College of Pharmacy, Woosuk University, Wanju, Jeonbuk 565-701, South Korea.
Bioorg Med Chem. 2012 May 1;20(9):2860-8. doi: 10.1016/j.bmc.2012.03.028. Epub 2012 Mar 24.
A series of novel 4-O-methylhonokiol analogs were synthesized in light of revealing structure-activity relationship for inhibitory effect of COX-2 enzyme. The key strategy of the molecular design was oriented towards modification of the potential metabolic soft spots (e.g., phenol and olefin) or by altering the polar surface area via incorporating heterocycles such as isoxazole and triazole. Most of all exhibited the inhibitory effects on COX-2 and PGF(1) production but not macrophage NO production. Especially, aryl carbamates 10 and 11 exhibited more potent inhibitory activity against COX-2 and PGF(1) production.
为了揭示对 COX-2 酶抑制作用的构效关系，我们合成了一系列新型 4-O-甲基厚朴酚类似物。分子设计的关键策略是针对潜在代谢弱点（如酚和烯烃）进行修饰，或者通过引入异恶唑和三唑等杂环来改变极性表面积。所有化合物均表现出对 COX-2 和 PGF(1)产生的抑制作用，但对巨噬细胞 NO 产生没有影响。特别是芳基氨基甲酸酯 10 和 11 对 COX-2 和 PGF(1)的产生表现出更强的抑制活性。
