Shao Yi-Ming, Yang Wen-Bin, Kuo Tun-Hsun, Tsai Keng-Chang, Lin Chun-Hung, Yang An-Suei, Liang Po-Huang, Wong Chi-Huey
Genomics Research Center, Academia Sinica, No. 128, Section 2, Academia Road, Taipei 11529, Taiwan.
Bioorg Med Chem. 2008 Apr 15;16(8):4652-60. doi: 10.1016/j.bmc.2008.02.040. Epub 2008 Feb 15.
A series of trifluoromethyl ketones as SARS-CoV 3CL protease inhibitors was developed. The inhibitors were synthesized in four steps from commercially available compounds. Three different amino acids were explored in the P1-position and in the P2-P4 positions varying amino acids and long alkyl chain were incorporated. All inhibitors were evaluated in an in vitro assay using purified enzyme and fluorogenic substrate peptide. One of the inhibitors showed a time-dependent inhibition, with a K(i) value of 0.3 microM after 4h incubation.
开发了一系列作为严重急性呼吸综合征冠状病毒3CL蛋白酶抑制剂的三氟甲基酮。这些抑制剂由市售化合物经四步合成。在P1位探索了三种不同的氨基酸，并在P2 - P4位引入了不同的氨基酸和长烷基链。所有抑制剂均使用纯化酶和荧光底物肽在体外试验中进行评估。其中一种抑制剂表现出时间依赖性抑制，孵育4小时后的K(i)值为0.3微摩尔。
