52146-35-7

Usage

Uses

Used in Pharmaceutical Industry:
1-(3,4,5-TRIMETHOXY-BENZYL)-PIPERAZINE is used as an impurity in the context of Trimetazidine (T795610) for [application reason]. 1-(3,4,5-TRIMETHOXY-BENZYL)-PIPERAZINE may be relevant in the quality control and manufacturing processes of Trimetazidine to ensure the purity and safety of the final drug product.
(Note: The application reason is not provided in the materials, so it is left as a placeholder. If there is a specific reason for its use as an impurity, it should be included in the description.)

InChI:InChI=1/C14H22N2O3/c1-17-12-8-11(9-13(18-2)14(12)19-3)10-16-6-4-15-5-7-16/h8-9,15H,4-7,10H2,1-3H3

Upstream product

• 110-85-0 piperazine 
• 3840-30-0 5-(chloromethyl)-1,2,3-trimethoxybenzene 
• 415929-95-2 4-(3,4,5-trimethoxy-benzyl)-piperazine-1-carboxylic acid ethyl ester 
• 86-81-7 3,4,5-trimethoxy-benzaldehyde 

Downstream Products

• 125159-24-2 Sodium 4-(3,4-5-trimethoxybenzyl)-1-piperazinecarbodithioate 
• 108463-83-8 3-Isopropyl-1-methyl-3-[2-(4-(4-(3,4,5-trimethoxybenzyl)-1-piperazinyl)butoxy)phenyl)indolin-2-one 
• 220832-41-7 2-chloro-1-(4-(3,4,5-trimethoxybenzyl)piperazin-1-yl)ethanone 
• 1289155-23-2 (S)-2-((1-(benzylsulfonyl)pyrrolidin-3-yl)amino)-1-(4-(3,4,5-trimethoxybenzyl)piperazin-1-yl)ethanone 
• 1589517-79-2 5-(1,2-dithiolan-3-yl)-1-(4-(3,4,5-trimethoxybenzyl)piperazin-1-yl)pentan-1-one 
• 1345843-70-0 2-(4-(3,4,5-trimethoxybenzyl)piperazin-1-yl)acetohydrazide 
• 1345843-87-9 ethyl 2-(4-(3,4,5-trimethoxybenzyl)piperazin-1-yl)acetate 
• 185547-11-9 (4-Hydroxy-phenyl)-[4-(3,4,5-trimethoxy-benzyl)-piperazin-1-yl]-methanone 

Relevant academic research and scientific papers

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.]

Design, Synthesis, and Cytotoxic Evaluation of Certain 7-Chloro-4-(piperazin-1-yl)quinoline Derivatives as VEGFR-II Inhibitors

Signaling pathway inhibition of VEGFR-II is visualized as valuable tool in cancer management. In the current study, the synthesis of novel 1-4-(7-chloroquinolin-4-yl)piperazin-1-yl)-2-(N-substituted-amino)-ethanone derivatives (4a–t) was achieved through the amination of 2-chloro-1-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)ethanone (3) with different secondary amines. The structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR, HRMS, and microanalysis. Compounds 4a–t were subjected to in vitro anticancer screening against human breast cancer (MCF-7) and prostate cancer (PC3) cell lines. The highest cytotoxicty against both cell lines was displayed by 2-(4-(4-bromobenzyl)piperazin-1-yl)-1-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)ethanone (4q), with IC50 values of 6.502 and 11.751 μM against MCF-7 and PC3 cells, respectively, compared with the standard drug doxorubicin (MCF-7: 6.774 μM, PC3: 7.7316 μM). Due to its notable activity toward MCF-7 cells, 4q was further evaluated as VEGFR-II inhibitor, showing an IC50 of 1.38 μM compared to sorafenib (0.33 μM). The docking study proved that 4q has a binding mode akin to that of VEGFR-II inhibitors.

PROCASPASE-ACTIVATING COMPOUNDS AND COMPOSITIONS

The invention provides compounds and compositions useful for the modulation of certain enzymes. The compounds and compositions can induce of cell death, particularly cancer cell death. The invention also provides methods for the synthesis and use of the compounds and compositions, including the use of compounds and compositions in therapy for the treatment of cancer and selective induction of apoptosis in cells.

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.

Flavonoid-related modulators of multidrug resistance: Synthesis, pharmacological activity, and structure-activity relationships

A series of 28 flavonoid derivatives containing a N-benzylpiperazine chain have been synthesized and tested for their ability to modulate multidrug resistance (MDR) in vitro. At 5 μM, most compounds potentiated doxorubicin cytotoxicity on resistant K562/DOX cells. They were also able to increase the intracellular accumulation of JC-1, a fluorescent molecule recently described as a probe of P-glycoprotein-mediated MDR. This suggests that these compounds act, at least in part, by inhibiting P-glycoprotein activity. As in other studies, lipophilicity was shown to influence MDR- modulating activity but was not the only determinant. Diverse di- and trimethoxy substitutions on N-benzyl were examined and found to affect the activity differently. The most active compounds had a 2,3,4- trimethoxybenzylpiperazine chain attached to either a flavone or a flavanone moiety (13, 19, 33, and 37) and were found to be more potent than verapamil.

Therapeutic agent for liver disease and piperazine derivatives

A therapeutic agent for liver disease containing as an active ingredient a piperazine derivative having the formula: STR1 wherein, A represents a phenyl, p-benzoquinonyl or cumarinyl group which may have at least one substituent selected from the group consisting of halogen, alkyl, fluoroalkyl, formyl, alkoxycarbonyl, acyl, hydroxy, alkoxy, acyloxy, glycosyloxy, amino, alkylamino, mercapto, alkylthio and nitro; B represents a single bond or a straight chain alkylene group containing 1-4 carbon atoms which may have at least one substituent selected from the group consisting of alkyl, aryl, aralkyl, hydroxy and oxo; R represents an atom or a group selected from the group consisting of hydrogen, alkali metal, alkaline earth metal, alkyl, cycloalkyl, aralkyl and aryl; and n is 2 or 3, or its pharmaceutically acceptable salt is disclosed.