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.
Maxim Pharmaceuticals, 6650 Nancy Ridge Drive, San Diego, CA 92121, USA.
Yan
Y
Wang
Jin-Chen
JC
Huang
Zhang-Lin
ZL
Zhou
Wu
W
Yang
John
J
Guastella
John
J
Drewe
Sui Xiong
SX
Cai
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