Bioorganic & Medicinal Chemistry Letters 2008-01-15

Potency and selectivity of P2/P3-modified inhibitors of cysteine proteases from trypanosomes.

Priyadarshini Jaishankar, Elizabeth Hansell, Dong-Mei Zhao, Patricia S Doyle, James H McKerrow, Adam R Renslo

Index: Bioorg. Med. Chem. Lett. 18(2) , 624-8, (2008)

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Abstract

A systematic study of P2 and P3 substitution in a series of vinyl sulfone cysteine protease inhibitors is described. The introduction of a methyl substituent in the P2 phenylalanine aryl ring had a favorable effect on protease inhibition and conferred modest selectivity for rhodesain over cruzain. Rhodesain selectivity could be enhanced further by combining these P2 modifications with certain P3 amide substituents.