title: β(3)-Adrenoceptor ligand development history through patent review.
abstract: BACKGROUND
  Stimulation of the β(3)-adrenoceptor (β(3)-AR) is thought to be a valuable approach for the treatment of obesity, type 2 diabetes, heart failure, frequent urination, preterm labor, anxiety and depression. Therefore, the β(3)-AR is recognized as an attractive target for drug discovery. Simultaneous activation of the β(1)- and β(2)-AR can cause undesirable side effects such as increased heart rate and muscle tremors. Consequently, much effort has been directed towards the design and development of selective β(3)-AR agonists through original synthetic chemistry, extensive in vitro tests and detailed preclinical investigations to various phases of clinical trials.
  
  
  METHODS
  SciFinder Scholar, PubMed, ISI web of Knowledge(SM), Espacenet, ClinicalTrials and Google have been used as the main sources for retrieving literature and patents filed since the discovery of β(3)-AR through to June 2010. This review discusses the enormous efforts made by private and public research laboratories to uncover β(3)-AR ligands and to prove their usefulness as drugs.
  
  
  CONCLUSIONS
  Remarkable knowledge has been gained about the physio-pathological role of the β(3)-AR to date. Many highly potent and selective β(3)-AR ligands (agonists, antagonists and inverse agonists) have been discovered; however, further investigations are still needed to identify novel compounds acting as β(3)-AR ligands in order to adequately treat the diseases in which β(3)-AR is involved.
authors.affiliation: Dipartimento Farmaco-Chimico, University of Bari, Via E Orabona 4, 70125 Bari, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Perrone
authors.forename: Antonio
authors.initials: A
authors.lastname: Scilimati
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000627:therapeutic use*; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003863:Depression / Q000188:drug therapy; D005317:Fetal Growth Retardation / Q000188:drug therapy; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006975:Hypertension, Portal / Q000188:drug therapy; D007410:Intestinal Diseases / Q000188:drug therapy; D008024:Ligands; D010330:Patents as Topic; D022702:Receptors, Adrenergic, beta-3 / Q000737:chemistry / Q000502:physiology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D008024:Ligands; D022702:Receptors, Adrenergic, beta-3