Cytomegalovirus protease inhibitors

Very recently, (3-lactam antibiotics have been shown to offer neuroprotection by increasing glutamate transporters expression via gene activation [15] in addition, the discoveries of new biologically active (3-lactams such as cholesterol acyl transferase inhibitors [16-18], thrombin inhibitors [19], human cytomegalovirus protease inhibitors [20], matrix-metallo protease inhibitors [21], inhibitors of human leukocyte elastase (HLE) [22, 23] and cysteine protease [24, 25], and apoptosis inductors [26, 27] have provided much needed motivation for continuous development of new (3-lactam systems. 

Another approach to a-ketoamide peptide mimetics was employed by Xu et al. [33] for the preparation of a human cytomegalovirus protease inhibitor library. In this case the oxidizable -OH group, protected as formate, belonged to the starting isocyanides. Thus, the reaction between N-acylated a-amino acids, amines, aldehydes, and isocyanides 42 afforded the a-hydroxyamides 43 in modest yields. Cleavage of the O-formyl bond was accomplished during the reaction by employing two... 

The strategy of using a post-Passerini O—>A -acyl transfer has also proven to be highly efficient for the synthesis of a cytomegalovirus protease inhibitor, and the N(10)-C(17) fragment of the cyclotheonamides (60), a series of important inhibitors of several trypsin-like serine proteases. ... 

Casado JL, Perez-Ehas MJ, Marti-Belda P, Antela A, Suarez M, Ciancas E et al. (1998) Improved outcome of cytomegalovirus retinitis in AIDS patients after introduction of protease inhibitors. J Acquir Immune Defic Syndr Hum Retrovirol 19 130-134 Catalano CE (2000) The terminase enzyme from bacteriophage lambda a DNA-packaging machine, Cell Mol Life Sci 57 128-148... 

Siegel, M.M., Tabei, K., Bebemitz, G.A., Baum, F.Z. Rapid methods for screening low molecular mass compounds non-covalently bound to proteins using size exclusion and mass spectrometry applied to inhibitors of human cytomegalovirus proteases. J. Mass Spectrom. 1998, 33, 264-273. 

A range of chiral (ly)-proline derivatives, for example 211, have been shown to be active serine protease inhibitors and are active antivirals of human cytomegalovirus (HCMV) <2003JME4428>. 

Veinberg G, Vorona M, Shestakova I, Kanepe I, Lukevics E (2003) Some of the more notable advances concern the development of mechanism-based serine protease inhibitors of elastase, cytomegalovirus protease, thrombin, prostate specific antigen, and cell metastasis and as inhibitors of acyl-CoA cholesterol acyl transferase. Curr Med Chem 10 1741... 

In 2002, Banfi and co-workers [39] further exploited this transformation to synthesize complex peptidomimetics exemplified by 29, a potent inhibitor of the serine proteases prolyl endo-peptidase [40] and Cytomegalovirus protease [41]. 

Siegel, M.M. Tabei, K. Bebernitz, G.A. Baum, E.Z. Rapid Methods for Screening Low Molecular Mass Compounds noncovalently Bound to Proteins Using Size Exclusion and Mass Spectrometry Applied to Inhibitors of Human Cytomegalovirus Protease, J. Mass Spectrom. 33, 264-273 (1998). 

Jenwitheesuk E, Samudrala R. Virtual screening of HIV-1 protease inhibitors against human cytomegalovirus protease using docking and molecular dynamics. AIDS 2005 19(5) 529-531. 

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