Synthesis and anticoagulant activities of substituted 2,4-diketochromans, biscoumarins, and chromanocoumarins.
Different substituted 2,4-diketochromans, biscoumarins, and chromanocoumarins are the final products when 4-hydroxycoumarin and aromatic aldehydes containing hydroxyl group in o-, m,- or p-position condense in boiling ethanol. We synthesized 14 compounds. Three of them are described for the first time. The X-ray crystal structure analysis of 3-[6-oxo-(6H, 7H)-benzopyrano[4,3-b]benzopyran-7-yl]-4-hydroxy-2H-1-benzopyran-2-one 1 confirmed the structure of this compound. Acute toxicity studies of the compounds were performed on mice by oral and intraperitoneal administration. A comparative pharmacological study of the in vivo anticoagulant effect of the derivatives with respect to warfarin showed that the synthesized compounds have different anticoagulant activities. The most prospective compounds are 3-(3'-hydroxybenzylidene)-2,4-diketochroman 4 and 3,3'-(2-pyridylmethylene)-bis-4-hydroxy-2H-1-benzopyran-2-one 11 with low toxicity and dose-dependent anticoagulant activity in vivo.
Manolov
Ilia
I
Department of Organic Chemistry, Faculty of Pharmacy, Medical University, Sofia, Bulgaria. imanolov@mbox.pharmfac.acad.bg
Maichle-Moessmer
Caecilia
C
Nicolova
Irina
I
Danchev
Nicolay
N
D015110:4-Hydroxycoumarins / Q000138:chemical synthesis / Q000633:toxicity*; D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis / Q000633:toxicity*; D001777:Blood Coagulation / Q000187:drug effects*; D002839:Chromans / Q000138:chemical synthesis / Q000633:toxicity*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D015394:Molecular Structure; D014859:Warfarin / Q000633:toxicity; D014914:Whole Blood Coagulation Time
D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D002839:Chromans; D014859:Warfarin