title: 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.
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Letavic
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Lord
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Francois
authors.initials: F
authors.lastname: Bischoff
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Hawryluk
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Serge
authors.initials: S
authors.lastname: Pieters
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Rech
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Sales
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Adriana I
authors.initials: AI
authors.lastname: Velter
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Ao
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Pascal
authors.initials: P
authors.lastname: Bonaventure
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Victor
authors.initials: V
authors.lastname: Contreras
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: Morton
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Scott
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Wickenden
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Carruthers
authors.affiliation: Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.
authors.forename: Anindya
authors.initials: A
authors.lastname: Bhattacharya
keywords: P2X7; depression; neuro-inflammation