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.