Aryl sulphonyl amides as potent agonists of the growth hormone secretagogue (ghrelin) receptor
Department of Medicinal Chemistry & DMPK, Neurology & GI Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.Bioorganic & medicinal chemistry letters (Impact Factor: 2.33). 02/2009; 19(3):684-7. DOI: 10.1016/j.bmcl.2008.12.042
ABSTRACT As part of an on-going lead optimisation effort, a cross screening exercise identified an aryl sulphonyl amide hit that was optimised to afford a highly potent series of ghrelin receptor agonists.
Annual reports in medicinal chemistry 01/2011; 46:135-154. DOI:10.1016/B978-0-12-386009-5.00018-7 · 1.19 Impact Factor
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ABSTRACT: Ghrelin is a unique bioactive peptide with respect to both the structure and its biological function. This 28-amino acid peptide is modified with an n-octanoyl group at serine-3, and accordingly is the only lipidated biologically active peptide hormone known so far. Ghrelin binds to the so-called ghrelin or GHS receptor, a member of the class A of G-protein coupled receptors, which leads to Ca(2+) release intracellularly due to the activation of the Gq-system. Interestingly, the ghrelin receptor shows a significant constitutive activity which means that in addition to agonists and antagonists, inverse agonists play an important role in receptor modulation. In this review, the major activities of ghrelin are summarized with a strong focus on the regulation of food intake. So far reported agonists, antagonists and inverse agonists are shown and structure activitiy relationships are discussed. Furthermore, the application of ghrelin ligands as novel anti-obesity drugs is outlined and the state of the art in this field is summarized.Journal of Peptide Science 11/2009; 15(11):711-30. DOI:10.1002/psc.1177 · 1.86 Impact Factor
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