70849-64-8

Usage

Uses

Used in Pharmaceutical and Agrochemical Industries:
1-(4-methoxyphenyl)piperazine hydrochloride is used as an intermediate in the synthesis of various pharmaceuticals and agrochemicals for its ability to contribute to the development of new drugs and chemical products.
Used in Drug Production:
1-(4-methoxyphenyl)piperazine hydrochloride serves as a precursor in the production of a variety of drugs, playing a crucial role in the manufacturing process of medicinal agents.
Used in Neurodegenerative and Psychiatric Disorder Treatment:
1-(4-methoxyphenyl)piperazine hydrochloride is used as a potential therapeutic agent for the treatment of neurodegenerative diseases and psychiatric disorders, due to its capacity to modulate the activity of specific neurotransmitter systems in the brain.

Upstream product

• 696-62-8 para-iodoanisole 
• 821-48-7 bis-(2-chloroethyl)amine hydrochloride 
• 104-94-9 4-methoxy-aniline 

Downstream Products

• 727361-86-6 (2-chlorophenyl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone 
• 727361-87-7 (3-chlorophenyl)(4-(4-methoxyphenyl)piperazin-1-yl)methanone 
• 675860-72-7 (thiophen-2-yl) (4-(4-methoxyphenyl)piperazin-1-yl)methanone 
• 800371-38-4 1-isovaleryl-4-(4-methoxyphenyl)piperazine 
• 112559-81-6 N-(4-Hydroxyphenyl)-N'-(4'-nitrophenyl)-piperazine 

Relevant academic research and scientific papers

Design, synthesis and anticancer activity of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-1,2,3-thiadiazoles as microtubule-destabilizing agents

Hereby, we report our efforts on discovery and optimization of a new series of 5-aryl-4-(4-arylpiperazine-1-carbonyl)-1,2,3-thiadiazoles as new microtubule-destabilizing agents along our previous study. Guided by docking model analysis, we introduced the 1,2,3-thiadiazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. Extensive structure modifications were performed to investigate the detailed structure and activity relationships (SARs). Some compounds exhibited potent antiproliferative activities against three human cancer cell lines (SGC-7901, A549 and HeLa). The compound 5m exhibited the highest potency against the three cancer cell lines. The tubulin polymerization experiments indicated that compound 5m effectively inhibited the tubulin polymerization, and immunostaining assay revealed that it significantly disrupted microtubule dynamics. Moreover, cell cycle studies revealed that compound 5m dramatically arrested cell cycle progression at G2/M phase.

Design, synthesis and biological evaluation of 1-Aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as novel microtubule destabilizers

A series of 1-aryl-5-(4-arylpiperazine-1-carbonyl)-1H-tetrazols as microtubule destabilizers were designed, synthesised and evaluated for anticancer activity. Based on bioisosterism, we introduced the tetrazole moiety containing the hydrogen-bond acceptors as B-ring of XRP44X analogues. The key intermediates ethyl 1-aryl-1H-tetrazole-5-carboxylates 10 can be simply and efficiently prepared via a microwave-assisted continuous operation process. Among the compounds synthesised, compound 6–31 showed noteworthy potency against SGC-7901, A549 and HeLa cell lines. In mechanism studies, compound 6–31 inhibited tubulin polymerisation and disorganised microtubule in SGC-7901 cells by binding to tubulin. Moreover, compound 6–31 arrested SGC-7901cells in G2/M phase. This study provided a new perspective for development of antitumor agents that target tubulin.

Design, synthesis and evaluation of antiproliferative and antitubulin activities of 5-methyl-4-aryl-3-(4-arylpiperazine-1-carbonyl)-4H-1,2,4-triazoles

A series of novel 5-methyl-4-aryl-3-(4-arylpiperazine-1-carbonyl)-4H-1,2,4-triazoles possessing 1,2,4-triazole as the hydrogen-bond acceptor were designed, synthesized and evaluated for their antiproliferative and tubulin polymerization inhibitory activities. Some of them exhibited moderate activities in vitro against the three cancer cell lines including SGC-7901, A549 and HeLa. Compound 6e exhibited the highest potency against the three cancer cell lines. Moreover, the tubulin polymerization experiments indicated that compound 6e could inhibit the tubulin polymerization. Immunofluorescence study and cell cycle analysis clearly revealed compound 6e could disrupt intracellular microtubule organization, arrest cell cycle at the G2/M phase. In addition, molecular docking analysis demonstrated the interaction of compound 6e at the colchicine-binding site of tubulin. These preliminary results suggested that compound 6e is a new colchicine binding site inhibitor and worthy of further investigation.

