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

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.

SUBMITTER: Letavic MA

PROVIDER: S-EPMC4027403 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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

Letavic Michael A MA Lord Brian B Bischoff Francois F Hawryluk Natalie A NA Pieters Serge S Rech Jason C JC Sales Zachary Z Velter Adriana I AI Ao Hong H Bonaventure Pascal P Contreras Victor V Jiang Xiaohui X Morton Kirsten L KL Scott Brian B Wang Qi Q Wickenden Alan D AD Carruthers Nicholas I NI Bhattacharya Anindya A

ACS medicinal chemistry letters 20130312 4

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. ...[more]

PMID: 24900687

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