Center of Drug Discovery, China Pharmaceutical University, Nanjing, PR China.
Bioorg Med Chem Lett. 2010 Dec 15;20(24):7349-53. doi: 10.1016/j.bmcl.2010.10.056. Epub 2010 Oct 20.
Fourteen new 3-[4-(amino/methylsulfonyl)phenyl]methylene-indolin-2-one derivatives were synthesized. Six compounds displayed potent inhibitory activities against COX-1/2 and 5-LOX with IC(50) in the range of 0.10-9.87 μM. Particularly, 10f exhibited well balanced inhibitory action on these enzymes (IC(50)=0.10-0.56 μM). More importantly, 10f and several other compounds had comparable or stronger anti-inflammatory and analgesic activities, but better gastric tolerability in vivo, as compared with darbufelone mesilate and tenidap sodium. Therefore, our findings may aid in the design of new and safe anti-inflammatory reagents for the intervention of painful inflammatory diseases, such as rheumatoid arthritis at clinic.
合成了 14 种新型 3-[4-(氨基/甲磺酰基)苯基]亚甲基-吲哚啉-2-酮衍生物。其中 6 种化合物对 COX-1/2 和 5-LOX 表现出较强的抑制活性，IC50 值在 0.10-9.87 μM 范围内。特别地，化合物 10f 对这些酶具有良好的平衡抑制作用（IC50=0.10-0.56 μM）。更重要的是，与甲磺酸达布非隆和替尼达普钠相比，化合物 10f 和其他几种化合物在体内具有相当或更强的抗炎和镇痛活性，且胃耐受性更好。因此，我们的发现可能有助于设计新型安全的抗炎试剂，用于干预类风湿性关节炎等炎性疼痛疾病。
