52313-53-8Relevant academic research and scientific papers
Acylhydrazone compound as well as pharmaceutical composition and application thereof
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Paragraph 0121; 0123; 0125; 0130-0131; 0146-0152, (2020/11/25)
The invention relates to an acylhydrazone compound as well as a pharmaceutical composition and application thereof. According to the main technical scheme, the structure of the acylhydrazone compoundis as shown in one of a general formula (I), a general formula (II) and a general formula (III); wherein V1, W1, X1, Y1 and Z1 are independently selected from one of the following groups: N and C-R13;A2, B2, D2, E2, G2, J2, L2, T3, V3, U3, W3, X3, Y3 and Z3 are independently selected from one of the following groups: N and C-R4; R11, R21 and R31 are independently selected from one of the following groups: hydrogen-H and a first chain alkyl. The pharmaceutical composition comprises the acylhydrazone compound. The method is mainly used for designing the acylhydrazone compound. The acylhydrazonecompound and the pharmaceutical composition taking the acylhydrazone compound as an active ingredient can be used as an acetylcholin esterase AChE inhibitor and used for preparing a medicine for treating Alzheimer's disease.
Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine N-benzylpiperidine fragments
Zhou, Yeheng,Sun, Wei,Peng, Jiale,Yan, Hui,Zhang, Li,Liu, Xingyong,Zuo, Zhili
, (2019/10/08)
Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC50 value of 6.62 nM against AChE, while almost no inhibitory effect against BChE. ADMET predictions and PAMPA permeability evaluation showed good drug-like property. The higher activity with an intermediate alkyl chain substitution indicates a new binding mode of inhibitor with AChE. This finding provides new insights into the binding mechanism and is helpful for discovery of novel high-activity AChE inhibitors.
Discovery of potent and selective inhibitors of the mammalian target of rapamycin (mTOR) kinase
Nowak, Pawel,Cole, Derek C.,Brooijmans, Natasja,Bursavich, Matthew G.,Curran, Kevin J.,Ellingboe, John W.,Gibbons, James J.,Hollander, Irwin,Hu, YongBo,Kaplan, Joshua,Malwitz, David J.,Toral-Barza, Lourdes,Verheijen, Jeroen C.,Zask, Arie,Zhang, Wei-Guo,Yu, Ker
experimental part, p. 7081 - 7089 (2010/04/29)
The mammalian target of rapamycin (mTOR) is a central regulator of cell growth, metabolism, and angiogenesis and an emerging target in cancer research. High throughput screening (HTS) of our compound collection led to the identification of 3-(4-morpholin-4-yl-1-piperidin-4-yl-1H-pyrazolo[3,4-d] pyrimidin-6-yl)phenol (5a), a modestly potent and nonselective inhibitor of mTOR and phosphoinositide 3-kinase (PI3K). Optimization of compound 5a, employing an mTOR homology model based on an X-ray crystal structure of closely related PI3Kγ led to the discovery of 6-(1H-indol-5-yl)-4-morpholin-4-yl-1-[1- (pyridin-3-ylmethyl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidine (5u), a potent and selective mTOR inhibitor (mTOR IC50 = 9 nM; PI3Kα IC 50 = 1962 nM). Compound 5u selectively inhibited cellular biomarker of mTORC1 (P-S6K, P-4EBP1) and mTORC2 (P-AKT S473) over the biomarker of PI3K/PDK1 (P-AKT T308) and did not inhibit PI3K-related kinases (PIKKs) in cellular assays. These pyrazolopyrimidines represent an exciting new series of mTOR-selective inhibitors with potential for development for cancer therapy. 2009 American Chemical Society.
