Dipeptidyl aspartyl fluoromethylketones as potent caspase-3 inhibitors: SAR of the P2 amino acid.
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.
Wang
Yan
Y
Maxim Pharmaceuticals, 6650 Nancy Ridge Drive, San Diego, CA 92121, USA.
Huang
Jin-Chen
JC
Zhou
Zhang-Lin
ZL
Yang
Wu
W
Guastella
John
J
Drewe
John
J
Cai
Sui Xiong
SX
D001224:Aspartic Acid / Q000737:chemistry; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014633:Valine / Q000737:chemistry
D061945:Caspase Inhibitors; D011480:Protease Inhibitors; D001224:Aspartic Acid; D053148:Caspase 3; D020169:Caspases; D014633:Valine