Structure‐Based Design and Synthesis of Highly Potent SARS‐CoV 3CL Protease Inhibitors
Yiming Shao, Wen‐Bin Yang, Hung‐Pin Peng, Min‐Feng Hsu, Keng‐Chang Tsai, Tun‐Hsun Kuo, Andrew H.‐J. Wang, Po‐Huang Liang, Chun‐Hung Lin, An‐Suei Yang, Chi‐Huey Wong · ChemBioChem · 2007
In a successful example of lead optimization by computer modeling prediction, computational technology was used to optimize a lead inhibitor (TL-3) of the SARS-CoV 3CL protease. A novel C2-symmetric diol (1) was then designed and synthesized, and displayed higher affinity than the original lead compound by one order of magnitude in its inhibition constant (0.6→0.073 μM). We believe that this approach has provided a platform for further lead optimization.