Tryptamine-based human beta3-adrenergic receptor agonists. Part 3: improved oral bioavailability via modification of the sulfonamide moiety

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

doi:10.1016/j.bmcl.2004.12.033

Tryptamine-based human beta3-adrenergic receptor agonists. Part 3: improved oral bioavailability via modification of the sulfonamide moiety

Bioorg Med Chem Lett. 2005 Feb 15;15(4):1061-4. doi: 10.1016/j.bmcl.2004.12.033.

Authors

Masaaki Sawa¹, Kazuhiro Mizuno, Hiroshi Harada, Hirotaka Tateishi, Yukiyo Arai, Shinya Suzuki, Mayumi Oue, Hiroshi Tsujiuchi, Yasuji Furutani, Shiro Kato

Affiliation

¹ Chemistry Research Loboratories, Dainippon Pharmaceutical Co., Ltd, Enoki 33-94, Suita, 564-0053, Japan. masaaki-sawa@dainippon-pharm.co.jp

PMID: 15686912
DOI: 10.1016/j.bmcl.2004.12.033

Abstract

The continued SAR investigation of tryptamine-based human beta(3)-adrenergic receptor (AR) agonists is reported. Prior efforts resulted in the identification of 2 as a potent beta(3)-AR agonist. Further modification of the left side arylsulfonamide portion in 2 provided compounds with good cell permeability, which have potent agonistic activity for beta(3)-AR. Cinnamylamine analog 16i exhibited an excellent agonistic profile in vitro and good oral bioavailability in rats.

MeSH terms

Administration, Oral
Adrenergic Agonists / chemical synthesis*
Adrenergic Agonists / pharmacokinetics*
Adrenergic Agonists / pharmacology
Biological Availability
Cell Membrane Permeability
Humans
Inhibitory Concentration 50
Receptors, Adrenergic, beta-3 / metabolism*
Structure-Activity Relationship
Sulfonamides / chemical synthesis*
Sulfonamides / pharmacokinetics
Sulfonamides / pharmacology
Tryptamines*

Substances

Adrenergic Agonists
Receptors, Adrenergic, beta-3
Sulfonamides
Tryptamines
tryptamine