1,721,113 research outputs found
Novel beta3 adrenergic receptor ligands: a patent review
No full textINTRODUCTION: 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. 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 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. EXPERT OPINION: 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
Heterocycles and their radiolabeled analogs useful as COX-1 selective inhibitors
No full textThe present invention relates to novel heterocycles which are potent and selective inhibitors of cyclooxygenase-1 (COX-1) and to their radiolabeled derivatives thereof which are both useful as theranostics of a number of pathologies
Novel pyrazoles and their radiolabeled derivatives useful as COX-1 selective inhibitors
No full textThe present invention relates to novel pyrazoles which are potent and selective inhibitors of cyclooxygenase-1 (COX-1) and to their radiolabeled derivatives thereof which are both useful as theranostics of a number of pathologies
Update on SAR studies toward new COX-1 selective inhibitors
No full textFew selective cyclooxygenase-1 (COX-1) inhibitors have been described up to now, although recent studies underlined the involvement of COX-1 in the carcinogenesis, pathogenesis of neuroinflammation, cardiovascular diseases and pain. Among the known COX-1 inhibitors none proved to be a good drug candidate, with the exception of mofezolac, that is clinically used as an analgesic drug. New selective inhibitors were very often discovered as a minor achievement during SAR investigations to discover selective COX-2 inhibitors (COXIBs). After a recognition of the new COX-1 inhibitors synthesized in the last five years, it was attempted to draw, for each chemical class, a structure which might highlight the determinant molecular features able to switch the selectivity towards the COX-1 isoform. Overall, this review could constitute a tool to a better design of novel selective COX-1 inhibitors, to be used in a disease theranostic approach targeting COX-1
Selective COX-1 inhibition: a therapeutic target to be reconsidered
No full textSince cyclooxygenase (COX) isozymes discovery, many papers and reviews have been published to describe the structural bases of COX inhibition, and to debate on the therapeutic and adverse effects of worldwide clinically used nonsteroidal anti-inflammatory drugs (NSAIDs), included COX-2 selective inhibitors (well known as Coxibs). COX-2 inhibition has been widely investigated, whereas the role of COX-1 in human pathophysiology is mostly not yet well ascertained. As time goes on, the cliché that the constitutively expressed isoform COX-1 is only involved in normal physiological functions, such as platelet aggregation, gastric mucosa protection and renal electrolyte homeostasis is going to be shattered. Low-dose aspirin, behaving as a preferential inhibitor of platelet COX-1, allowed to enlighten the role exerted by this isoenzyme in many mammalian cell types. This review would elucidate the most recent findings on selective COX-1 inhibition and their relevance to human pathology such as cancer, neuro-inflammation, cardioprotection, fever and pain. It would also focus on the design and development of new highly selective COX-1 inhibitors, useful tools in pharmacological studies aimed at gaining a deeper insight of the role of COX-1 in human health and disease. Among the traditional NSAIDs, other then aspirin and indomethacin, only few examples of selective COX-1 inhibitors (SC-560, FR122047, mofezolac, P6 and TFAP) have been so far identified. This review has also the scope to stimulate the development of novel drugs, which activity is COX-1 mediated
Receptor drug interaction: europium employment for studying the biochemical pathway of GPRC activation
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