Synthesis and pharmacological investigations of some 4-hydroxycoumarin derivatives.
The synthesis of ten coumarin derivatives of 4-hydroxycoumarin and various unsaturated ketones and aldehydes is described. The structures of the synthesized compounds were confirmed by IR, (1)H-NMR, and mass-spectral data. Acute toxicity studies of the compounds were performed on mice by oral and intraperitoneal administration. A comparative pharmacological study of the in vivo anticoagulant effects of the derivatives with respect to warfarin, showed that the compounds have anticoagulant activity. Compounds 4-hydroxy-3-[1-phenyl-2-(4'-chlorobenzoyl)ethyl]-2H-1-benzopyran-2-one 2b, 4-hydroxy-3-[1-(4-fluorophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one 3a, and 3, 3'-p-bromobenzylidene-bis-(4-hydroxy-2H-1-benzopyran-2-one) 4b showed slight acute toxicity and a greater anticoagulant effect than warfarin.
Manolov
Ilia
I
Department of Industrial Pharmacy, Faculty of Pharmacy, Sofia, Bulgaria. imanolov@mbox.pharmfac.acad.bg
Danchev
Nicolay D
ND
D015110:4-Hydroxycoumarins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001777:Blood Coagulation / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D023382:Toxicity Tests, Acute
D015110:4-Hydroxycoumarins; D000925:Anticoagulants