title: Tryptamine-based human beta3-adrenergic receptor agonists. Part 3: improved oral bioavailability via modification of the sulfonamide moiety.
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.
authors.affiliation: Chemistry Research Loboratories, Dainippon Pharmaceutical Co., Ltd, Enoki 33-94, Suita, 564-0053, Japan. masaaki-sawa@dainippon-pharm.co.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizuno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Harada
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Tateishi
authors.forename: Yukiyo
authors.initials: Y
authors.lastname: Arai
authors.forename: Shinya
authors.initials: S
authors.lastname: Suzuki
authors.forename: Mayumi
authors.initials: M
authors.lastname: Oue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsujiuchi
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Furutani
authors.forename: Shiro
authors.initials: S
authors.lastname: Kato
mesh_terms: D000284:Administration, Oral; D000322:Adrenergic Agonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D002463:Cell Membrane Permeability; D006801:Humans; D020128:Inhibitory Concentration 50; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D014363:Tryptamines
chemical_list: D000322:Adrenergic Agonists; D022702:Receptors, Adrenergic, beta-3; D013449:Sulfonamides; D014363:Tryptamines; C030820:tryptamine