Design, Synthesis and Biological Evaluation of Novel 2‐Phenylthiazole Derivatives for the Treatment of Alzheimer's Disease

• Published in: ChemistrySelect (Weinheim) 2017-11, Vol.2 (32), p.10572-10579
• Main Authors: Shi, Da‐Hua, Tang, Zong‐ming, Liu, Yu‐Wei, Harjani, Jitendra R., Zhu, Hui‐Long, Ma, Xiao‐Dong, Song, Xiao‐Kai, Liu, Wei‐Wei, Lu, Chen, Yang, Wen‐Tao, Song, Meng‐Qiu
• Format: Article
• Language: English
• Subjects: 2-phenylthiazole; Acetylcholinesterase inhibitor; Alzheimer's disease; butyrylcholinesterase inhibitor; metal-chelating agents
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.201702087

A new series of 2‐phenylthiazole derivatives were designed, synthesized, characterized and evaluated as potential candidates to treat Alzheimer's disease. Most of these compounds exhibited significant acetylcholinesterase inhibitory activities. Among them, compound ethyl 2‐[4‐(4‐{[2‐(pyrrolidin‐1‐yl)ethyl]amino}butoxy)phenyl]thiazole‐4‐carboxylate (5 b–8) exhibited the best acetylcholinesterase inhibition activity with IC50 values of 4.8 μM. Moreover, the compound ethyl 2‐(4‐{[5‐(cyclohexylamino)pentyl]oxy}phenyl)thiazole‐4‐carboxylate (5 c–6) had the best butyrylcholinesterase inhibitory activity, with an IC50 value of 0.16 μM. The docking studies demonstrated that compound 5 b–8 could interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase. Compound 5 b–8 also showed biometal chelating abilities. These attributes highlight 5 b–8 as a promising candidate for further studies directed to the development of novel drugs against Alzheimer's disease. A new series of 2‐phenylthiazole derivatives were designed, synthesized, characterized and evaluated as potential candidates to treat Alzheimer's disease. Among them, compound ethyl 2‐[4‐(4‐{[2‐(pyrrolidin‐1‐yl)ethyl]amino}butoxy)phenyl]thiazole‐4‐carboxylate (5 b–8) exhibited the best acetylcholinesterase inhibition activity with IC50 values of 4.8 μM and biometal chelating abilities. These attributes highlight 5 b–8 as a promising candidate for further studies directed to the development of novel drugs against Alzheimer's disease.