55212-32-3

Usage

Uses

Used in Scientific Research and Development:
1-(3-Methoxybenzyl)piperazine is used as a building block for creating more complex chemical structures or substances. Its unique molecular structure allows for its incorporation into various compounds, making it a valuable asset in the field of chemistry.
Used in Pharmaceutical Industry:
1-(3-Methoxybenzyl)piperazine is used as an intermediate in the synthesis of pharmaceutical compounds. Its versatile chemical properties enable it to be a key component in the development of new drugs and medications.
Used in Chemical Synthesis:
1-(3-Methoxybenzyl)piperazine is used as a reagent in chemical synthesis processes. Its ability to form stable bonds with other molecules makes it a useful tool in the production of a wide range of chemical products.

InChI:InChI=1/C12H18N2O/c1-15-12-4-2-3-11(9-12)10-14-7-5-13-6-8-14/h2-4,9,13H,5-8,10H2,1H3

Upstream product

• 110-85-0 piperazine 
• 824-98-6 m-methoxybenzyl chloride 
• 874-98-6 1-bromomethyl-3-methoxybenzene 
• 77278-57-0 tert-butyl 4-(3-methoxybenzyl)piperazine-1-carboxylate 

Downstream Products

• 102535-35-3 4-Methoxy-3-[4-(3-methoxy-benzyl)-piperazine-1-carbonyl]-benzenesulfonamide 
• 549510-93-2 4-(3-Methoxy-benzyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester 
• 1164101-51-2 2-(4-(3-methoxybenzyl)piperazin-1-yl)-N-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-7-yl)acetamide 
• 1192322-81-8 3-{4-[(3-methoxycarbonylphenylcarbamoyl)-methoxy]-phenyl}-[4-(3-methoxybenzyl)piperazin-1-yl]-adamantan-1-ylmethanone 
• 1289155-20-9 (S)-2-((1-(benzylsulfonyl)pyrrolidin-3-yl)amino)-1-(4-(3-methoxybenzyl)piperazin-1-yl)ethanone 
• 1610627-11-6 C₂₅H₂₆N₄O₃ 

Relevant academic research and scientific papers

Synthesis and preclinical evaluation of [11C]MA-PB-1 for in?vivo imaging of brain monoacylglycerol lipase (MAGL)

MAGL is a potential therapeutic target for oncological and psychiatric diseases. Our objective was to develop a PET tracer for in?vivo quantification of MAGL. We report [11C]MA-PB-1 as an irreversible MAGL inhibitor PET tracer. The in?vitro inh

Design, synthesis and SAR of antitubercular benzylpiperazine ureas

Abstract: N-furfuryl piperazine ureas disclosed by scientists at GSK Tres Cantos were chosen as antimycobacterial hits from a phenotypic whole-cell screen. Bioisosteric replacement of the furan ring in the GSK Tres Cantos molecules with a phenyl ring led to molecule (I) with an MIC of 1?μM against Mtb H37Rv, low cellular toxicity (HepG2 IC50 ~ 80?μM), good DMPK properties and specificity for Mtb. With the aim of delineating the SAR associated with (I), fifty-five analogs were synthesized and screened against Mtb. The SAR suggests that the piperazine ring, benzyl urea and piperonyl moieties are essential signatures of this series. Active compounds in this series are metabolically stable, have low cellular toxicity and are valuable leads for optimization. Molecular docking suggests these molecules occupy the Q0 site of QcrB like Q203. Graphic Abstract: Bioisosteric replacement of N-furfuryl piperazine-1-carboxamides yielded molecule (I) a novel lead with satisfactory PD, metabolism, and toxicity profiles.[Figure not available: see fulltext.]

Further SAR studies on natural template based neuroprotective molecules for the treatment of Alzheimer's disease

