Synthesis and structure-activity relationships of tri-substituted thiazoles as RAGE antagonists for the treatment of Alzheimer's disease.

A series of thiazole derivatives were designed, and prepared to develop RAGE antagonist for the treatment of Alzheimer's disease (AD). SAR studies were performed to optimize inhibitory activity on Aß-RAGE binding. SAR studies showed that introducing an amino group at part A was essential for inhibitory activity on Aß-RAGE binding. Compounds selected from Aß-RAGE binding screening displayed inhibitory activity on Aß transport across BBB. They also showed inhibitory activity against Aß-induced NF-κB activation. These results indicated that our derivatives had a potential as therapeutic agent for the treatment of AD.