Kobzar N. Synthesis, structure and biological activity of brom- and sulfamoyl substitute of ortho-chlorobenzoic, N-R-anthranilic acids and their derivatives

With the purpose of searching the new biologically active substances the new groups of compounds of 5-brom-2-chlorobenzoic, 5-brom-N-R-anthranilic acids derivatives and their 3-sulfamoyl substitutes have been synthesized. The preparative synthesis procedures of 3-oxo-1,2-dihydroindazole and N-phenylanthranilic acids brom- and 3-sulfamoyl- derivatives and the express quatification method of new N-phenylanthranilic acids by the biphase titration method in the octanol - water system have been proposed. The structure and individuality of the substances synthesized have been confirmed by the ultimate analysis, IR-, UV-, NMR-spectroscopy, chromato-mass spectrometry, counter synthesis, qualitative reactions data, and thin-layer chromatography. According to the results of the biological screening the substances, which reveal a high anti-inflamatory, analgesic, diuretic, hypoglycemic, bacteriostatic, fungistatic activity, as well as hypotoxicity, have been found among the compounds synthesized. A number of regularities of the "structure - activity - toxicity " relationship have been determined. 5-Brom-N-(2'-carboxy-4'-bromphenyl)anthranilic acid, which reveals a high analgesic, anti-inflamatory, diuretic and fungistatic activity with a low toxicity, has been patented and recommended for further pre-clinical trials. 1,8,8-trimethyl-3-(4-оxо-2-alkyl(aryl)-3,4-dihydroquinazolin-3-il)-3-azabicyclo[3.2.1]-octan-2,4-diones has been determined. For the first time the method of formation quinazolin-4(3H)-ones by the reaction anthranilamide with ?-diketones has been discovered. The hypoglycemic, diuretic, antimicrobic, anticoagulatic, hemostatic, anticonvulsive screening of the synthesized compounds has been conducted. The "structure - activity" relationship for these types of activities have been determined. According to the results of biological assay two low-toxic substances 3-[2-(2-(5-bromothiophene-2-yl)-2-oxoеthylthio)-4-oxo-3,4-dihydroquin-azo-lin-3-yl]-1,8,8-tri-me-thyl-3-azabicyclo[3.2.1]octan-2,4-dione (with hipoglicemic activity) and 3-[2-(2-(3-nitrophenyl)-2-oxoеthylthio)-4-oxo-3,4-dihydroquin-azo-lin-3-yl]-1,8,8-tri-me-thyl-3-azabicyclo[3.2.1]octan-2,4-dione (with high anticonvulsive activity) has been recommended for profound pharmacological study.