The structural optimization of the molecules making them to fit into the active site pocket of COX-2 occupying the same space as covered by the natural substrate arachidonic acid helped in the emergence of compound 10 as an efficacious anti-inflammatory agent. Selective for COX-2 over COX-1, compound 10 exhibited IC50 0.02 µM for COX-2 and reversed acetic acid induced inflammation in rats by 73% when used at 10 mg kg-1 dose and the same dose of the compound also rescued the animals from inflammatory phase of formalin induced hyperalgesia. As evidenced by the results of molecular modeling studies supported by the nuclear Overhauser enhancement data, the appropriate geometry of the molecule in the active site pocket of COX-2 contributing to its H-bond/hydrophobic interactions with Ser530, Trp387 and Tyr385 seems responsible for the enzyme inhibitory activity of the compound.

中文翻译：

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先导分子的修饰：色氨酸和哌啶附加的三嗪类药物可逆转大鼠的炎症和痛觉过敏。

分子的结构优化使其适合于COX-2的活性位点口袋，占据了与天然底物花生四烯酸覆盖的空间相同的空间，有助于化合物10作为有效的消炎剂的出现。相对于COX-1，CO10-2具有选择性，对COX-2的IC50为0.02 µM，当以10 mg kg-1的剂量使用时，逆转乙酸引起的大鼠炎症反应的发生率为73％，相同剂量的化合物也可以挽救动物从福尔马林的炎症期诱发痛觉过敏。正如核Overhauser增强数据所支持的分子模型研究结果所证明的那样，COX-2活性位点口袋中分子的适当几何结构有助于其与Ser530的氢键/疏水相互作用，