Peptidomimetic aminomethylene ketone inhibitors of interleukin-1 beta-converting enzyme (ICE).
Pyridone-based peptidomimetic inhibitors of recombinant human Interleukin-1 beta-converting enzyme (ICE, caspase-1) with an aminomethylene ketone activating group in the P1' position are described. Several analogues with sub-nanomolar Ki's versus ICE and improved aqueous solubility are reported.
Semple
G
G
Department of Medicinal Chemistry, Ferring Research Institute, Chilworth Research Centre, Southampton, U.K.
Ashworth
D M
DM
Batt
A R
AR
Baxter
A J
AJ
Benzies
D W
DW
Elliot
L H
LH
Evans
D M
DM
Franklin
R J
RJ
Hudson
P
P
Jenkins
P D
PD
Pitt
G R
GR
Rooker
D P
DP
Yamamoto
S
S
Isomura
Y
Y
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D012995:Solubility; D013329:Structure-Activity Relationship
D000577:Amides; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D011728:Pyridones; D011994:Recombinant Proteins