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Verbeuren
authors.forename: Pierre
authors.initials: P
authors.lastname: Fulcrand
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Hernandez
mesh_terms: D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015942:Factor VIIa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D013841:Thiazepines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C106746:1,5-benzothiazepine; D013841:Thiazepines; D013925:Thromboplastin; D015942:Factor VIIa