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.

Graphical abstractTwenty coumarin derivatives have been synthesized. The most prospective compound is 3,3′-(4-chlorophenylmethylene)bis-(4-hydroxy-2H-1-benzopyran-2-one) with low toxicity, very good index of absorption and dose-dependent anticoagulant activity in vivo.Figure optionsDownload full-size imageDownload as PowerPoint slide