Design, synthesis and biological evaluation of novel naturally-inspired multifunctional molecules for the management of Alzheimer's disease

In our overall goal to overcome the limitations associated with natural products for the management of Alzheimer's disease and to develop in-vivo active multifunctional cholinergic inhibitors, we embarked on the development of ferulic acid analogs. A systematic SAR study to improve upon the cholinesterase inhibition of ferulic acid with analogs that also had lower logP was carried out. Enzyme inhibition and kinetic studies identified compound 7a as a lead molecule with preferential acetylcholinesterase inhibition (AChE IC50 = 5.74 ± 0.13 μM; BChE IC50 = 14.05 ± 0.10 μM) compared to the parent molecule ferulic acid (% inhibition of AChE and BChE at 20 μM, 15.19 ± 0.59 and 19.73 ± 0.91, respectively). Molecular docking and dynamics studies revealed that 7a fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Asp74, Trp286, and Tyr337 in AChE and with Tyr128, Trp231, Leu286, Ala328, Phe329, and Tyr341 in BChE. Compound 7a was found to be an efficacious antioxidant in a DPPH assay (IC50 = 57.35 ± 0.27 μM), and it also was able to chelate iron. Data from atomic force microscopy images demonstrated that 7a was able to modulate aggregation of amyloid β1-42. Upon oral administration, 7a exhibited promising in-vivo activity in the scopolamine-induced AD animal model and was able to improve spatial memory in cognitive deficit mice in the Y-maze model. Analog 7a could effectively reverse the increased levels of AChE and BChE in scopolamine-treated animals and exhibited potent ex-vivo antioxidant properties. These findings suggest that 7a can act as a lead molecule for the development of naturally-inspired multifunctional molecules for the management of Alzheimer's and other neurodegenerative disorders.

ANTI-PAIN COMPOUND AND PREPARATION METHOD THEREFOR

Disclosed are a compound represented by the general Formula (I), or a stereisomer, tautomer, derivative, prodrug or pharmaceutically acceptable salt thereof, and a method for preparing the compound and use of the compound in manufacture of a medicament for treating a neuropathic pain and/or neuropathic pain syndrome or a medicament for combating an inflammation: wherein R1 is selected from hydrogen, halogen, alkyl, cyano and haloalkyl, R2 and R3 are independently selected from hydrogen, halogen, alkyl, haloalkyl and nitro, and R1, R2 and R3 are not hydrogen at the same time; furthermore, when either R2 or R3 is nitro or halogen, the other two of R1, R2 and R3 are not hydrogen at the same time. The compound has good effects in treating a neuropathic pain and/or neuropathic pain syndrome and good effects in combating an inflammation, and has not side effects such as addiction.

Design, synthesis and docking study of 4-arylpiperazine carboxamides as monoamine neurotransmitters reuptake inhibitors

Rational drug design method has been used to generate 4-arylpiperazine carboxamides in an effort to develop safer, more potent and effective monoamine neurotransmitters reuptake inhibitors. Out of twenty-seven synthesized compounds, compound 9 displayed potent monoamine neurotransmitter reuptake inhibitory activity against HEK cells transfected with hSERT or hNET. A Surflex-Dock docking model of 9 was also studied.

