新型 1,5-二芳基吡唑衍生物的合成、环氧化酶抑制、抗炎评价和致溃疡活性。
Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of new 1,5-diarylpyrazole derivatives.
机构信息
a Department of Pharmaceutical Organic Chemistry , Beni-Suef University , Beni-Suef , Egypt.
b Biochemistry Department, Cairo General Hospital , Cairo , Egypt , and.
出版信息
J Enzyme Inhib Med Chem. 2016;31(sup3):54-60. doi: 10.1080/14756366.2016.1201815. Epub 2016 Aug 10.
A new series of 1,5-diarylpyrazoles 10a-l was designed and synthesized for evaluation as COX inhibitors and as anti-inflammatory agents. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compound 10e was the most COX-2 selective compound (S.I. = 10.67) and the most potent anti-inflammatory derivative (ED = 46 μmol/kg) which is approximately 11-folds more potent than ibuprofen (ED = 499 μmol/kg) and had 2/3 potency of celecoxib (ED = 31 μmol/kg). All compounds were less ulcerogenic (ulcer indexes = 1.20-4.61) than ibuprofen (ulcer index = 20.25) and comparable to celecoxib (ulcer index = 2.90).
为了评估其作为 COX 抑制剂和抗炎药的效果，我们设计并合成了一系列新的 1,5-二芳基吡唑 10a-l。所有化合物对 COX-2 同工酶的选择性更高，并且具有良好的体内抗炎活性。化合物 10e 是最具 COX-2 选择性的化合物（S.I. = 10.67），也是最有效的抗炎衍生物（ED = 46 μmol/kg），其效力约为布洛芬（ED = 499 μmol/kg）的 11 倍，与塞来昔布（ED = 31 μmol/kg）的效力相当。所有化合物的致溃疡指数（ulcer indexes）均低于布洛芬（ulcer index = 20.25），与塞来昔布（ulcer index = 2.90）相当。
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