Tryptamine-based human beta3-adrenergic receptor agonists. Part 1: SAR studies of the 7-position of the indole ring.
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).
Mizuno
Kazuhiro
K
Chemistry Research Laboratories, Dainippon Pharmaceutical Co., Ltd, 33-94, Enoki, Suita 564-0053, Japan. kazuhiro-mizuno@dainippon-pharm.co.jp
Sawa
Masaaki
M
Harada
Hiroshi
H
Tateishi
Hirotaka
H
Oue
Mayumi
M
Tsujiuchi
Hiroshi
H
Furutani
Yasuji
Y
Kato
Shiro
S
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry; D014363:Tryptamines / Q000737:chemistry*
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D007211:Indoles; D013449:Sulfonamides; D013876:Thiophenes; D014363:Tryptamines