Merck Research Laboratories, MSD, Newhouse, Lanarkshire, United Kingdom.
Bioorg Med Chem Lett. 2010 Dec 1;20(23):6890-4. doi: 10.1016/j.bmcl.2010.10.012. Epub 2010 Oct 26.
The trifluoromethylphenyl P2 motif from previously reported heteroarylnitrile series has been successfully applied for the design and synthesis of highly potent novel ketoamide-based cathepsin S inhibitors. The key in this process is the change of the torsion angle between the P2 phenyl ring and the attached secondary amide by adding a small Cl, F, or Me group at the 2-position.
先前报道的杂芳基腈系列中的三氟甲基苯 P2 基序已成功应用于设计和合成高活性新型酮酰胺基组织蛋白酶 S 抑制剂。在此过程中的关键是通过在 2 位添加一个小的 Cl、F 或 Me 基团，改变 P2 苯环与连接的二级酰胺之间的扭转角。
