Structure-activity relationship of benzo[b]thiophene-2-sulfonamide derivatives as novel human chymase inhibitors

Hidekazu Masaki; Yusuke Mizuno; Akira Tatui; Akira Murakami; Yuuki Koide; Shoji Satoh; Atsuo Takahashi

doi:10.1016/j.bmcl.2003.08.040

Structure-activity relationship of benzo[b]thiophene-2-sulfonamide derivatives as novel human chymase inhibitors

Bioorg Med Chem Lett. 2003 Nov 17;13(22):4085-8. doi: 10.1016/j.bmcl.2003.08.040.

Authors

Hidekazu Masaki¹, Yusuke Mizuno, Akira Tatui, Akira Murakami, Yuuki Koide, Shoji Satoh, Atsuo Takahashi

Affiliation

¹ Drug Research Department, Tokyo Research Laboratories, Toa Eiyo Ltd., 2-293-3 Amanuma-cho, Omiya-ku, Saitama-shi, Saitama 330-0834, Japan. hidekazu.masaki@toaeiyo.co.jp

PMID: 14592513
DOI: 10.1016/j.bmcl.2003.08.040

Abstract

We have identified a new class of chymase inhibitor through a substituent analysis of MWP00965, which we previously discovered by in silico screening. TY-51076 (7) showed high potency (IC(50)=56 nM) and excellent selectivity for chymase compared to chymotrypsin and cathepsin G (>400-fold). The synthesis and structure-activity relationship of this class are described.

MeSH terms

Chymases
Drug Design
Humans
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / pharmacology*
Serine Endopeptidases / drug effects
Serine Endopeptidases / metabolism*
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / pharmacology*
Thiophenes / chemical synthesis
Thiophenes / pharmacology

Substances

Protease Inhibitors
Sulfonamides
Thiophenes
benzothiophene
Serine Endopeptidases
Chymases