126848-89-3Relevant academic research and scientific papers
Synthesis and pharmacological evaluation of donepezil-based agents as new cholinesterase/monoamine oxidase inhibitors for the potential application against Alzheimer’s disease
Li, Fan,Wang, Zhi-Min,Wu, Jia-Jia,Wang, Jin,Xie, Sai-Sai,Lan, Jin-Shuai,Xu, Wei,Kong, Ling-Yi,Wang, Xiao-Bing
, p. 41 - 53 (2016/12/16)
In a continuing effort to develop multitargeted compounds as potential treatment agents against Alzheimer's disease (AD), a series of donepezil-like compounds were designed, synthesized and evaluated. In vitro studies showed that most of the designed compounds displayed potent inhibitory activities toward AChE, BuChE, MAO-B and MAO-A. Among them, w18 was a promising agent with balanced activities, which exhibited a moderate cholinesterase inhibition (IC50, 0.220 μM for eeAChE; 1.23 μM for eqBuChE; 0.454 μM for hAChE) and an acceptable inhibitory activity against monoamine oxidases (IC50, 3.14 μM for MAO-B; 13.4 μM for MAO-A). Moreover, w18 could also be a metal-chelator, and able to cross the blood–brain barrier with low cell toxicity on PC12 cells. Taken together, these results suggested that w18 might be a promising multitargeted compound for AD treatment.
Novel Piperidine Derivatives. Synthesis and Anti-Acetylcholinesterase Activity of 1-Benzyl-4-piperidine Derivatives
Sugimoto, Hachiro,Tsuchiya, Yutaka,Sugumi, Hiroyuki,Higurashi, Kunizo,Karibe, Norio,et al.
, p. 1880 - 1887 (2007/10/02)
A series of 1-benzyl-4-piperidine derivatives was synthesized and evaluated for anti-acetylcholinesterase (anti-AChE) activity.Substituting the benzamide with a bulky moiety in the para position led to a substantial increase in activity.Introduction of an alkyl or phenyl group at the nitrogen atom of benzamide dramatically enhanced the activity.The basic quality of the nitrogen atom of piperidine appears to play an important role in the increased activity, since the N-benzoylpiperidine derivative was almost inactive.We found that1-benzyl-4--N-methylamino>ethyl>piperidine hydrochloride (21) (IC50 = 0.56 nM) is one of the most potent inhibitors of acetylcholinesterase.Compound 21 showed an affinity 18000 times greater for AChE than for BuChE.At a dose of 3 mg/kg, 21 produced a marked and significant increase in acetylcholine (ACh) content in the cerebral vortex and hippocampus of rats.Compound 21 was chosen for advanced development as an antidementia agent.
