Design and synthesis of pyridazinone-based 5-HT(2C) agonists

The SAR of a series of pyridazinone derived 5-HT(2C) agonists has been explored and resulted in identification of a compound with excellent levels of 5-HT(2C) functional agonism and selectivity over 5-HT(2A) and 5-HT(2B). This compound displayed good in vivo efficacy in pre-clinical models of stress...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009-10, Vol.19 (19), p.5791-5795
Hauptverfasser:	Allerton, Charlotte M N, Andrews, Mark D, Blagg, Julian, Ellis, David, Evrard, Edel, Green, Martin P, Liu, Kevin K-C, McMurray, Gordon, Ralph, Michael, Sanderson, Vivienne, Ward, Robin, Watson, Lesa
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Dogs Drug Design Humans Piperazines - chemical synthesis Piperazines - chemistry Piperazines - pharmacology Pyridazines - chemical synthesis Pyridazines - chemistry Pyridazines - pharmacokinetics Pyridazines - pharmacology Receptor, Serotonin, 5-HT2A - metabolism Receptor, Serotonin, 5-HT2B - metabolism Receptor, Serotonin, 5-HT2C - metabolism Serotonin 5-HT2 Receptor Agonists Serotonin Receptor Agonists - chemical synthesis Serotonin Receptor Agonists - chemistry Serotonin Receptor Agonists - pharmacokinetics Structure-Activity Relationship Urinary Incontinence, Stress - drug therapy
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Zusammenfassung:	The SAR of a series of pyridazinone derived 5-HT(2C) agonists has been explored and resulted in identification of a compound with excellent levels of 5-HT(2C) functional agonism and selectivity over 5-HT(2A) and 5-HT(2B). This compound displayed good in vivo efficacy in pre-clinical models of stress urinary incontinence, despite having physiochemical properties commensurate with impaired CNS penetration.
ISSN:	1464-3405
DOI:	10.1016/j.bmcl.2009.07.136