6820-93-5

Usage

Molar mass

246.306 g/mol

Physical form

White to off-white powder

Solubility

Sparingly soluble in water

Uses

Research and development for pharmaceutical and chemical applications; building block in the synthesis of biologically active compounds

Value in drug discovery

Potentially valuable tool due to its structure and properties

Upstream product

• 140-31-8 aminoethylpiperazine 
• 85-44-9 phthalic anhydride 

Downstream Products

• 4553-20-2 2‐((2‐4‐benzylpiperazinil‐1‐yl)ethyl)isoindoline‐1,3‐dione 
• 4553-21-3 2-(4-benzylpiperazin-1-yl)-ethylamine 

Relevant academic research and scientific papers

Donepezil structure-based hybrids as potential multifunctional anti-Alzheimer’s drug candidates

A new series of multifunctional hybrids, based on the structure of the donepezil (DNP) drug, have been developed and evaluated as potential anti Alzheimer’s disease (AD) agents. The rationale of this study was the conjugation of a benzylpiperidine/benzylpiperazine moiety with derivatives of bioactive heterocyclics (benzimidazole or benzofuran), to mimic the main structure of DNP and to endow the hybrids with additional relevant properties such as inhibition of amyloid beta (Aβ) peptide aggregation, antioxidant activity and metal chelation. Overall, they showed good activity for AChE inhibition (IC50=4.0–30.0?μΜ) and moderate ability for inhibition of Aβ1–42 self-mediated aggregation. The hybrids containing chelating groups showed improvement in the inhibition of Cu-induced Aβ42 aggregation and the antioxidant capacity. Moreover, neuroprotective effects of these compounds were evidenced in neuroblastoma cells after Aβ1–42 induced toxicity. Structure–activity relationship allowed the identification of some promising compounds and the main determinant structural features for the targeted properties.

Design, synthesis and molecular docking studies of novel piperazine metal complexes as potential antibacterial candidate against MRSA

In the present study, a series of novel metal piperazine carboxamide analogues 5(a-l) were synthesized and amply characterized by different spectral techniques viz, LC-MS, 1H-NMR, 13C-NMR, and FT-IR. Among these, 5e analogue of piperazine complex showed potent biocidal activity. Further, 5e metal complexes of piperazine copper (II), cobalt (II), zinc (II) and nickel (II) were synthesized and characterized by LC-MS and FT-IR and revealed data showed respectable blends of metal complexes. All the metal complexes of 5e analogue were screened for antibacterial activity. The 5e with copper metal complex showed an excellent antibacterial activity (5Cu). The minimum inhibitory concentration of 5e and copper complex (5cu) against MRSA were found to be 30±0.15 and 20±0.12 μg/mL and 14.5±0.04 and 15±0.08 mm of zone of inhibition respectively compared to drug streptomycin and bacitracin (10 μg/mL). The anti-bacterial potency of the newly synthesized template was also validated by membrane damaging study. The molecular docking study was performed to understand the molecular interaction and binding mode of the compounds on active site of 3VMT and 6FTB protein of MRSA. An in silico docking assisted data strongly correlated to the experimental approach of antibacterial activity against MRSA. The biocompatibility of 5e and 5cu was established and that indicated good compatible at the hemostatic level. The 5e and 5cu analogues were also evaluated for toxicity against L6 cell lines. The eventual outcome of this study shows, the synthesized 5cu complex template can be used for further development to eradicate the MRSA infection.

Synthesis, characterization and X-ray crystal structure of potentially N6O2 coordinating macroacyclic Schiff base ligands and their Mn(II), Zn(II) and Cd(II) complexes; cytotoxic, antibacterial properties and competitive 7Li NMR studies

In this work, two new symmetrical, potentially N6O2 coordinating, macroacyclic Schiff base ligands (H2L1 and H2L2) were derived from the condensation of a newly synthesized polyamine, 2,2′-(ethane-1,2-diylbis(piperazine-4,1-diyl))bis(ethan-1-amine) (A), with 2-hydroxybenzaldehyde and 2-hydroxy-3-methoxybenzaldhyde respectively. Six macroacylic Schiff base complexes were prepared by direct reaction of H2L1 or H2L2 with Mn(II), Zn(II) or Cd(II) metal ions in equimolar ratios. The products were characterized by several physicochemical measurements. As well, the crystal structure of H2L1 was confirmed by a single crystal X-ray structural analysis. Competitive 7Li NMR experiments were used to probe the complexation of Mn2+, Zn2+ and Cd2+ ions with (H2L1) and (H2L2) in both acetonitrile and methanol. The stabilities of the final complexes were found to be in the order M–(H2L1) > M–(H2L2) and Cd2+ > Zn2+ > Mn2+. The cytotoxic and antibacterial properties of these complexes were also investigated.

