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Synthesis 2002(8): 1017-1026
DOI: 10.1055/s-2002-31948
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of a Peptidomimetic HCMV Protease Inhibitor Library

Ping Xu*, Wenwei Lin, Xiaomin Zou
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100083, P. R. China
Fax: +86(010)62015584; e-Mail: pingxuzh@public.bta.net.cn ; e-Mail: pingxu@bjmu.edu.cn;
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Publication History

Received 31 January 2002
Publication Date:
03 June 2002 (online)

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Abstract

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.

Key words

combinatorial chemistry - condensation - antiviral agents - isocyanides - peptides

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