In our earlier paper, we described ferulic acid (FA) template based novel series of multifunctional cholinesterase (ChE) inhibitors for the management of AD. This report has further extended the structure–activity relationship (SAR) studies of this series of molecules in a calibrated manner to improve upon the ChEs inhibition and antioxidant property to identify the novel potent multifunctional molecules. To investigate the effect of replacement of phenylpiperazine ring with benzylpiperazine, increase in the linker length between FA and substituted phenyl ring, and replacement of indole moiety with tryptamine on this molecular template, three series of novel molecules were developed. All synthesized compounds were tested for their acetyl and butyryl cholinestrases (AChE and BChE) inhibitory properties. Enzyme inhibition and PAS binding studies identified compound 13b as a lead molecule with potent inhibitor property towards AChE/BChE (AChE IC50 = 0.96 ± 0.14 μM, BChE IC50 = 1.23 ± 0.23 μM) compared to earlier identified lead molecule EJMC-G (AChE IC50 = 5.74 ± 0.13 μM, BChE IC50 = 14.05 ± 0.10 μM, respectively). Molecular docking and dynamics studies revealed that 13b fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Trp86, Ser125, Glu202, Trp 286, Phe295, Tyr 337 in AChE, and with Trp 82, Gly115, Tyr128, and Ser287 in BChE. The compound, 13b was found to be three times more potent antioxidant in a DPPH assay (IC50 = 20.25 ± 0.26 μM) over the earlier identified EJMC-B (IC50 = 61.98 ± 0.30 μM) and it also was able to chelate iron. Co-treatment of 13b with H2O2, significantly attenuated and reversed H2O2-induced toxicity in the SH-SY5Y cells. The parallel artificial membrane permeability assay-blood brain barrier (PAMPA-BBB) revealed that 13b could cross BBB efficiently. Finally, the in-vivo efficacy of 13b at dose of 10 mg/kg in scopolamine AD model has been demonstrated. The present study strongly suggests that the naturally inspired multifunctional molecule 13b may behave as a potential novel therapeutic agent for AD management.

Synthesis of 17β-hydroxysteroid dehydrogenase type 10 steroidal inhibitors: Selectivity, metabolic stability and enhanced potency

17beta-Hydroxysteroid dehydrogenase type 10 (17β-HSD10) is the only mitochondrial member of 17β-HSD family. This enzyme can oxidize estradiol (E2) into estrone (E1), thus reducing concentration of this neuroprotective steroid. Since 17β-HSD10 possesses properties that suggest a possible role in Alzheimer's disease, its inhibition appears to be a therapeutic strategy. After we identified the androsterone (ADT) derivative 1 as a first steroidal inhibitor of 17β-HSD10, new analogs were synthesized to increase the metabolic stability, to improve the selectivity of inhibition over 17β-HSD3 and to optimize the inhibitory potency. From six D-ring derivatives of 1 (17-C[dbnd]O), two compounds (17β-H/17α-OH and 17β-OH/17α-C[tbnd]CH) were more metabolically stable and did not inhibit the 17β-HSD3. Moreover, solid phase synthesis was used to extend the molecular diversity on the 3β-piperazinylmethyl group of the steroid base core. Eight over 120 new derivatives were more potent inhibitors than 1 for the transformation of E2 to E1, with the 4-(4-trifluoromethyl-3-methoxybenzyl)piperazin-1-ylmethyl-ADT (D-3,7) being 16 times more potent (IC50 = 0.14 μM). Finally, D-ring modification of D-3,7 provided 17β-OH/17α-C[tbnd]CH derivative 25 and 17β-H/17α-OH derivative 26, which were more potent inhibitor than 1 (1.8 and 2.4 times, respectively).

A2B Adenosine Receptor Antagonists with Picomolar Potency

The A2B adenosine receptor (A2BAR) was proposed as a novel target for the (immuno)therapy of cancer since A2BAR blockade results in antiproliferative, antiangiogenic, antimetastatic, and immunostimulatory effects. In this study, we explored the structure-activity relationships of xanthin-8-yl-benzenesulfonamides mainly by introducing a variety of linkers and substituents attached to the sulfonamide residue. A new, convergent strategy was established, which facilitated the synthesis of the target compounds. Many of the new compounds exhibited subnanomolar affinity for the A2BAR combined with high selectivity. Functional groups were introduced, which will allow the attachment of dyes and other reporter groups. 8-(4-((4-(4-Bromophenyl)piperazin-1-yl)sulfonyl)phenyl)-1-propylxanthine (34, PSB-1901) was the most potent A2B-antagonist (Ki 0.0835 nM, KB 0.0598 nM, human A2BAR) with >10 000-fold selectivity versus all other AR subtypes. It was similarly potent and selective at the mouse A2BAR, making it a promising tool for preclinical studies. Computational studies predicted halogen bonding to contribute to the outstanding potency of 34.

