title: Biopotency of vitamin K. I. Antihemorrhagic properties of structural analogs of phylloquinone as determined by curative prothrombin time tests.
abstract: Relative antihemorrhagic properties of structural analogs of transphylloquinone (vitamin K1) have been determined by curative prothrombin time tests with vitamin K-deficient chicks. Analogs (where applicable) and the phylloquinone standard had (all-) rac-trans configuration, and all compounds were well characterized (structure, purity, trans: cis). Compounds were administered as single oral doses according to the up-and-down procedure. Estimation of mean effective doses allowed a reliable calculation of relative activities for analogs in comparison with vitamin K1 standard. 2', 3'-Dihydro-phylloquinone had a relative activity of only 6.7%, i.e. it was about 15 times less active than phylloquinone. Further reduction of this analog led to 2',3',5,6,7,8-hexahydro-phylloquinone which was completely inactive. Analogs with oxygen functions in the side chain, 6'-hydroxy-K1, 6'-oxo-K1, and 7'-hydroxy-6'-oxo-K1, displayed relative activities of 20.5%, 31.9%, and 30.5%, respectively. Phylloquinone-2,3-epoxide was 1.7 times more active than the phylloquinone standard. An analog with a 7-carbon side chain ending with a carboxy group (in mammals a urinary metabolite of vitamin K1) and its corresponding ethyl ester derivative were practically inactive.
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005260:Female; D006470:Hemorrhage / Q000188:drug therapy*; D011517:Prothrombin Time; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000494:pharmacology; D014813:Vitamin K Deficiency / Q000188:drug therapy
chemical_list: D014812:Vitamin K