Serine and threonine β-lactones: A new class of hepatitis A virus 3C cysteine proteinase inhibitors

MS Lall, YK Ramtohul, MNG James…

Index: Lall, Manjinder S.; Ramtohul, Yeeman K.; James, Michael N.G.; Vederas, John C. Journal of Organic Chemistry, 2002 , vol. 67, # 5 p. 1536 - 1547

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Citation Number: 95

Abstract

Hepatitis A virus (HAV) 3C enzyme is a cysteine proteinase essential for viral replication and infectivity and represents a target for the development of antiviral drugs. A number of serine and threonine β-lactones were synthesized and tested against HAV 3C proteinase. The dN- Cbz-serine β-lactone 5a displays competitive reversible inhibition with a K i value of 1.50× 10-6 M. Its enantiomer, lN-Cbz-serine β-lactone 5b is an irreversible inactivator with k ...