Dipeptidyl aspartyl fluoromethylketones as potent caspase-3 inhibitors: SAR of the P2 amino acid

Yan Wang; Jin-Chen Huang; Zhang-Lin Zhou; Wu Yang; John Guastella; John Drewe; Sui Xiong Cai

doi:10.1016/j.bmcl.2003.12.065

Dipeptidyl aspartyl fluoromethylketones as potent caspase-3 inhibitors: SAR of the P2 amino acid

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1269-72. doi: 10.1016/j.bmcl.2003.12.065.

Authors

Yan Wang¹, Jin-Chen Huang, Zhang-Lin Zhou, Wu Yang, John Guastella, John Drewe, Sui Xiong Cai

Affiliation

¹ Maxim Pharmaceuticals, 6650 Nancy Ridge Drive, San Diego, CA 92121, USA.

PMID: 14980679
DOI: 10.1016/j.bmcl.2003.12.065

Abstract

This article describes the synthesis and biological evaluation of a series of dipeptidyl aspartyl fluoromethylketones as caspase-3 inhibitors. Structure-activity relationship (SAR) studies showed that for caspase-3 inhibition, Val is the best P(2) amino acid. The SAR studies also showed that the Asp free carboxylic acid in P(1) is important for caspase inhibiting activities, as well as for selectivity over other proteases.

MeSH terms

Aspartic Acid / chemistry
Caspase 3
Caspase Inhibitors*
Caspases / metabolism
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology*
Structure-Activity Relationship
Valine / chemistry

Substances

Caspase Inhibitors
Protease Inhibitors
Aspartic Acid
Caspase 3
Caspases
Valine