Preparation process of posaconazole intermediate 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine

The invention relates to the technical field of chemical medicine synthesis, in particular to a preparation process of posaconazole intermediate 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine. The preparation process provided by the invention comprises the following steps of a, preparing methoxyphenyl piperazine hydrochloride; b, preparing p-hydroxyphenyl piperazine hydrobromide; c, preparing 1-(4-hydroxyphenyl)-4-(4-nitrophenyl)piperazine; d, preparing a crude product of 1-(4-hydroxyphenyl)-4-(4-aminophenyl)piperazine; e, purifying a product. Cheap solvents and high-activity nickel catalystsare selected and used; low-pressure hydrogenation reaction is used; the raw material cost is greatly reduced; important links such as nickel ion removal and aluminum ion removal are used for post treatment; the product quality reaches the content of 99.2 percent; the single maximum noise peak value is less than 0.1 percent; the total noise peak value is less than 1.0 percent; the home and abroadmarket competitive power of the product is greatly enhanced.

Exploration of substituted arylpiperazine–tetrazoles as promising dual norepinephrine and dopamine reuptake inhibitors

In the search for potent dual norepinephrine and dopamine reuptake inhibitors, several substituted arylpiperazine–tetrazoles were designed, synthesized and evaluated for their neurotransmitter reuptake inhibitory activities. Various derivatives exhibited selective and strong neurotransmitter reuptake inhibitory activity. In particular, compounds with a three-carbon linker displayed selective and stronger potency than those with two-carbon and four-carbon linkers. Interestingly, six compounds, 9b, 9c, 9d, 9o, 9q and 9u displayed more effective activity than the standard drug, bupropion. The provided SAR data and potent biological activity can offer useful guidelines for designing dual norepinephrine and dopamine reuptake inhibitors as effective therapeutic agents for treatment of several central nervous system diseases.

Discovery of novel N,N-3-phenyl-3-benzylaminopropionanilides as potent inhibitors of cholesteryl ester transfer protein in vivo

Epidemiological studies have identified that the risk of cardiovascular events increases due to the decreased levels of high density lipoprotein-cholesterol and the elevated levels of low density lipoprotein-cholesterol. Herein, we report a novel series of N,N-3-phenyl-3-benzylaminopropionanilide derivatives, which were identified as potent cholesteryl ester transfer protein (CETP) inhibitor. The initial lead compound L10 (IC50 8.06 μM) was found by pharmacophore-based virtual screening (Dong-Mei Zhao et al., Chin. Chem. Lett. 2014, 25, 299). After systematic structure variation and biological testing against CETP, two different series were identified as scaffolds for potent CETP inhibitors. One is N,N-3-phenyl-3-benzylaminopropanamide derivatives, which were investigated in our previous paper (Bioorg. Med. Chem. 2015, doi: http://dx.doi.org/10.1016/j.bmc.2015.12.010). The most potent compound HL16 in that series has the IC50 of 0.69 μM. The other series is N,N-3-phenyl-3-benzylaminopropionanilide derivatives, which was investigated in current study. Further optimization of the structure-activity relationship (SAR) resulted in H16 (IC50 0.15 μM), which was discovered as a potent CETP inhibitor in vitro by BODIPY-CE fluorescence assay. In addition, the results of pharmacodynamics studies showed that H16 exhibited both favorable HDL-C enhancement and LDL-C reduction in vivo by hamster. It also has an excellent stability in rat liver microsomal.

Design, synthesis and biological evaluation of N,N-3-phenyl-3-benzylaminopropanamide derivatives as novel cholesteryl ester transfer protein inhibitor

A series of N,N-3-phenyl-3-benzylaminopropanamide derivatives were identified as novel CETP (cholesteryl ester transfer protein) inhibitors. In our previous study, lead compound L10 was discovered by pharmacophore-based virtual screening (Dong-Mei Zhao et al., 2014). Based on L10 (IC50 8.06 μM), compound HL6 (IC50 10.7 μM) was discovered following systematic structure variation and biological tests. Further optimization of the structure-activity relationship (SAR) resulted in N,N-3-phenyl-3-benzylaminopro panamides derivatives as novel CETP inhibitors. They were synthesized and evaluated against CETP by BODIPY-CE fluorescence assay. Among them, HL16 (IC50 0.69 μM) was a highly potent CETP inhibitor in vitro. In addition, HL16 exhibited favorable HDL-C enhancement and LDL-C reduction in vivo by hamster. The molecular docking of HL16 into the CETP was performed. The binding mode demonstrated that HL16 occupied the CETP binding site and formed interactions with the key amino acid residues.