Discovery of heteroaryl sulfonamides as new EP1 receptor selective antagonists

Atsushi Naganawa; Toshiaki Matsui; Tetsuji Saito; Masaki Ima; Tadashi Tatsumi; Shingo Yamamoto; Masayuki Murota; Hiroshi Yamamoto; Takayuki Maruyama; Shuichi Ohuchida; Hisao Nakai; Kigen Kondo; Masaaki Toda

doi:10.1016/j.bmc.2006.05.076

Discovery of heteroaryl sulfonamides as new EP1 receptor selective antagonists

Bioorg Med Chem. 2006 Oct 1;14(19):6628-39. doi: 10.1016/j.bmc.2006.05.076. Epub 2006 Jun 19.

Authors

Atsushi Naganawa¹, Toshiaki Matsui, Tetsuji Saito, Masaki Ima, Tadashi Tatsumi, Shingo Yamamoto, Masayuki Murota, Hiroshi Yamamoto, Takayuki Maruyama, Shuichi Ohuchida, Hisao Nakai, Kigen Kondo, Masaaki Toda

Affiliation

¹ Minase Research Institute, Ono Pharmaceutical Co., Ltd, Shimamoto, Mishima, Osaka 618-8585, Japan. naganawa@ono.co.jp

PMID: 16784865
DOI: 10.1016/j.bmc.2006.05.076

Abstract

4-({2-[Isobutyl(phenylsulfonyl)amino]-5-(trifluoromethyl)phenoxy}methyl)benzoic acid (1) is a functional PGE2 antagonist selective for EP1 receptor subtype. Analogs of 1, in which the phenyl-sulfonyl moiety has been replaced with more hydrophilic heteroarylsulfonyl moieties, exhibited more optimized antagonist activity, while some of them showed in vivo antagonist activity. Structure-activity relationship (SAR) studies are also presented.

MeSH terms

Alprostadil / metabolism*
Animals
CHO Cells
Chromatography, Thin Layer
Cricetinae
Dinoprostone / analogs & derivatives
Dinoprostone / metabolism
Dinoprostone / pharmacology
Drug Design
Female
Humans
Indicators and Reagents
Oxidation-Reduction
Rats
Receptors, Prostaglandin E / antagonists & inhibitors*
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / pharmacology*
Urinary Bladder / drug effects

Substances

Indicators and Reagents
Receptors, Prostaglandin E
Sulfonamides
sulprostone
Alprostadil
Dinoprostone