Synthesis and SAR development of novel P2X 7 receptor antagonists for the treatment of pain: part 2

S Brumfield, JJ Matasi, D Tulshian, M Czarniecki…

Index: Brumfield, Stephanie; Matasi, Julius J.; Tulshian, Deen; Czarniecki, Michael; Greenlee, William; Garlisi, Charles; Qiu, Hongchen; Devito, Kristine; Chen, Shu-Cheng; Sun, Yongliang; Bertorelli, Rosalia; Ansell, Justin; Geiss, William; Le, Van-Duc; Martin, Gregory S.; Vellekoop, Samuel A.; Haber, James; Allard, Melissa L. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 24 p. 7287 - 7290

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Citation Number: 12

Abstract

Novel P2X7 antagonists were developed using a purine scaffold. These compounds were potent and selective at the P2X7 receptor in human and rodent as well as efficacious in rodent pain models. Compound 15a was identified to have oral potency in several pain models in rodent similar to naproxen, gabapentin and pregabalin. Structure–activity relationship (SAR) development and results of pain models are presented.