Nonsteroidal antiinflammatory agents-part 2 antiinflammatory, analgesic and antipyretic activity of some substituted 3-pyrazolin-5-ones and 1,2,4,5,6,7-3H-hexahydroindazol-3-ones.

摘要

As a part of a research project on the synthesis of a number of substituted 1-(pyrimidin-2-yl)-3-pyrazolin-5-ones and 2-(pyrimidin-2-yl)hexahydroindazol-3-ones and as a result of the interesting antiinflammatory, analgesic and antipyretic activities recorded for some of these compounds, some new 3-pyrazolin-5-ones and hexahydroindazol-3-ones linked to substituted imidazolyl, pyrimidyl and tetrahydroquinazolinyl moieties were prepared and evaluated for such activity (). A structure-activity relationship (SAR) comparative study indicated that some compounds from 3-pyrazolin-5-one (2, 6-8, 10) and indazolone (18, 20, 24, 27, 29) series exhibited pronounced antiinflammatory, analgesic and antipyretic activities relative to indomethacin. Most of these compounds were found to be nearly equipotent in the antiinflammatory screen (ED(50)=16.8-19.9 mg/kg) whereas the lead compound, 2-indazolyl-4-pyrimidineacetic acid 24 (), was found to be the most potent among this series (ED(50)=9.9 mg/kg). Additionally, the most active compounds were shown to have a large safety margin (ALD(50)=3.0 g/kg, po) and devoid of ulcerogenic potentialities when administered orally at a dose of 300 mg/kg.