Species-Independent A3 Adenosine Receptor Agonists Which May Be Useful for Treating Ischemia, Controlling Inflammation, and Regulating Cell Proliferation

This invention claims species-independent agonists of A₃AR, specifically (N)-methanocarba adenine nucleosides and pharmaceutical compositions comprising such nucleosides. The A₃ adenosine receptor (A₃AR) subtype has been linked with helping protect the heart from ischemia, controlling inflammation, and regulating cell proliferation. Agonists of the human A₃AR subtype have been developed that are also selective for the mouse A₃AR while retaining selectivity for the human receptor. This solves a problem for clinical development because animal model testing is important for pre-clinical validation of drug function. Novel agonists have been made that exhibit as much as 6000x selectivity for A₃ versus A₁ in humans while retaining at least 400x selectivity for A₃ versus A₁ in mice. In addition, the molecules of the invention exhibit very low nanomolar affinity. This innovation will not only facilitate moving A₃ agonists into the clinical phase of drug development by being more amenable to animal studies, but also provide much greater selectivity in humans, and thereby potentially fewer side effects than drugs currently undergoing clinical trials.