New P2X3 receptor antagonists. Part 2: Identification and SAR of quinazolinones

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• 作者：Gá ; bor Szá ; ntó ; Attila Makó ; Istvá ; n Vá ; gó ; Tamá ; s Hergert ; Imre Bata ; Bence Farkas ; Sá ; ndor Kolok ; Mó ; nika Vastag
• 关键词：Purinergic receptor ; ATP ; Ion channel ; P2X3 antagonist ; Chronic cough ; Structure&ndash ; activity relationship ; 4-Oxo-6-aryl-phenethyl-quinazolines ; Nanomolar activity
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 August 2016
• 年：2016
• 卷：26
• 期：16
• 页码：3905-3912
• 全文大小：3513 K

文摘

Numerous potent P2X3 antagonists have been discovered and the therapeutic potential of P2X3 antagonism already comprises proof-of-concept data obtained in clinical trials with the most advanced compound. We have lately reported the discovery and optimization of thia-triaza-tricycle compounds with potent P2X3 antagonistic properties. This Letter describes the SAR of a back-up series containing a 4-oxo-quinazoline central ring. The discovery of the highly potent compounds 51 is presented.