Sinteza i antihipoksično djelovanje alifatskih i arilalifatskih amida kofein-8-tioglikolne kiseline

The synthesis of some aliphatic and arylaliphatic amides of caffeine-8-thioglycolic acid was studied. The structures of synthesized compounds were proved by microanalyses, IR- and 1H NMR data. Values of acute p.o. and i.p. toxicity in mice show lower toxicity compared to caffeine. Declines in spontaneous locomotor activity support the idea of depressive CNS activity of the compounds. Two compounds exhibited brain antihypoxic activity (5a and 5b against haemic and circulatory hypoxia, respectively).U radu je opisana sinteza alifatskih i arilalifatskih amida kofein-8-tioglikolne kiseline i njihova karakterizacija elementarnom analizom, IR- i 1H NMR spektroskopijom. Testiranja na miševima pokazuju da su sintetizirani spojevi primijenjeni p.o. i i.p. manje toksični od kofeina. Smanjenje lokomotoričke aktivnosti podupire ideju o njihovom depresivnom djelovanju na SŽS. Spojevi 5a i 5b djeluju antihipoksički u uvjetima krvne i cirkulacijske hipoksije u mozgu

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

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-#1086x#1086-2#1053-chromen-3-yl)-(2-#1077thoxycarbonylphenyl) methyl]-chromen-2-#1086ne (3) and 3-[2,6-dichlorophenyl) (#1077thoxy) methyl]-4- hydroxy- 2#1053-chromen-2-#1086ne (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