Imidazo-pyrazine derivatives as potent CXCR3 antagonists.
Du X, Gustin DJ, Chen X, Duquette J, McGee LR, Wang Z, Ebsworth K, Henne K, Lemon B, Ma J, Miao S, Sabalan E, Sullivan TJ, Tonn G, Collins TL, Medina JC.
A general way of improving the potency of CXCR3 antagonists with fused hetero-bicyclic cores was identified. Optimization efforts led to the discovery of a series of imidazo-pyrazine derivatives with improved pharmacokinetic properties in addition to increased potency. The efficacy of the lead compound 21 is evaluated in a mouse lung inflammation model.