Barbituric Acid Derivatives as Protein Tyrosine Phosphatase Inhibitors

摘要

Barbiturates infer derivatives of barbituric acid. Commonly used barbiturates like phenobarbital and secobarbital have subs-tituents at the 5 position on this basic skeleton. Barbiturates slow down central nervous system (CNS) functions and have been used to treat medical conditions such as epileptic seizures and as anesthesia for surgical procedures. Beside the effects as CNS depressants, barbiturates have been shown to exhibit wide variety of other biological activities, including anti-tumor activities, immuno-modulating activities, herbicidal or insect-icidal activities, PPARy agonistic activities, and inhibitory activities against mucosal addressin cell adhesion molecule-1 interactions. " Notably, barbiturates, including phenobarbital and secobarbital, were also found to inhibit the phosphatase activity of calcineurin, a protein Ser/Thr phosphatase. In view of this observation, we considered the barbituric acid moiety as a candidate scaffold for the design of protein tyrosine phosphatase (PTP) inhibitors.