Tryptamine-based human beta3-adrenergic receptor agonists. Part 3: improved oral bioavailability via modification of the sulfonamide moiety.
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.
Sawa
Masaaki
M
Chemistry Research Loboratories, Dainippon Pharmaceutical Co., Ltd, Enoki 33-94, Suita, 564-0053, Japan. masaaki-sawa@dainippon-pharm.co.jp
Mizuno
Kazuhiro
K
Harada
Hiroshi
H
Tateishi
Hirotaka
H
Arai
Yukiyo
Y
Suzuki
Shinya
S
Oue
Mayumi
M
Tsujiuchi
Hiroshi
H
Furutani
Yasuji
Y
Kato
Shiro
S
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
D000322:Adrenergic Agonists; D022702:Receptors, Adrenergic, beta-3; D013449:Sulfonamides; D014363:Tryptamines; C030820:tryptamine