Exploration of Novel Ureidobenzothiazole Library Against Neuroinflammation

Abstract

Combinatorial chemistry serves as a powerful tool in lead discovery and lead optimization by facilitating the rapid generation of potential candidates for screening. Lead optimization involves structural modifications of a hit compound to a lead compound that has demonstrated the desired biological or pharmacological activities, often in an in-vitro assay system. Among the broad range of templates, heterocyclic scaffolds represent the most promising molecules as leading structures for the discovery of novel synthetic drugs. In particular, the 2-aminothiazole core is found in numerous drugs and clinical and preclinical candidates that address a broad spectrum of targets.1 For example, the 2-aminothiazole compounds bind to enzymes such as cyclooxygenases, 2 phosphodiesterases,3 kinases4 and acetylcholinesterase 5 and thereby attach to receptors such as integrins and various members of the GPCR family. Recently, the 2- aminothiazole-bearing compounds were reported as a new class of small molecules with antiprion activity in prioninfected neuroblastoma cell lines,6 and as lead compounds multitargeted against Alzheimer disease and anticholinesterase as a single chemical entity in a more balanced biological profile.