In the present work, a new series of 4-(1-(tert-butyl)-3-phenyl-1H-pyrazol-4-yl) pyridine possessing terminal ethyl or propyl sulfonamides was designed and synthesized. The cytotoxic effect of the final compounds was measured by applying MTT assay in LPS-Induced RAW264.7 macrophage cells. The final target compounds were screened for their anti-inflammatory effect through their ability to inhibit NO and PGE₂ production and cytokines production (TNF-α, IL-6, IL-1β) in LPS-induced RAW264.7 macrophage at 10 μM concentration. Compounds 8d, 9d, and 9k showed the highest inhibitory effect on NO production. Compounds 8d and 9k exhibited high PGE₂ inhibition with IC₅₀ values of 3.47, 2.54 μM, respectively. Compounds 8d and 9k exhibited high cytokines inhibition ≥60%. The most potent compounds 8d and 9k were tested to determine their effect on iNOS and COX-2 mRNA expression level. Compound 9k activity on iNOS and COX-2 proteins level, pro-inflammatory mediators and cytokines was determined and showed remarkable inhibition for both proteins level. Compounds 8d, 9k showed high binding affinity to COX-2 active site and exhibited similar binding interactions of the native ligand celecoxib.

在目前的工作中，设计并合成了一系列具有末端乙基或丙基磺酰胺的新系列 4-(1-(叔丁基)-3-苯基-1H-吡唑-4-基) 吡啶。通过在 LPS 诱导的 RAW264.7 巨噬细胞中应用 MTT 测定来测量最终化合物的细胞毒性作用。通过在 10 μM 浓度下抑制 LPS 诱导的 RAW264.7 巨噬细胞中NO 和 PGE ₂产生和细胞因子产生（TNF-α、IL-6、IL-1β）的能力，筛选最终目标化合物的抗炎作用. 化合物8d、9d和9k对NO产生的抑制作用最高。化合物8d和9k表现出高 PGE ₂抑制与 IC_{50 个}值分别为 3.47、2.54 μM。化合物8d和9k表现出≥60%的高细胞因子抑制。测试了最有效的化合物8d和9k，以确定它们对 iNOS 和 COX-2 mRNA 表达水平的影响。测定了化合物9k对 iNOS 和 COX-2 蛋白水平、促炎介质和细胞因子的活性，并显示出对两种蛋白水平的显着抑制。化合物8d、9k显示出对COX-2活性位点的高结合亲和力并显示出与天然配体塞来昔布相似的结合相互作用。