Adenosine receptor antagonists: Translating medicinal chemistry and pharmacology into clinical utility

The structure-activity relationship of the ligands synthesized as antagonists for the adenosine receptors (AR) has been analyzed. Recent efforts in medicinal chemistry and pharmacology have yielded substantial number of compounds with selectivity at each AR subtype. In spite of the problem related to ubiquity of adenosine itself in the body and difficulty in devizing adenosine antagonists that affect only one physiological function, nine molecules targeting Ars are now in clinical development. These molecules include the following: A1 ARs, a promising strategy for the treatment of neurological disorders, asthma, and heart and renal failure; A2A antagonists are the most realistic alternatives and support to dopaminergic treatment of Parkinson's disease; A2B is for management of chronic pulmonary diseases, and other molecules are in development as antiasthmatic drugs and also of potential value as antidiabetic, antidiarrheal, antiatherosclerotic, and cardiovascular disorders; and finally, A3 are being considered for application inasthma and chronic obstructive pulmonary diseases, glaucoma, cancer, and stroke.