title: Synthesis and biological evaluation of C-3 aliphatic coumarins as vitamin K antagonists.
abstract: Since the discovery of Warfarin in the 1940s, the design of new warfarin-derived anticoagulants for rodent management has been challenging, with mainly structural modifications performed on the C3 position of the coumarin skeleton. In order to better understand the pharmacomodulation of such derivatives, we have synthesized a family of C3 (linear and branched) alkyl-4-hydroxycoumarins, which led to the identification of compounds 5e and 5f as potential short-term active anticoagulants.
authors.affiliation: Univ Lyon, Université Claude Bernard Lyon 1, Laboratoire de Catalyse, Synthèse et Environnement, Institut de Chimie et de Biochimie Moléculaires et Supramoléculaires, ICBMS-CNRS-UMR 5246, F-69622 Villeurbanne Cedex, France; USC 1233 RS2GP, VetAgro Sup, INRA, Univ Lyon, F-69280 Marcy l'Etoile, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Montagut-Romans
authors.affiliation: Univ Lyon, Institut National des Sciences Appliquées (INSA-Lyon), Laboratoire de Chimie Organique et Bioorganique, ICBMS-CNRS-UMR 5246, F-69621 Villeurbanne Cedex, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Boulven
authors.affiliation: Univ Lyon, Institut National des Sciences Appliquées (INSA-Lyon), Laboratoire de Chimie Organique et Bioorganique, ICBMS-CNRS-UMR 5246, F-69621 Villeurbanne Cedex, France.
authors.forename: Maïwenn
authors.initials: M
authors.lastname: Jacolot
authors.affiliation: Univ Lyon, Institut National des Sciences Appliquées (INSA-Lyon), Laboratoire de Chimie Organique et Bioorganique, ICBMS-CNRS-UMR 5246, F-69621 Villeurbanne Cedex, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Moebs-Sanchez
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, Univ Lyon, F-69280 Marcy l'Etoile, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Hascoët
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, Univ Lyon, F-69280 Marcy l'Etoile, France.
authors.forename: Abdessalem
authors.initials: A
authors.lastname: Hammed
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, Univ Lyon, F-69280 Marcy l'Etoile, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Besse
authors.affiliation: Univ Lyon, Université Claude Bernard Lyon 1, Laboratoire de Catalyse, Synthèse et Environnement, Institut de Chimie et de Biochimie Moléculaires et Supramoléculaires, ICBMS-CNRS-UMR 5246, F-69622 Villeurbanne Cedex, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lemaire
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, Univ Lyon, F-69280 Marcy l'Etoile, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Benoit
authors.affiliation: USC 1233 RS2GP, VetAgro Sup, INRA, Univ Lyon, F-69280 Marcy l'Etoile, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Lattard
authors.affiliation: Univ Lyon, Institut National des Sciences Appliquées (INSA-Lyon), Laboratoire de Chimie Organique et Bioorganique, ICBMS-CNRS-UMR 5246, F-69621 Villeurbanne Cedex, France. Electronic address: florence.popowycz@insa-lyon.fr.
authors.forename: Florence
authors.initials: F
authors.lastname: Popowycz
mesh_terms: D015110:4-Hydroxycoumarins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010836:Phytol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D011517:Prothrombin Time; D017207:Rats, Sprague-Dawley; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D064417:Vitamin K Epoxide Reductases / Q000037:antagonists & inhibitors*
chemical_list: D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D014812:Vitamin K; D010836:Phytol; C578519:VKORC1 protein, rat; D064417:Vitamin K Epoxide Reductases
keywords: 4-Hydroxycoumarin; C(3) alkylation; In vitro assay; In vitro test; Vitamin K