Prasanna Sivaprakasam, Manivannan Elangovan, Chaturvedi Subash Chandra
School of Pharmacy, DAVV, Indore-452017, Madhya Pradesh, India.
Arch Pharm (Weinheim). 2004 Aug;337(8):440-4. doi: 10.1002/ardp.200400887.
Quantitative structure activity relationships (QSAR) for two unique series of centrally fused pyrazole ring systems have been studied for selective cyclooxygenase-2 inhibitory activity. Several statistically significant QSAR models were developed and suggest that hydrophobicity of entire molecules and a fluorine atom substitution at position 8 of the non benzene sulphonyl ring fused with central pyrazole core of series 1 compounds is crucial for improved COX-2 selectivity. Various structural and physicochemical stipulations to improve the inhibitory activities of the enzymes among individual series of compounds are also discussed. The conclusions derived may serve as an example to advance the design of new selective COX-2 inhibitors.
针对两类独特的中心稠合吡唑环系统，研究了其定量构效关系（QSAR）与选择性环氧化酶-2抑制活性之间的联系。构建了多个具有统计学意义的QSAR模型，结果表明，对于提高COX-2选择性而言，整个分子的疏水性以及与系列1化合物的中心吡唑核稠合的非苯磺酰环8位上的氟原子取代至关重要。文中还讨论了各类结构和物理化学条件对提高各系列化合物中酶抑制活性的作用。所得结论可为新型选择性COX-2抑制剂的设计提供参考。
