The design and synthesis of sulfonamides as caspase-1 inhibitors

William G Harter; Hans Albrect; Kenneth Brady; Bradley Caprathe; James Dunbar; John Gilmore; Sheryl Hays; Catherine R Kostlan; Beth Lunney; Nigel Walker

doi:10.1016/j.bmcl.2003.10.065

The design and synthesis of sulfonamides as caspase-1 inhibitors

Bioorg Med Chem Lett. 2004 Feb 9;14(3):809-12. doi: 10.1016/j.bmcl.2003.10.065.

Authors

William G Harter¹, Hans Albrect, Kenneth Brady, Bradley Caprathe, James Dunbar, John Gilmore, Sheryl Hays, Catherine R Kostlan, Beth Lunney, Nigel Walker

Affiliation

¹ Chemistry Department, Pfizer Global Research and Development, 2800 Plymouth Rd, Ann Arbor, MI 48105, USA. william.harter@pfizer.com

PMID: 14741295
DOI: 10.1016/j.bmcl.2003.10.065

Abstract

A series of sulfonamides (1) has been prepared as inhibitors of interleukin-1beta converting enzyme (ICE), also known as caspase 1. These compounds were designed to improve potency by rigidifying the enzyme bound molecule through an intramolecular hydrogen bond. An X-ray crystal structure of a representative member of this series bound to the active site of ICE, confirms the presence of the hydrogen bonding interaction.

MeSH terms

Binding Sites
Caspase 1 / metabolism
Caspase Inhibitors*
Crystallography, X-Ray
Drug Design*
Humans
Hydrogen Bonding
Models, Molecular
Molecular Conformation
Molecular Structure
Serpins / chemical synthesis*
Serpins / pharmacology*
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / pharmacology*
Viral Proteins*

Substances

Caspase Inhibitors
Serpins
Sulfonamides
Viral Proteins
interleukin-1beta-converting enzyme inhibitor
Caspase 1