Synthesis, biological evaluation and molecular modeling of 1-oxa-4-thiaspiro- and 1,4-dithiaspiro[4.5]decane derivatives as potent and selective 5-HT_1A receptor agonists

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• 作者：Silvia Franchini^a ; Leda Ivanova Manasieva^a ; Claudia Sorbi^a ; Umberto M. Battisti^a ; Paola Fossa^b ; Elena Cichero^b ; Nunzio Denora^c ; Rosa Maria Iacobazzi^c ; ^d ; Antonio Cilia^e ; Lorenza Pirona^e ; Simone Ronsisvalle^f ; Giuseppina Aricò ; ^f ; Livio Brasili^a ; ^{livio.brasili@unimore.it}
• 关键词：5-HT1A receptor ; Agonist ; Neuroprotection ; BBB penetration ; Analgesic activity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：125
• 期：Complete
• 页码：435-452
• 全文大小：4352 K
• 卷排序：125

文摘

1,4-dioxaspiro[4,5]dec-2-ylmethyl-amines were synthesized and tested. Oxygen/Sulphur substitution favors 5-HT1AR affinity, potency and efficacy. 14 and 15 behave as selective and potent 5-HT1AR partial agonists. 15 shows a promising neuroprotective activity in-vitro. 15 reduces significantly the linking time in Phase II at a dose of 10 mg/kg i.p.