Synthesis, structure, toxicological and pharmacological investigations of 4-hydroxycoumarin derivatives.
Twenty 4-hydroxycoumarin derivatives were synthesized. Five of them are described for the first time. The X-ray crystal structure analysis of 3,3'-(2,3,4-trimethoxyphenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) (7) and 3,3'-(3,5-dimethoxy-4-hydroxyphenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) (9) confirmed the structure of these compounds. A comparative pharmacological study of the anticoagulant effect with respect to Warfarin showed that the synthesized compounds have different anticoagulant activities. The most prospective compound is 3,3'-(4-chlorophenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) (12) with low toxicity, very good index of absorption and dose dependent anticoagulant activity.
Manolov
Ilia
I
Department of Organic Chemistry, Faculty of Pharmacy, Sofia, Bulgaria. imanolov@mbox.pharmfac.acad.bg
Maichle-Moessmer
Caecilia
C
Danchev
Nicolay
N
D015110:4-Hydroxycoumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001777:Blood Coagulation; D018360:Crystallography, X-Ray; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D015110:4-Hydroxycoumarins