Synthesis, Toxicological, Anticoagulant Activity and Quantumchemical Study of Bis-coumarins and Other Coumarin Derivatives

Ilia Manolov, Ivan Dimitrov, Nikolai Danchev, Ivanka Kostadinova

Fifteen 4-hydroxycoumarin derivatives were synthesized. Seven of them are described for the first time. By means of X-ray crystal structure analysis of 4-hydroxy-3-[(2-оxо-2Н-chromen-3-yl)-(2-еthoxycarbonylphenyl) methyl]-chromen-2-оne (3) and 3-[2,6-dichlorophenyl) (еthoxy) methyl]-4- hydroxy- 2Н-chromen-2-оne (6) were confirmed the structure of these compounds previously by us. A comparative pharmacological study of the anticoagulant effect with respect to warfarin showed that the synthesized compounds have different anticoagulant activities. The QSTR model derived on the set of seventeen 4-hydroxycoumarin derivatives indicates that low i.p. toxicity could be achieved for a compound with large surface, unbranched molecule, with electronegative neighbour substituents and missing phydroxylgroup in the aldehyde fragment of the molecule.