A series of structurally diverse N-[1-(6′-chloropyridazin-3′-yl)-3-(4″-substitutedphenyl)-1H-pyrazole-5-yl]alkanamides 5(a–r) has been designed and synthesized via Aliquat 336 catalyzed amidation of 5-amino-3-aryl-1-(6′-chloropyridazin-3′-yl)pyrazoles 3(a–c). The target compounds were designed on basis of the results obtained from the study of Lipinski's rule of five and binding interactions with target protein 3LN1. Eventually, compounds 5(a–r) were screened for their in vitro anti-inflammatory action by using inhibition of albumin denaturation and membrane stabilization assay. It has been found that all the synthesized compounds obeyed Lipinski's rule of five (n_violations = 0–1) and showed weak to strong binding interactions with dock score range −8.0 to −9.9 kcal/mol. All alkanamides exhibited moderate to excellent activity as compared to the standard drug, Aspirin. Interestingly, the results indicated that the compound 5a may act as a promising medicinal lead as an anti-inflammatory agent for in vivo and clinical testing in future.

中文翻译：

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N-[1-(6'-chloropyridazin-3'-yl)-3-(4"-取代苯基)-1H-pyrazole-5-yl]alkanamides 作为抗炎剂的设计、合成和生物学评价

设计了一系列结构多样的N -[1-(6'-chloropyridazin-3'-yl)-3-(4"-取代苯基)-1 H -pyrazole-5-yl]alkanamides 5(a – r)并通过 Aliquat 336 催化 5-amino-3-aryl-1-(6'-chloropyridazin-3'-yl)pyrazoles 3(a – c)的酰胺化合成。目标化合物的设计基于从 Lipinski 的五法则和与目标蛋白 3LN1 的结合相互作用的研究中获得的结果。最终，化合物5(a – r)通过使用抑制白蛋白变性和膜稳定性测定来筛选它们的体外抗炎作用。已经发现，所有合成的化合物都遵守 Lipinski 的五规则（n_违反 = 0-1），并且在码头得分范围 -8.0 至 -9.9 kcal/mol 时显示出弱到强的结合相互作用。与标准药物阿司匹林相比，所有链烷酰胺都表现出中等至极好的活性。有趣的是，结果表明化合物5a可能作为一种有前途的药用先导剂作为抗炎剂用于体内和临床试验。