β(3)-Adrenoceptor ligand development history through patent review

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.

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.

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.