Novel and potent 3-(2,3-dichlorophenyl)-4-(benzyl)-4H-1,2,4-triazole P2X7 antagonists.
Structure-activity relationship (SAR) studies were conducted around early tetrazole-based leads 3 and 4. Replacements for the tetrazole core were investigated and the pendant benzyl substitution was reoptimized with a triazole isostere. Triazole-based P2X(7) antagonists were identified with similar potency to the lead compound 4 but with improved physiochemical properties. Compound 12 was active in a rat model of neuropathic pain.
Carroll
William A
WA
Abbott Laboratories, Neuroscience Research, 100 Abbott Park Road, Abbott Park, IL 60064, USA. william.a.carroll@abbott.com
Kalvin
Douglas M
DM
Perez Medrano
Arturo
A
Florjancic
Alan S
AS
Wang
Ying
Y
Donnelly-Roberts
Diana L
DL
Namovic
Marian T
MT
Grayson
George
G
Honoré
Prisca
P
Jarvis
Michael F
MF
D000818:Animals; D058919:Purinergic P2 Receptor Antagonists; D051381:Rats; D058486:Receptors, Purinergic P2X7; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology*
C546470:P2rx7 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D058486:Receptors, Purinergic P2X7; D014230:Triazoles