کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1363689 | 981520 | 2009 | 5 صفحه PDF | دانلود رایگان |
A range of heterocycle fused azepines were synthesized in order to find a CNS penetrant, selective 5-HT2C agonist for the treatment of incontinence. The pyridazo-azepines such as compound 11 were shown to be potent 5-HT2C agonists and have potential for CNS penetration and good in vitro ADME properties but lacked selectivity against 5-HT2B. Fusing a further heterocycle gave the selective triazolopyrimido-azepines. An example of this series, compound 36, was shown to be potent, selective, metabolically stable in vitro and efficacious in an in vivo model of stress urinary incontinence.
Fused azepines such as compound 11 were shown to be potent 5-HT2C agonists with the potential for CNS penetration and good in vitro ADME properties. Improved selectivity against the 5-HT2B receptor was achieved with tricyclic analogues such as compound 36.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 19, Issue 17, 1 September 2009, Pages 4999–5003