Guan Li-Ping, Xia Ya-Nan, Jin Qing-Hao, Liu Bing-Yu, Wang Si-Hong
Food and Pharmacy College, Zhejiang Ocean University Engineering Technology Research Center of Marine Biomedical Products, Zhejiang, Zhoushan 316022, PR China.
Food and Pharmacy College, Zhejiang Ocean University Engineering Technology Research Center of Marine Biomedical Products, Zhejiang, Zhoushan 316022, PR China.
Bioorg Med Chem Lett. 2017 Aug 1;27(15):3378-3381. doi: 10.1016/j.bmcl.2017.06.002. Epub 2017 Jun 3.
A series of (S)-N-substitued-1-phenyl-3,4-dihydroisoquinoline-2(1H)-carboxamide derivatives were designed, synthesized and evaluated for their anti-inflammatory and analgesic effects in vivo. Among the synthesized compounds 2a and 2n showed the best anti-inflammatory activity (inhibition rate: 95% and 92.7%, respectively) and analgesic effect (inhibition rate: 100% and 100%, respectively), which was greater than that or nearly equivalent to that of indomethacin. Compounds 2a and 2n were selected to test their inhibitory effects against ovine COX-1 and COX-2 using the cyclooxygenase inhibition assay in vitro. Compounds 2a and 2n are weak inhibitors of COX-1 isozyme but displayed moderate COX-2 isozyme inhibitory effects (IC=0.47μM and 1.63μM, respectively) and COX-2 selectivity indexes (SI=11.5 and 4.8). Furthermore, compound 2a was more inhibitors of COX-2 isozyme active than the reference drug celecoxib.
设计、合成了一系列(S)-N-取代-1-苯基-3,4-二氢异喹啉-2(1H)-甲酰胺衍生物，并对其体内抗炎和镇痛作用进行了评价。在合成的化合物中，2a和2n表现出最佳的抗炎活性（抑制率分别为95%和92.7%）和镇痛效果（抑制率分别为100%和100%），优于或几乎等同于吲哚美辛。选用化合物2a和2n，采用体外环氧化酶抑制试验检测其对绵羊COX-1和COX-2的抑制作用。化合物2a和2n是COX-1同工酶的弱抑制剂，但对COX-2同工酶显示出中等抑制作用（IC分别为0.47μM和1.63μM）和COX-2选择性指数（SI分别为11.5和4.8）。此外，化合物2a对COX-2同工酶活性的抑制作用比参比药物塞来昔布更强。
