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Quantitative structure-activity relationship of the 1,5-diarylpyrazole class of cyclooxygenase-2 selective inhibitors
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- Author:
- No author available
- Journal Title:
- JOURNAL OF THE FOURTH MILITARY MEDICAL UNIVERSITY
- Issue:
- 16
- DOI:
- 10.3321/j.issn:1000-2790.2003.16.026
- Key Word:
- 前列腺素内过氧化物合酶;选择性抑制剂;吡唑类;定量构效关系
Abstract： 目的: 探讨1,5-二芳基吡唑类环加氧酶-2选择性抑制剂分子结构与活性定量关系,建立反映该类化合物构效关系的数学模型,为进一步药物设计提供理论依据. 方法: 按类型衍化出的先导化合物,采用多元回归分析方法,将22个5-取代吡唑化合物的环加氧酶-1抑制活性,环加氧酶-2抑制活性和抑制选择性与化合物疏水性参数logP, 取代基电性参数ó,立体参数MR进行相关及定量构效分析. 结果: 得到3个反映该类抑制剂活性及选择性的定量构效关系(QSAR)方程:PIC50,COX-1=8.789838(1.7681)-0.4075925(0.1839)logP; PIC50,COX-2=6.437434(0.2322)+0.8844070(0.3487)logP-1.693330(0.5003)Σó; Ps=-61.18379(26.1091)+13.26386(5.56937)logP-0.6875092(0.29647)(logP)2. 结论: 环加氧酶抑制选择性与疏水性呈抛物线关系;5位苯环3,4位引入推电子基团或疏水性取代基,有利于提高该类化合物环加氧酶-2抑制活性. 所得QSAR方程可较好地预测该类化合物选择性抑制环加氧酶-2的活性.
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