Synthesis and Pharmacological Characterization of Two Novel, Brain Penetrating P2X7 Antagonists

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• 作者：Michael A. Letavic ; Brian Lord ; Francois Bischoff ; Natalie A. Hawryluk ; Serge Pieters ; Jason C. Rech ; Zachary Sales ; Adriana I. Velter ; Hong Ao ; Pascal Bonaventure ; Victor Contreras ; Xiaohui Jiang ; Kirsten L. Morton ; Brian Scott ; Qi Wang ; Alan D. Wickenden ; Nicholas I. Carruthers ; Anindya Bhattacharya
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：April 11, 2013
• 年：2013
• 卷：4
• 期：4
• 页码：419-422
• 全文大小：298K
• 年卷期：v.4,no.4(April 11, 2013)
• ISSN：1948-5875

文摘

The synthesis and preclinical characterization of two novel, brain penetrating P2X₇ compounds will be described. Both compounds are shown to be high potency P2X₇ antagonists in human, rat, and mouse cell lines and both were shown to have high brain concentrations and robust receptor occupancy in rat. Compound 7 is of particular interest as a probe compound for the preclinical assessment of P2X₇ blockade in animal models of neuro-inflammation.

Keywords:

P2X₇; neuro-inflammation; depression