5430-78-4

Usage

Uses

Used in Pharmaceutical and Agrochemical Synthesis:
Piperazine-1,4-diacetic acid is used as a building block for the synthesis of various pharmaceuticals and agrochemicals. Its unique structure and functional groups contribute to the development of new compounds with therapeutic or pesticidal properties.
Used in Chelating Applications:
As a chelating agent, piperazine-1,4-diacetic acid is used for binding metal ions. This application is valuable in various industrial processes, including the formulation of corrosion inhibitors to protect materials from degradation.
Used in Environmental Applications:
Piperazine-1,4-diacetic acid is used in the treatment of wastewater due to its ability to chelate metal ions, which helps in the removal of contaminants and the purification of water.
Used in Industrial Applications:
piperazine-1,4-diacetic acid is also utilized in industrial settings for the development of corrosion inhibitors, where its chelating properties aid in the prevention of metal corrosion, thus extending the lifespan of materials and structures.

InChI:InChI=1/C8H14N2O4/c11-7(12)5-9-1-2-10(4-3-9)6-8(13)14/h1-6H2,(H,11,12)(H,13,14)

Upstream product

• 40479-50-3 2,2′-piperazine-1,4-diyldiacetamide 
• 110-85-0 piperazine 
• 79-11-8 chloroacetic acid 
• 79-08-3 bromoacetic acid 
• 7709-77-5 dimethyl 2,2′-(piperazine-1,4-diyl)diacetate 
• 40479-62-7 sodium 2,2'-(piperazine-1,4-diyl)diacetate 

Downstream Products

• 1354578-40-7 C₃₅H₄₂N₆O₇S 

Relevant academic research and scientific papers

Structure and total synthesis of aspernigerin: A novel cytotoxic endophyte metabolite

Aspernigerin (1), a novel cytotoxic alkaloid consisting of an unprecedented structural framework has been isolated from the extract of a culture of Aspergillus niger IFB-E003, an endophyte in Cyndon dactylon. Its structure was elucidated on the basis of comprehensive NMR spectral analysis and confirmed by single-crystal X-ray analysis. Aspernigerin (1) has been shown to be cytotoxic to the tumor cell lines nasopharynyeal epidermoid KB, cervical carcinoma Hela, and colorectal carcinoma SW1116 with corresponding IC50 values of 22, 46, and 35 UM, respectively. A feasible total synthetic route for aspernigerin (1) has been established for further pharmacological research.

NOTA analogue: A first dithiocarbamate inhibitor of metallo-β-lactamases

The emergence of antibiotic drug (like carbapenem) resistance is being a global crisis. Among those resistance factors of the β-lactam antibiotics, the metallo-β-lactamases (MBLs) is one of the most important reasons. In this paper, a series of cyclic dithiocarbamate compounds were synthesized and their inhibition activities against MBLs were initially tested combined with meropenem (MEM) by in vitro antibacterial efficacy tests. Sodium 1,4,7-triazonane-1,4,7-tris(carboxylodithioate) (compound 5) was identified as the most active molecule to restore the activity of MEM. Further anti-bacterial effectiveness assessment, compound 5 restored the activity of MEM against Escherichia coli, Citrobacter freundii, Proteus mirabilis and Klebsiella pneumonia, which carried resistance genes of blaNDM-1. The compound 5 was non-hemolytic, even at a concentration of 1000 μg/mL. This compound was low toxic toward mammalian cells, which was confirmed by fluorescence microscopy image and the inhibition rate of HeLa cells. The Ki value of compounds 5 against NDM-1 MBL was 5.63 ± 1.27 μM. Zinc ion sensitivity experiments showed that the inhibitory effect of compound 5 as a MBLs inhibitor was influenced by zinc ion. The results of the bactericidal kinetics displayed that compound 5 as an adjuvant assisted MEM to kill all bacteria. These data validated that this NOTA dithiocarbamate analogue is a good inhibitor of MBLs.

Optimization of Cyclic Plasmin Inhibitors: From Benzamidines to Benzylamines

New macrocyclic plasmin inhibitors based on our previously optimized P2-P3 core segment have been developed. In the first series, the P4 residue was modified, whereas the 4-amidinobenzylamide in P1 position was maintained. The originally used P4 benzylsulfonyl residue could be replaced by various sulfonyl- or urethane-like protecting groups. In the second series, the P1 benzamidine was modified and a strong potency and excellent selectivity was retained by incorporation of p-xylenediamine. Several analogues inhibit plasmin in the subnanomolar range, and their potency against related trypsin-like serine proteases including trypsin itself could be further reduced. Selected derivatives have been tested in a plasma fibrinolysis assay and are more effective than the reference inhibitor aprotinin. The crystal structure of one inhibitor was determined in complex with trypsin. The binding mode reveals a sterical clash of the inhibitor's linker segment with the 99-hairpin loop of trypsin, which is absent in plasmin.

