Novel 8-heterocyclyl xanthine derivatives in drug development - an update

Naturally occurring methyl xanthines, especially caffeine and theophylline, have been widely investigated for their pharmacological properties as cognition enhancers, bronchodilator agents and mild diuretics. The xanthine core (3,7-dihydro-1H-purine-2,6-dione) has been largely manipulated in the search for selective ligands for different pharmacological targets, proving to be a versatile scaffold for the development of lead compounds in multiple therapeutic areas. The introduction of a heterocycle at the 8-position of some xanthine derivatives demonstrated to be a successful strategy for the identification of potent and selective A(1) or A(2B) adenosine receptors antagonists as potential agents for the treatment of Alzheimer's disease and asthma, respectively. Interesting examples of 8-heterocyclyl-xanthines as dipeptidyl peptidase IV inhibitors and liver X receptor agonists have been claimed for their possible therapeutic use in the treatment of Type 2 diabetes and atherosclerosis.