β₃-Adrenoceptor ligand development history through patent review

Abstract

Introduction: Stimulation of the β₃-adrenoceptor (β₃-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 β₃-AR is recognized as an attractive target for drug discovery. Simultaneous activation of the β₁- and β₂-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 β₃-AR agonists through original synthetic chemistry, extensive in vitro tests and detailed preclinical investigations to various phases of clinical trials.

Areas covered: 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 β₃-AR through to June 2010. This review discusses the enormous efforts made by private and public research laboratories to uncover β₃-AR ligands and to prove their usefulness as drugs.

Expert opinion: Remarkable knowledge has been gained about the physio-pathological role of the β₃-AR to date. Many highly potent and selective β₃-AR ligands (agonists, antagonists and inverse agonists) have been discovered; however, further investigations are still needed to identify novel compounds acting as β₃-AR ligands in order to adequately treat the diseases in which β₃-AR is involved.

Keywords::

• anxiety and depression
• apoptosis
• arylethanolamine
• aryloxypropanolamine
• cachexia
• colon cancer
• heart failure
• intestine disorders
• metabolic syndrome
• obesity and type 2 diabetes
• overactive bladder
• preterm labor
• structure–activity relationship
• β₃-adrenoceptor

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