A new strategy for the development of highly potent and selective plasmin inhibitors

A new structure-based strategy for the design of potent and selective plasmin inhibitors was developed. These compounds could be prepared by cyclizations between the P3 and P2 amino acid residues of substrate-analogue inhibitors using metathesis or a copper-catalyzed azide alkyne cycloaddition in combination with standard peptide couplings. The most potent bis-triazole derivative 10 inhibits plasmin and plasma kallikrein with Ki of 0.77 and 2.4 nM, respectively, whereas it has poor activity against the related trypsin-like serine proteases thrombin, factor Xa, or activated protein C. Modeling experiments revealed that inhibitor 10 adopts a compact and rigid structure that fits well into the relatively open active site of plasmin and plasma kallikrein, while it is rejected from sterically demanding residues present in loops of the other enzymes. These results from modeling confirm the selectivity profile found for inhibitor 10 in enzyme kinetic studies. Such compounds might be useful lead structures for the development of new antifibrinolytic drugs for use in cardiac surgery with cardiopulmonary bypass or organ transplantations to reduce bleeding complications.

SERINE PROTEASE INHIBITORS

The invention provides methods of making and using compounds of the formula shown, which are inhibitors of human plasmin and plasma kallikrein. (Formula I) The compounds are useful for the prevention of blood loss, and as components of fibrin adhesives.

Synthesis and in vitro enzyme hydrolysis of trioxadiaza- and tetraoxadiaza-crown ether-based complexing agents with disposable ester pendant arms

New disposable ester derivatives of the complexing agents N,N′-bis(carboxymethyl)piperazine, -homopiperazine, -1,7-diaza-15-crown-5 and -1,10-diaza-18-crown-6 were synthesized with a variety of synthetic methods and fully characterized. Hydrolytic properties of the pendant arms were studied under different pH conditions as well as in the presence and absence of porcine liver esterase enzyme and approximate hydrolysis half lives were determined by 1H NMR technique. In vitro studies on pig liver cell homogenates and living thin chicken liver slices proved that the selected double ester 4b can penetrate liver tissues spontaneously, liberate the free complexing agent N,N′-bis(carboxymethyl)-18-ane-N2O4 (ODDA) inside the cells and are potentially capable of removing lead and other toxic metal ions from the liver. Georg Thieme Verlag Stuttgart.

POLYBASIC AMINES. I. SYNTHESIS OF N-CARBOXYMETHYL- AND N-(β-CARBOXYETHYL)-N-(β-AMINOETHYL)PIPERAZINES

The hydrolysis of N-(β-cyanoethyl)-N'-(β-salicylideneaminomethyl)piperzine in the presence of hydrochloric acid leads to the formation of N-(β-carboxyethyl)-N'-(β-aminoethyl)piperazine, from which N-(β-carboxyethyl)-N'-(biscarboxymethyl-aminoethyl)piperazine is produced by the action of monochloroacetic acid.Under analogous conditions the hydrolysis of N-carboxymethyl-N'-(β-salicylideneaminoethyl)piperazine with concentrated hydrochloric acid followed by cyanoethylation of the product and hydrolysis gave N-carboxymethyl-N'-(di-β-carboxyethylaminoethyl)piperazine.

A THERMOMETRIC TITRIMETRIC STUDY OF THE COMPLEXATION OF ALKALINE-EARTH METALS BY MACROCYCLIC POLY(AMINOCARBOXYLIC) ACIDS

Thermometric titrimetry has been employed to determine K, ΔH and ΔS data for the complexation reaction in aqueous solution of 1,4-piperazine-N,N'-diacetic acid, 1,5-diazacyclooctane-N,N'-diacetic acid, 1-oxa-4,7-diazacyclononane-N,N'-diacetic acid, 4-oxa-1,7-diazacyclodecane-N,N'-diacetic acid and 1,11-dioxa-4,8-diazacyclotridecane-N,N'-diacetic acid with alkaline earth metal cations.Factors influencing the thermodynamic stability of these complexes are discussed.