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

Naturally occurring Me xanthines, esp. caffeine and theophylline, have been widely investigated for their pharmacol. 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 pharmacol. targets, proving to be a versatile scaffold for the development of lead compds. in multiple therapeutic areas. The introduction of a heterocycle at the 8-position of some xanthine derivs. demonstrated to be a successful strategy for the identification of potent and selective A1 or A2B adenosine receptors antagonists as potential agents for the treatment of Alzheimer's disease and asthma, resp. 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.