Synthesis of quinazoline derivatives with acetycholinesterase and butyrylcholinesterase inhibitory activities

Abstract

Quinazolines were the attractive and useful compounds in medicinal chemistry due to their pharmacology activities such as antibacterial, anticancer, antitumor, antidiabetic, anti-inflammatory, analgesic and antiviral activities. In this study, the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of quinazolines derivatives were evaluated. The 4-substitued aminoquinazolines via amination reaction were first synthesized and found that 4-piperidinoquinazolines (12e) possess the highest activity with the IC₅₀ values toward AChE and BChE of 1.3 µM and 7.5 µM, respectively. Then 4-butylaminoquinazolin (12a), 4-piperidinoquinazolines (12e) and 4-morpholinoquinazoline were chosen for further modified their structures by the electron-withdrawing and electron-releasing groups. From the results, there is no activity trend from these groups as substituents on a benzene ring of the core structures of 12a, 12e and 12f. These might be the cause of the different mode of action in each compound. However, this study 4-piperidinoquinazolines (12e) was a candidate for both AChE and BChE inhibitors. 6-Nitro-4-butylaminoquinazoline (16a) was a potent and selective inhibitor toward AChE over BChE while 6,7-dimethoxy-4-butylaminoquinazoline (16d) was a potent and selective inhibitor toward BChE over AChE.