Solid-phase synthesis of benzisothiazolones as serine protease inhibitors

K L Yu; R Civiello; D G Roberts; S M Seiler; N A Meanwell

doi:10.1016/s0960-894x(99)00078-5

Solid-phase synthesis of benzisothiazolones as serine protease inhibitors

Bioorg Med Chem Lett. 1999 Mar 8;9(5):663-6. doi: 10.1016/s0960-894x(99)00078-5.

Authors

K L Yu¹, R Civiello, D G Roberts, S M Seiler, N A Meanwell

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, Department of Chemistry, Wallingford, CT 06492, USA.

PMID: 10201825
DOI: 10.1016/s0960-894x(99)00078-5

Abstract

An efficient solid-phase synthesis of benzisothiazolone-1,1-dioxide-based serine protease inhibitors involving alkylation of carboxylic acids with N-(bromomethyl)benzisothiazolone-1,1-dioxide has been developed. An example using this procedure for preparation of a library of human mast cell tryptase inhibitors is described.

MeSH terms

Chymases
Humans
Mast Cells / drug effects
Mast Cells / enzymology
Serine Endopeptidases / metabolism
Serine Proteinase Inhibitors / chemical synthesis*
Serine Proteinase Inhibitors / chemistry
Serine Proteinase Inhibitors / pharmacology
Thiazoles / chemical synthesis*
Thiazoles / chemistry
Thiazoles / pharmacology
Tryptases

Substances

Serine Proteinase Inhibitors
Thiazoles
Serine Endopeptidases
chymase 2
Chymases
Tryptases
1,2-benzisothiazoline-3-one