Tryptamine-based human beta3-adrenergic receptor agonists. Part 1: SAR studies of the 7-position of the indole ring

Kazuhiro Mizuno; Masaaki Sawa; Hiroshi Harada; Hirotaka Tateishi; Mayumi Oue; Hiroshi Tsujiuchi; Yasuji Furutani; Shiro Kato

doi:10.1016/j.bmcl.2004.10.035

Tryptamine-based human beta3-adrenergic receptor agonists. Part 1: SAR studies of the 7-position of the indole ring

Bioorg Med Chem Lett. 2004 Dec 20;14(24):5959-62. doi: 10.1016/j.bmcl.2004.10.035.

Authors

Kazuhiro Mizuno¹, Masaaki Sawa, Hiroshi Harada, Hirotaka Tateishi, Mayumi Oue, Hiroshi Tsujiuchi, Yasuji Furutani, Shiro Kato

Affiliation

¹ Chemistry Research Laboratories, Dainippon Pharmaceutical Co., Ltd, 33-94, Enoki, Suita 564-0053, Japan. kazuhiro-mizuno@dainippon-pharm.co.jp

PMID: 15546707
DOI: 10.1016/j.bmcl.2004.10.035

Abstract

A series of tryptamine-based 2-thiophenesulfonamide derivatives were prepared and their agonistic activity for the beta-adrenergic receptors (ARs) was evaluated. Compound 54, containing 7-methanesulfonyloxy tryptamine, was found to be a highly potent beta3-AR agonist (EC50=0.21 nM, IA=97%) with excellent selectivity for the beta3-AR over the beta1- and beta2-ARs (210- and 86-fold, respectively).

MeSH terms

Adrenergic beta-1 Receptor Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-3 Receptor Agonists*
Adrenergic beta-Agonists / chemical synthesis*
Adrenergic beta-Agonists / chemistry
Drug Evaluation, Preclinical
Humans
Indoles / chemistry*
Molecular Conformation
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Thiophenes / chemical synthesis
Thiophenes / chemistry
Tryptamines / chemistry*

Substances

Adrenergic beta-1 Receptor Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists
Indoles
Sulfonamides
Thiophenes
Tryptamines