El-Hawash Soad A M, Badawey El-Sayed A M, El-Ashmawey Ibrahim M
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt.
Eur J Med Chem. 2006 Feb;41(2):155-65. doi: 10.1016/j.ejmech.2005.09.006. Epub 2005 Dec 20.
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.
作为关于多种取代的1-(嘧啶-2-基)-3-吡唑啉-5-酮和2-(嘧啶-2-基)六氢吲唑-3-酮合成的研究项目的一部分，并且由于记录到其中一些化合物具有有趣的抗炎、镇痛和解热活性，制备了一些与取代的咪唑基、嘧啶基和四氢喹唑啉基部分相连的新型3-吡唑啉-5-酮和六氢吲唑-3-酮，并对其进行了此类活性评估()。构效关系(SAR)比较研究表明，3-吡唑啉-5-酮(2, 6 - 8, 10)和吲唑酮(18, 20, 24, 27, 29)系列中的一些化合物相对于吲哚美辛表现出显著的抗炎、镇痛和解热活性。在抗炎筛选中发现这些化合物中的大多数几乎具有同等效力(ED(50)=16.8 - 19.9 mg/kg)，而先导化合物2-吲唑基-4-嘧啶乙酸24()在该系列中被发现是最有效的(ED(50)=9.9 mg/kg)。此外，最具活性的化合物显示出较大的安全范围(ALD(50)=3.0 g/kg，口服)，并且以300 mg/kg的剂量口服给药时没有致溃疡的可能性。
