Development of Caffeine Derivatives as Novel Adenosine Receptor Antagonist

The P1 adenosine receptors are a class of purinergic G protein-coupled receptors with adenosine as endogenous ligand. There are four subtypes of adenosine receptors; A1, A2A, A2B, and A3. Adenosine A2A receptors (A2AR) are found in high density in certain brain regions, such as striatum, nucleus accumbens, and olfactory tubercle. Therefore antagonists at the A2AR have been proposed as novel therapeutics for neurodegenerative diseases, e.g. Parkinson?s disease (PD) and Alzheimer?s disease (AD). Adenosine A2A receptor antagonist may also be active as cognition enhancers, neuroprotective, anti-depressive, and analgesic drugs. Novel xanthine derivatives will be designed, synthesized and characterized applying a wide range of physicochemical techniques. The novel compounds are expected to antagonize the A2AR with high affinity and selectivity and furthermore exhibit suitable pharmacokinetic properties.