Sulfonamides incorporating piperazine bioisosteres as potent human carbonic anhydrase I, II, IV and IX inhibitors

Starting from the molecular simplification of (R) 4-(3,4-dibenzylpiperazine-1-carbonyl)benzenesulfonamide 9a, a compound endowed with selectivity for human Carbonic Anhydrase (hCA) IV, a series of piperazines and 4-aminopiperidines carrying a 4-sulfamoylb

Development of 2-amino-4-phenylthiazole analogues to disrupt myeloid differentiation factor 88 and prevent inflammatory responses in acute lung injury

Myeloid differentiation primary response protein 88 (MyD88), an essential adapter protein used by toll-like receptors (TLR), is a promising target molecule for the treatment of respiratory inflammatory diseases. Previous studies explored the activities of novel 2-amino-4-phenylthiazole analogue (6) in inflammation-induced cancer, and identified the analogue as an inhibitor of MyD88 toll/interleukin-1 receptor (TIR) homology domain dimerization. Here, we describe the synthesis of 47 new analogues by modifying different sites on this lead compound and assessed their anti-inflammatory activities in lipopolysaccharide-induced mouse primary peritoneal macrophages (MPMs). The most promising compound, 15d, was found to effectively interact with MyD88 protein and prevented formation of the MyD88 homodimeric complex. Furthermore, 15d showed in vivo anti-inflammatory activity in LPS-caused model of acute lung injury. This work provides new candidates as MyD88 inhibitors to combat inflammation diseases.

Design, synthesis, and evaluation of genipin derivatives for the treatment of Alzheimer's Disease

Twenty-two novel genipin derivatives have been designed, synthesized, and evaluated for their inhibitory activity against acetylcholinesterase (AChE). As a result, compound 13a bearing ligustrazine moiety displayed the most potent AChE inhibitory activity in this series with IC50 value of 218?nm. Besides, MTT assay was performed to investigate the neuroprotection of these compounds against PC12 cells injured by Amyloid β-protein 1–42 (Aβ1–42). Among them, 8a showed higher inhibition rate (%Inhibition?=?22.29) than the positive reference Donepezil (%Inhibition?=?17.65).

The synthesis and biological evaluation of novel gardenamide A derivatives as multifunctional neuroprotective agents

A novel series of gardenamide A derivatives was synthesized as potential anti-Alzheimer's disease agents. The neuroprotective effects of these multifunctional agents against oxygen-glucose deprivation (OGD)-induced neurotoxicity in rat cortical neurons, and hydrogen peroxide (H2O2)- A nd amyloid-β1-42 (Aβ1-42)-induced neurotoxicity in rat hippocampal neurons were evaluated. In vitro studies revealed that these compounds demonstrated moderate to good multifunctional neuroprotective activity. Among the entire series, compounds 10e, 10j, 10n and 10p appeared to be the most active multifunctional neuroprotective agents. Studies indicate that compounds 10e, 10f, 10h, 10i, 10j, 10n and 10p exhibit significant activities against OGD-induced neurotoxicity in rat cortical neurons, and 10e, 10j, 10n and 10p show prominent activities against H2O2- A nd Aβ1-42-induced neurotoxicity in rat hippocampal neurons. Moreover, these derivatives did not exert conspicuous neurotoxicity in rat cortical neurons. Thus, the present study evidently shows that 10e, 10j, 10n and 10p are potent multifunctional neuroprotective agents, which may serve as promising lead candidates for anti-Alzheimer's disease drug development.

Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors

Based on the literature-reported compensatory effect of PI3K on Abl inhibition and the improved preclinical effect of drug combination of Abl and PI3K inhibitors, a series of compounds bearing novel scaffold of (S)-3-aminopyrrolidine was identified as Abl and PI3K dual inhibitors through support vector machine screening tool, which were subsequently synthesized and tested. Most compounds demonstrated promising cytoxicity against a CML leukemia cell-line K562 and moderate inhibition against Abl and PI3K kinases. These compounds induced no apoptosis in K562 cell-line, suggesting that their cytotoxic activities are unlikely duo to other known anti-CML mechanisms. Molecular docking study further showed that the compound 5k could bind with both Abl and PI3K, but the weaker binding with Abl compared to Imatinib is consistent with its low kinase inhibitory rates. These plus literature-reported evidences suggest that the promising cytotoxic effect of our novel compounds might be due to the collective effect of Abl and PI3K inhibition.