Peptidomimetic aminomethylene ketone inhibitors of interleukin-1 beta-converting enzyme (ICE)

G Semple; D M Ashworth; A R Batt; A J Baxter; D W Benzies; L H Elliot; D M Evans; R J Franklin; P Hudson; P D Jenkins; G R Pitt; D P Rooker; S Yamamoto; Y Isomura

doi:10.1016/s0960-894x(98)00136-x

Peptidomimetic aminomethylene ketone inhibitors of interleukin-1 beta-converting enzyme (ICE)

Bioorg Med Chem Lett. 1998 Apr 21;8(8):959-64. doi: 10.1016/s0960-894x(98)00136-x.

Authors

G Semple¹, D M Ashworth, A R Batt, A J Baxter, D W Benzies, L H Elliot, D M Evans, R J Franklin, P Hudson, P D Jenkins, G R Pitt, D P Rooker, S Yamamoto, Y Isomura

Affiliation

¹ Department of Medicinal Chemistry, Ferring Research Institute, Chilworth Research Centre, Southampton, U.K.

PMID: 9871520
DOI: 10.1016/s0960-894x(98)00136-x

Abstract

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.

MeSH terms

Amides / chemical synthesis*
Amides / chemistry
Amides / pharmacology
Caspase Inhibitors*
Cysteine Proteinase Inhibitors / chemical synthesis*
Cysteine Proteinase Inhibitors / chemistry
Cysteine Proteinase Inhibitors / pharmacology
Humans
Kinetics
Molecular Structure
Pyridones / chemical synthesis*
Pyridones / chemistry
Pyridones / pharmacology
Recombinant Proteins / antagonists & inhibitors
Solubility
Structure-Activity Relationship

Substances

Amides
Caspase Inhibitors
Cysteine Proteinase Inhibitors
Pyridones
Recombinant Proteins