title: Design and synthesis of novel diphenacoum-derived, conformation-restricted vitamin K 2,3-epoxide reductase inhibitors.
abstract: Two novel diphenacoum-derived analogues 5 and 6 are designed, synthesized and tested as potential vitamin K 2,3-epoxide reductase (VKOR) inhibitors. The inhibition studies indicated that 5 is a potent VKOR inhibitor, which confirmed that the replacement of the tetrahydronaphthalene on diphenacoum to a chroman functionality does not have a major impact on inhibition potency. The conformation-restricted compound 6 is a moderate inhibitor which may serve as a lead compound for further study of the mode of action of coumarin-type anticoagulants at the molecular level.
authors.affiliation: Department of Chemistry and Life Science Research Center, Tunghai University, 181, Taichung-Kang Road, Sec. 3, Taichung 407, Taiwan, ROC.
authors.forename: Ding-Uei
authors.initials: DU
authors.lastname: Chen
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Kuo
authors.forename: Ding-Yah
authors.initials: DY
authors.lastname: Yang
mesh_terms: D000818:Animals; D002417:Cattle; D003374:Coumarins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D064417:Vitamin K Epoxide Reductases
chemical_list: D003374:Coumarins; D004791:Enzyme Inhibitors; C504282:diphenacoum; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases