title: Tryptamine-based human beta3-adrenergic receptor agonists. Part 2: SAR of the methylene derivatives.
abstract: 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.
authors.affiliation: Chemistry Research Laboratories, Dainippon Pharmaceutical Co., Ltd, 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan. masaaki-sawa@dainippon-pharm.co.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sawa
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Tateishi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizuno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Harada
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: 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*
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D000318:Adrenergic beta-Agonists; D006838:Hydrocarbons; D013449:Sulfonamides; D014363:Tryptamines; C030011:carbene; D000242:Cyclic AMP; D008697:Methane