Piperazinebenzylamines as potent and selective antagonists of the human melanocortin-4 receptor

[Display omitted] SAR studies of a series of piperazinebenzylamines resulted in the discovery of potent antagonists of the human melanocortin-4 receptor. Compounds 11c, 11d, and 11l, which had K i values of 21, 14, and 15 nM, respectively, possessed low efficacy in cAMP stimulation (∼15% of α-MSH ma...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2004-11, Vol.14 (22), p.5605-5609
Hauptverfasser:	Pontillo, Joseph, Tran, Joseph A., Fleck, Beth A., Marinkovic, Dragan, Arellano, Melissa, Tucci, Fabio C., Lanier, Marion, Nelson, Jodie, Parker, Jessica, Saunders, John, Murphy, Brian, Foster, Alan C., Chen, Chen
Format:	Artikel
Sprache:	eng
Schlagworte:	Antagonist Benzylamines - chemical synthesis Benzylamines - pharmacology Biological and medical sciences Humans MC4 Medical sciences Melanocortin Miscellaneous Molecular Structure Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems Pharmacology. Drug treatments Piperazinebenzylamine Piperazines - chemical synthesis Piperazines - pharmacology Receptor, Melanocortin, Type 4 - antagonists & inhibitors Structure-Activity Relationship
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Zusammenfassung:	[Display omitted] SAR studies of a series of piperazinebenzylamines resulted in the discovery of potent antagonists of the human melanocortin-4 receptor. Compounds 11c, 11d, and 11l, which had K i values of 21, 14, and 15 nM, respectively, possessed low efficacy in cAMP stimulation (∼15% of α-MSH maximal level) mediated by MC4R, and functioned as antagonists in inhibition of α-MSH-stimulated cAMP release in a dose-dependent manner ( 11l, IC 50 = 36 nM).
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2004.08.055