Synthesis of a Peptidomimetic HCMV Protease Inhibitor Library

The human cytomegalovirus (HCMV) protease catalyzes the maturational process of the herpes virus assembly protein and plays a key role during the manufacture of viral capsid, and so is an attractive target for potential anti-herpes-virus agents with novel structures and new mechanisms. In this work, a peptidomimetic skeleton was designed and a chemical library containing 32 compounds with different substitutions on the skeleton was prepared by the oxidation of a precursor library, which was constructed from four types of building blocks: 4 carboxylic acids, 2 amines, 2 aldehydes and 2 isocyanides, based on multicomponent condensation following liquid phase strategies. The syntheses of the key building block isocyanides are presented.