Tryptamine-based human beta3-adrenergic receptor agonists. Part 2: SAR of the methylene derivatives.
A series of tryptamine derivatives with modified sulfonamide were designed, synthesized, and evaluated for their ability to stimulate cAMP accumulation in CHO cells expressing the cloned human beta3-adrenergic receptor (AR). For this series of compounds, our objective was to symmetrize the alpha-position of the tryptamine moiety maintaining its activity and reducing the cost of production. Compound 11h, having m-aminobenzene, exhibited excellent agonistic activity for beta3-AR with excellent subtype selectivity.
Sawa
Masaaki
M
Chemistry Research Laboratories, Dainippon Pharmaceutical Co., Ltd, 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan. masaaki-sawa@dainippon-pharm.co.jp
Tateishi
Hirotaka
H
Mizuno
Kazuhiro
K
Harada
Hiroshi
H
Oue
Mayumi
M
Tsujiuchi
Hiroshi
H
Furutani
Yasuji
Y
Kato
Shiro
S
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006838:Hydrocarbons; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry*; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014363:Tryptamines / Q000737:chemistry*
D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D006838:Hydrocarbons; D013449:Sulfonamides; D014363:Tryptamines; C030011:carbene; D000242:Cyclic AMP; D008697:Methane