Synthesis, characterization, in vitro cytotoxicity activity, and molecular docking studies of mononuclear and binuclear Macroacyclic Schiff base complexes

A number of binuclear and mononuclear macroacyclic Schiff base complexes containing piperazine moieties were synthesized. The binuclear complexes (M2L1) characterized by elemental analysis, IR and, also Ni(II) complex by a X-ray single crystal structural analysis. In this case, X-ray showed that each nickel atom is in a mer-N3O3 octahedral coordination environment. Moreover, mononuclear macroacyclic Schiff base complexes (ML2 and ML3) were prepared based on the condensation reaction of an amine containing piperazine moiety and 2-hydroxy banzaldehyde or formyl pyridine in 1:2 mol ratio in the presence of Ni(II), Cu(II), and Co(II) ions. All of compounds were characterized by elemental analyses, FT-IR, mass spectrometry and ligands characterized by 1H and 13C NMR spectroscopy. The cytotoxicity of the complexes was evaluated against two different cancer cell lines including MCF-7 (breast) and A549 (lung) adenocarcinoma cells. In general, binuclear complexes, possesses a higher cytotoxic effect against the tested cells than the other complexes. In addition, the biological assessment of complexes have been examined via molecular docking. As an interesting results, the binuclear complexes have the highest inhibition effect against cytotoxic receptors.

New approach to address antibiotic resistance: Miss loading of functional membrane microdomains (FMM) of methicillin-resistant Staphylococcus aureus (MRSA)

The synthesized potent piperazine analog ChDiPiCa was characterised by various spectroscopic techniques and for the first time evaluated functional membrane microdomain (FMM) disassembly in methicillin-resistant Staphylococcus aureus (MRSA). The ChDiPiCa showed excellent in vitro biocidal activity against MRSA at 26 μg/mL compared to the antibiotic streptomycin and bacitracin 14 μg/mL and 13 μg/mL at 10 μg concentration respectively. The membrane damaging property was confirmed by the SEM analysis. Further, we addressed the new approach for the first time to overcome antibiotic resistance of MRSA through membrane microdomain miss loading to lipids. By which, the ChDiPiCa confirms the significant activity in miss loading of FMM of MRSA which is validated by the fatty acid profile and lipid analysis. The result shows that, altered saturated (Lauric acid and Myristic acid), mono unsaturated (Oleic acid), and poly unsaturated (Linoleic acid and Linolenic acid) fatty acids and hypothesises, altered the membrane functional lipids. For the better understanding of miss loading of FMM by the ChDiPiCa, the in-silico molecular docking studies was analyzed and confirmed the predicted role. This suggests the way to develop ChDiPiCa in medicinal chemistry as anti-MRSA candidates and also this report opens up new window to treat microbial pathogens and infections.

Novel donepezil?arylsulfonamide hybrids as multitarget-directed ligands for potential treatment of Alzheimer?s disease

Alzheimer’s disease (AD) is one of the most devastating neurodegenerative disorders, characterized by multiple pathological features. Therefore, multi-target drug discovery has been one of the most active fields searching for new effective anti-AD therapies. Herein, a series of hybrid compounds are reported which were designed and developed by combining an aryl-sulfonamide function with a benzyl-piperidine moiety, the pharmacophore of donepezil (a current anti-AD acetylcholinesterase AChE inhibitor drug) or its benzyl-piperazine analogue. The in vitro results indicate that some of these hybrids achieve optimized activity towards two main AD targets, by displaying excellent AChE inhibitory potencies, as well as the capability to prevent amyloid-β (Aβ) aggregation. Some of these hybrids also prevented Aβ-induced cell toxicity. Significantly, drug-like properties were predicted, including for blood-brain permeability. Compound 9 emerged as a promising multi-target lead compound (AChE inhibition (IC50 1.6 μM); Aβ aggregation inhibition 60.7%). Overall, this family of hybrids is worthy of further exploration, due to the wide biological activity of sulfonamides.

Deep Eutectic Solvents as Effective Reaction Media for the Synthesis of 2‐Hydroxyphenylbenzimidazole-based Scaffolds en Route to Donepezil‐Like Compounds

An unsubstituted 2‐hydroxyphenylbenzimidazole has recently been included as a scaffold in a series of hybrids (including the hit compound PZ1) based on the framework of the acetylcholinesterase (AChE) inhibitor Donepezil, which is a new promising multi‐target ligand in Alzheimer’s disease (AD) treatment. Building upon these findings, we have now designed and completed the whole synthesis of PZ1 in the so‐called deep eutectic solvents (DESs), which have emerged as an unconventional class of bio‐renewable reaction media in green synthesis. Under optimized reaction conditions, the preparation of a series of 2‐hydroxyphenylbenzimidazole‐based nuclei has also been perfected in DESs, and comparison with other routes which employ toxic and volatile organic solvents (VOCs) provided. The functionalization of the aromatic ring can have implications on some important biological properties of the described derivatives and will be the subject of future studies of structure‐activity relationships (SARs).

REACTIONS OF N-(β-AMINOETHYL)PIPERAZINE AND ITS DERIVATIVES

The alkylation, cyanoethylation, and heterocyclization reactions of N-(β-aminoethyl)piperazine and its derivatives, dicarboxylic acid imides, have been investigated.A new method has been proposed for the synthesis of 1,4-diazabicyclooctane via pyrolytic cleavage of N,N'-bisethylenediamine.