203395-59-9Relevant articles and documents
Identification, Synthesis, and Control of Process-Related Impurities in the Antipsychotic Drug Substance Brexpiprazole
Tyagi, Rahul,Singh, Harnam,Singh, Jagat,Arora, Himanshu,Yelmeli, Vijayalaxmi,Jain, Mohit,Girigani, Sathyanarayana,Kumar, Pramod
, p. 1471 - 1480 (2018)
This article describes the identification, synthesis, and control of several unknown related substances present in the form of critical impurities that were observed during the process development for the antipsychotic drug substance brexpiprazole (BRX). On the basis of liquid chromatography-mass spectrometry (LC-MS) evidence of impurities and analysis of the employed synthetic route of BRX, the structures of the unknown impurities were proposed. Many critical impurities were synthesized, and their chemical structures were established using different spectroscopy techniques. To the best of our knowledge, this is the first report where several new impurities were recognized, addressed, and controlled effectively during the development of a robust and efficient process for the BRX drug substance.
7-hydroxy-2-quinolone-dithiocarbamate cholinesterase inhibitor
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Paragraph 0024, (2020/02/29)
The invention relates to the field of pharmaceutical chemistry, in particular to a 7-hydroxy-2-quinolone-dithiocarbamate compound shown as a formula I (Please see the specifications for the formula I). A pharmacodynamic experiment proves that the compound can serve as a cholinesterase inhibitor and can be clinically used for treating Alzheimer's disease (AD). In the formula I, R1 represents -H or-CH3, R2 represents -H or -CH3, R3 represents cyclic secondary amine substituent groups shown in the specification, and n is equal to 2-6.
Acetylcholinesterase inhibition of diversely functionalized quinolinones for alzheimer’s disease therapy
Bautista-Aguilera, óscar M.,Ismaili, Lhassane,Chioua, Mourad,Andrys, Rudolf,Schmidt, Monika,Bzonek, Petr,Martínez-Grau, María ángeles,Beadle, Christopher D.,Vetman, Tatiana,López-Mu?oz, Francisco,Iriepa, Isabel,Refouvelet, Bernard,Musilek, Kamil,Marco-Contelles, José
, p. 1 - 20 (2020/06/22)
In this communication, we report the synthesis and cholinesterase (ChE)/monoamine oxidase (MAO) inhibition of 19 quinolinones (QN1-19) and 13 dihydroquinolinones (DQN1-13) designed as potential multitarget small molecules (MSM) for Alzheimer’s disease therapy. Contrary to our expectations, none of them showed significant human recombinant MAO inhibition, but compounds QN8, QN9, and DQN7 displayed promising human recombinant acetylcholinesterase (hrAChE) and butyrylcholinesterase (hrBuChE) inhibition. In particular, molecule QN8 was found to be a potent and quite selective non-competitive inhibitor of hrAChE (IC50 = 0.29 μM), with Ki value in nanomolar range (79 nM). Pertinent docking analysis confirmed this result, suggesting that this ligand is an interesting hit for further investigation.
Oxidative Aromatization of 3,4-Dihydroquinolin-2(1 H)-ones to Quinolin-2(1 H)-ones Using Transition-Metal-Activated Persulfate Salts
Chen, Weiming,Sun, Changliang,Zhang, Yan,Hu, Tianwen,Zhu, Fuqiang,Jiang, Xiangrui,Abame, Melkamu Alemu,Yang, Feipu,Suo, Jin,Shi, Jing,Shen, Jingshan,Aisa, Haji A.
, p. 8702 - 8709 (2019/07/03)
Inorganic persulfate salts were identified as efficient reagents for the oxidative aromatization of 3,4-dihydroquinolin-2(1H)-ones through the activation of readily available transition metals, such as iron and copper. The feasible protocol conforming to the requirement of green chemistry was utilized in the preparation of the key intermediate (7-(4-chlorobutoxy)quinolin-2(1H)-one 2) of brexpiprazole in 80% isolated yield on a 100 g scale, and different quinolin-2(1H)-one derivatives with various functional groups were demonstrated in 52-89% yields.
