203395-59-9

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Uses

Aripiprazole Bromo Impurity

Upstream product

• 110-52-1 1,4-dibromo-butane 
• 70500-72-0 7-hydroxy-1H-quinolin-2-one 
• 37783-33-8 7-(4-bromobutoxy)-2H-chromen-2-one 
• 15116-41-3 N-(3-methoxyphenyl)cinnamamide 
• 536-90-3 m-Anisidine 
• 129722-34-5 7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone 

Downstream Products

• 1354030-31-1 7-(4-(4-(2-methoxyphenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one 
• 913611-97-9 Brexpiprazole 
• 1354030-42-4 7-(4-(4-(2-isopropoxyphenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one 
• 1354030-37-7 7-(4-(4-(2-ethoxyphenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one 
• 1354030-20-8 7-(4-(4-(2,3-dichlorophenyl)-1,4-diazepan-1-yl)butoxy)quinolin-2(1H)-one 
• 1314032-23-9 7-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butoxy)quinolin-2(1H)-one 
• 129722-25-4 OPC 14857 

Relevant academic research and scientific papers

Identification, Synthesis, and Control of Process-Related Impurities in the Antipsychotic Drug Substance Brexpiprazole

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.

Synthesis and characterization of related compounds of aripiprazole, an antipsychotic drug substance

Three related compounds of aripiprazole were identified during the synthesis. These related compounds were synthesized and characterized by their respective spectral data. Copyright Taylor & Francis Group, LLC.

Design, synthesis and evaluation of quinolinone derivatives containing dithiocarbamate moiety as multifunctional AChE inhibitors for the treatment of Alzheimer’s disease

A series of novel quinolinone derivatives bearing dithiocarbamate moiety were designed and synthesised as multifunctional AChE inhibitors for the treatment of AD. Most of these compounds exhibited strong and clearly selective inhibition to eeAChE. Among them, compound 4c was identified as the most potent inhibitor to both eeAChE and hAChE (IC50 = 0.22 μM for eeAChE; IC50 = 0.16 μM for hAChE), and it was also the best inhibitor to AChE-induced Aβ aggregation (29.02% at 100 μM) and an efficient inhibitor to self-induced Aβ aggregation (30.67% at 25 μM). Kinetic and molecular modelling studies indicated that compound 4c was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 4c had good ability to cross the BBB, showed no toxicity on SH-SY5Y neuroblastoma cells and was well tolerated in mice at doses up to 2500 mg/kg (po).

7-hydroxy-2-quinolone-dithiocarbamate cholinesterase inhibitor

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

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.

Preparation method and application of substituted quinoline-2(1H)-one compound

The invention belongs to the field of pharmaceutical chemistry and chemical synthesis, and concretely relates to a preparation method of a substituted quinoline-2(1H)-one compound. The invention provides a preparation method of the substituted quinoline-2(1H)-one compound. The preparation method performs an oxidation reaction on a compound represented by a formula I and an oxidant in a solvent toobtain a compound represented by a formula II. The preparation method has the advantages of simple method, high yield and low cost and is suitable for industrial production. The substituted quinoline-2(1H)-one represented by the formula II is an important intermediate of a variety of pharmaceutical active ingredients.

Oxidative Aromatization of 3,4-Dihydroquinolin-2(1 H)-ones to Quinolin-2(1 H)-ones Using Transition-Metal-Activated Persulfate Salts

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.

Delineating an alternate convergent synthesis of brexpiprazole: a novel use of commercial 6,7-dihydrobenzo[b]thiophen-4(5H)-one as precursor to an efficacious Buchwald–Hartwig amination step

Abstract: Brexpiprazole – an anti-psychotic drug approved for the treatment of schizophrenia – has been synthesized via an extremely concise and convergent route, which involves in essence two key C–N bond formation (amination) steps that serve to link the piperazine core between the constituent benzo[b]thiophene and 7-butoxyquinolin-2(1H)-one fragments. The highlight of this synthesis is the first amination step, which was effected quite efficaciously by a novel palladium mediated Buchwald–Hartwig coupling between N-Boc-piperazine and the triflate ester of benzo[b]thiophen-4-ol (conveniently prepared in three steps from commercially available 6,7-dihydrobenzo[b]thiophen-4(5H)-one). Indeed, even without an extensive screening of catalysts, ligands and reaction conditions, this amination step could be performed quite efficiently with merely 1?mol% catalyst loading, which cleanly afforded in 87% overall yield 1-(benzo[b]thiophen-4-yl)piperazine—the starting material for the second C–N bond formation and the final step in the synthesis of Brexpiprazole. Graphical Abstract: Synopsis An alternate convergent synthesis of the anti-psychotic drug Brexpiprazole has been described. In particular, a novel palladium catalyzed Buchwald–Hartwig coupling of N-Boc-piperazine with benzo[b]thiophen-4-yl trifluoromethanesulfonate (prepared from commercially available 6,7-dihydrobenzo[b]thiophen-4(5H)-one) has been shown to furnish 1-(benzo[b]thiophen-4-yl)piperazine (a key intermediate in the synthesis of the API) in excellent yield even with 1?mol% catalyst loading. [Figure not available: see fulltext.].

Preparation method of novel brexpiprazole, aripiprazole and salts thereof

The invention provides a preparation method of novel Brexpiprazole and salts thereof, aripiprazole and salts thereof, or key intermediates thereof. The method uses a starting material of 7-hydroxycoumarin or 7-hydroxy dehydrocoumarin, which is subjected to a substitution reaction, a dehydrogenation reaction and / or amination reaction. The method has the advantages of sufficient supply of easily available raw materials, low cost, high safety, simple operation, high product yield and good quality, and is suitable for enlarge production.

FUNCTIONALLY SELECTIVE LIGANDS OF DOPAMINE D2 RECEPTORS

The present invention relates to novel functionally selective ligands of dopamine D2 receptors, including agonists, antagonists, and inverse agonists. The invention further relates to the use of these compounds for treating central nervous system disorders related to D2 receptors.