The scientists and consultants at Discovery Therapeutics, Inc. have invented and characterized a number of molecules that are selective antagonists at adenosine A1 receptors. Preclinical studies reveal N-086l and WRC-0571 to be potent, competitive antagonists, highly specific for adenosine receptors, and at least 100 fold selective for the A1 receptor subtype. Safety and toxicology studies suggest that N-0861 has a therapeutics ratio in excess of 100. Clinical studies conducted with N- 0861 documented the selectivity and potency of this molecule in humans, and thus validated the more predictive animal models. These studies provided important new information on human adenosine pharmacology. but also demonstrated that the modest potency and poor solubility of N-0861 in an irritating acid vehicle limited its potential as a marketable therapeutic. By following the successful approach used to develop N-0861, we propose to advance the superior backup molecule. WRC-0571, from preclinical status to Phase Il clinical trials using SBIR support. The Phase I SBIR proposal is designed to test WRC-057l in an animal model of cardiopulmonary resuscitation and prepare for GMP synthesis and formulation. If successful, a Phase II SBIR application will be submitted to support manufacture of clinical trials supplies, toxicology, and Phase I and Il clinical trials.Proposed commercial application:The prognosis for survival following cardiac arrest is very poor. pharmacological interventions that can improve the effectiveness of cardiopulmonary resuscitation would be of great benefit. Because of the large number of CPR procedures performed each year, a pharmacological aid to CPR would be of great commercial potential.National Institute of Heart, Lung, and Blood Institute (NHLBI)
