The SAR development of substituted purine derivatives as selective CB2 agonists for the treatment of chronic pain.

ABSTRACT

Osteoarthritis (OA) and the associated joint pain are highly prevalent and a leading cause of disability. We have previously reported the identification of a series of purines as selective CB2 agonists and the identification of compound 1 as a clinical candidate for the treatment of joint pain. In this article we describe the further SAR development of the purine scaffold leading to the discovery of compound 6 as a potent, CNS penetrating CB2 agonist with high selectivity for CB2 over CB1 and oral efficacy in animal models of chronic OA pain.