586345-73-5Relevant academic research and scientific papers
N-Propargylamine-hydroxypyridinone hybrids as multitarget agents for the treatment of Alzheimer's disease
Guo, Jianan,Zhang, Yujia,Zhang, Changjun,Yao, Chuansheng,Zhang, Jingqi,Jiang, Xiaoying,Zhong, Zhichao,Ge, Jiamin,Zhou, Tao,Bai, Renren,Xie, Yuanyuan
, (2021/06/07)
AD is a progressive brain disorder. Because of the lack of remarkable single-target drugs against neurodegenerative disorders, the multitarget-directed ligand strategy has received attention as a promising therapeutic approach. Herein, we rationally designed twenty-nine hybrids of N-propargylamine-hydroxypyridinone. The designed hybrids possessed excellent iron-chelating activity (pFe3+ = 17.09–22.02) and potent monoamine oxidase B inhibitory effects. Various biological evaluations of the optimal compound 6b were performed step by step, including inhibition screening of monoamine oxidase (hMAO-B IC50 = 0.083 ± 0.001 μM, hMAO-A IC50 = 6.11 ± 0.08 μM; SI = 73.5), prediction of blood–brain barrier permeability and mouse behavioral research. All of these favorable results proved that the N-propargylamine-hydroxypyridinone scaffold is a promising structure for the discovery of multitargeted ligands for AD therapy.
Pyridone hexa-alkyne amine modified derivative and preparation method and application thereof
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Paragraph 0085; 0089, (2021/03/30)
The invention relates to a pyridone hexa-alkyne amine modified derivative as shown in a formula (I) and a pharmaceutically acceptable salt thereof, a preparation method thereof, application of the pyridone hexa-alkyne amine modified derivative or the pharmaceutically acceptable salt thereof to preparation of drugs for preventing or treating related diseases, especially Alzheimer's disease and Parkinson's disease, by inhibiting monoamine oxidase, chelating metal iron ions, resisting Abeta and resisting oxidation. According to the invention, a series of novel single-molecule multi-target anti-ADactive compounds are synthesized, and pyridone derivatives with iron ion chelating activity and propynylamine with MAOB inhibitory activity are creatively and organically combined together, so that the compounds have remarkable advantages on Alzheimer's disease with complex pathogenesis; and the combined molecules are far superior to CP20 (deferiprone) in the aspect of iron ion chelating activity.
Synthesis, anti-HIV-1 and antiproliferative evaluation of novel 4-nitroimidazole derivatives combined with 5-hydroxy-4-pyridinone moiety
Shirvani, Pouria,Fassihi, Afshin,Saghaie, Lotfollah,Van Belle, Siska,Debyser, Zeger,Christ, Frauke
, (2019/11/26)
In an effort to synthesize more effective non-nucleoside reverse transcriptase inhibitors (NNRTIs) against the HIV-1 infection, a new series of novel 4-nitroimidazole derivatives combined with 5-hydroxy-4-pyridinone moiety were designed by molecular docking studies, prepared and characterized by spectroscopic techniques. All the synthesized compounds were in vitro evaluated for their inhibitory effect against the HIV-1 replication in the MT-4 cells. Results showed that none of these synthesized compounds displayed any specific anti HIV-1 activity. Surprisingly, these compounds showed high cytotoxicity against MT-4 cells with low selectivity index (50 = 1.3 μM and EC50 = 1.8 μM respectively).
Kojic acid derived hydroxypyridinone-chloroquine hybrids: Synthesis, crystal structure, antiplasmodial activity and β-haematin inhibition
Andayi, Warren Andrew,Egan, Timothy J.,Chibale, Kelly
supporting information, p. 3263 - 3267 (2014/07/22)
Aminochloroquinoline-kojic acid hybrids were synthesized and evaluated for β-haematin inhibition and antiplasmodial activity against drug resistant (K1) and sensitive (3D7) strains of Plasmodium falciparum. Compound 7j was the most potent compound in both strains (IC503D7 = 0.004 μM; IC50K1 = 0.03 μM) and had the best β-haematin inhibition activity (0.07 IC50 equiv vs 1.91 IC 50 equiv for chloroquine). One compound 8c was found to be equipotent in both strains (IC50 = 0.04 μM).
Synthesis and cytotoxicity evaluation of metal-chelator-bearing flavone, carbazole, dibenzofuran, xanthone, and anthraquinone
Chen, Yeh-Long,Chen, Po-Hsu,Chung, Chao-Ho,Li, Kuang-Chieh,Jeng, Haw-Yaun,Tzeng, Cherng-Chyi
, p. 778 - 786 (2007/10/03)
2-(Aryloxymethyl)-5-benzyloxy-1-methyl-1H-pyridin-4-ones 8a-8g, 2-(aryloxymethyl)-5-hydroxy-4H-pyran-4-ones 9a-9g, and 2-(aryloxymethyl)-5-hydroxy-1-methyl-1H-pyridin-4-ones 10a-10g were prepared from the known 5-benzyloxy-2-(hydroxymethyl)pyran-4-one (3) in a good overall yield. These compounds were evaluated in vitro against a three-cell lines panel consisting of MCF7 (breast), NCI-H460 (lung), and SF-268 (CNS), and the active compounds passed on for evaluation in the full panel of 60 human tumor cell lines derived from nine cancer cell types. The results indicated that 5-hydroxy derivatives are more favorable than their corresponding 5-benzyloxy precursors (10a-10g vs. 8a-8g), and 1-methyl-1H-pyridin-4-ones are more favorable than their corresponding pyran-4(1H)-ones (10a-10g vs. 9a-9g). Among these three types of compounds, 2-(aryloxymethyl)-5-hydroxy-1-methyl-1H-pyridin-4-ones 10a-10g were the most cytotoxic; they inhibited the growth of almost all the cancer cells tested. On the contrary, compound 8a (a mean GI50 = 27.8 μM), 8b (38.5), 8d (11.0), and 8e (30.5) are especially active against the growth of SK-MEL-5 (a melanoma cancer cell) with a GI50 of 0.01, 5.65, 0.55, and 0.03 μM, respectively (cf. Table 2).
