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
| Autor: | El-Sayed A. M. Badawey, Ibrahim M. El-Ashmawey, Soad A.M. El-Hawash |
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| Rok vydání: | 2006 |
| Předmět: |
Stereochemistry
Carboxylic acid Indomethacin Analgesic Administration Oral Pharmacology Chemical synthesis Lethal Dose 50 Structure-Activity Relationship chemistry.chemical_compound Oral administration Drug Discovery medicine Animals Edema Stomach Ulcer Antipyretic Pain Measurement chemistry.chemical_classification Bicyclic molecule Chemistry Anti-Inflammatory Agents Non-Steroidal Organic Chemistry General Medicine Analgesics Non-Narcotic Rats Toxicity Pyrazoles Lead compound medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 41:155-165 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2005.09.006 |
| Popis: | 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 ( Fig. 1 ). 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 ( Fig. 1 ), 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. |
| Databáze: | OpenAIRE |
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