Thienyl and phenyl alpha-halomethyl ketones: new inhibitors of glycogen synthase kinase (GSK-3beta) from a library of compound searching.

Glycogen synthase kinase (GSK-3beta) plays a crucial role in Alzheimer's disease (AD). Its inhibition is a valid approach to the treatment of AD. In this initial letter, some thienyl and phenyl alpha-halomethyl ketones are described as new non-ATP competitive inhibitors of GSK-3beta. They are considered as lead compounds for designing and synthesizing new series, to carry out SAR studies, clear up the mechanism of action, and, in general, evaluate their therapeutical usefulness.