Literature DB >> 24900687

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

Michael A Letavic1, Brian Lord1, Francois Bischoff1, Natalie A Hawryluk1, Serge Pieters1, Jason C Rech1, Zachary Sales1, Adriana I Velter1, Hong Ao1, Pascal Bonaventure1, Victor Contreras1, Xiaohui Jiang1, Kirsten L Morton1, Brian Scott1, Qi Wang1, Alan D Wickenden1, Nicholas I Carruthers1, Anindya Bhattacharya1.   

Abstract

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.

Entities:  

Keywords:  P2X7; depression; neuro-inflammation

Year:  2013        PMID： 24900687      PMCID： PMC4027403          DOI： 10.1021/ml400040v

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  16 in total

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