title: Recent developments in the design of orally bioavailable beta3-adrenergic receptor agonists.
abstract: The beta3-adrenergic receptor (beta3-AR) has been shown to mediate various pharmacological and physiological effects such as lipolysis, thermogenesis, and relaxation of the urinary bladder. Activation of the beta3-AR is thought to be a possible approach for the treatment of obesity, type 2 diabetes mellitus, and frequent urination. Therefore, the beta3-AR is recognized as an attractive target for drug discovery. On the other hand, activation of the beta1- or beta2-AR can cause undesirable side effects such as increased heart rate or muscle tremors. Consequently, a number of recent efforts in this field have been directed toward the design of selective agonists for the beta3-AR. This review summarizes recent advances in beta3-AR agonists with an emphasis on recent attempts to create potent, selective and orally bioavailable small-molecule agonists.
authors.affiliation: Chemistry Research Laboratories, Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd., 33-94 Enoki-cho, Suita, Osaka 564-0053, Japan. masaaki-sawa@ds-pharma.co.jp
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Harada
mesh_terms: D000284:Administration, Oral; D000322:Adrenergic Agonists / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D058667:Adrenergic beta-3 Receptor Agonists; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D001682:Biological Availability; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D015195:Drug Design; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000322:Adrenergic Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D019440:Anti-Obesity Agents