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6531-38-0Relevant academic research and scientific papers
Bis-aminals of linear tetraamines: Kinetic and thermodynamic aspects of the condensation reaction
Chuburu, Francoise,Tripier, Raphael,Le Baccon, Michel,Handel, Henri
, p. 1050 - 1055 (2003)
The kinetic and thermodynamic aspects of the condensation reaction of dicarbonyl compounds with linear tetraamines were examined in the light of identification of intermediates and DFT calculations. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, German
Metal ion substitution and aldehyde exchange for CuII4 aggregates from two types of piperazine-based Schiff base ligands: Synthesis, X-ray structures, magnetic studies and theoretical validation
Basak, Dipmalya,Ray, Debashis
, (2020)
Two new tetranuclear CuII complexes [Cu4(L2)2(μ2-OH)2(H2O)2]·(ClO4)2·DMF·2H2O (1) and [Cu4(L3)2(μ2-OH)2(H2O)2]·(ClO4)2·DMF·H2O (2) have been synthesized containing piperazine based Schiff base ligands H2L2 (asymmetric) and H2L3 (symmetric). H2L2 contains one o-vanillin and a salicylaldehyde unit while H2L3 has two o-vanillin units. An interesting synthetic methodology involving transition metal ion induced aldehyde exchange reaction between two Schiff base ligands has been explored for the synthesis of H2L2 and H2L3. While the latter can be obtained by direct condensation of the respective amine and aldehyde, the former can only be synthesized by this procedure developed. Both 1 and 2 contain a piperazine ring bridging two CuII centers in chair conformation in the rare axial-equatorial mode of coordination. Two piperazine bridged Cu2 moieties are further connected via two hydroxido and two phenoxido bridges. Of the two Ophenoxido–Cu bonds one is short (basal) and the other is long (apical) while the hydroxido O bridges the two CuII centers symmetrically in basal–basal manner giving rise to a unique [Cu2O2] moiety where, of the four bonds linking the metals, three are basal (short) and one axial (long). Magnetic studies reveal weak antiferromagnetic interactions across the two piperazine bridges with an average exchange constant value of ?4.007 cm?1 and ?4.507 cm?1 for 1 and 2 respectively. The antiferromagnetic exchanges across the phenoxido–hydroxido bridges were found to be stronger with the average value being ?43.036 cm?1 for 1 and ?38.031 cm?1 for 2. Computational studies further support the experimental findings and the spin density plots in the HS configuration reveal that the exchange across the piperazine bridge takes place via through space mechanism. The spin density analysis in the HS and BS configurations also reveal that the exchange interaction is propagated mainly through the hydroxido bridge. The unsymmetrical nature of H2L2 leads to greater spin density at the hydroxido bridge in 1 leading to slightly stronger exchange interaction.
Syntheses and crystal structures of Ni(II) complexes with pyridine-based macrocyclic ligands
Císa?ová, Ivana,Draho?, Bohuslav,Zahradníková, Eva
supporting information, (2021/11/17)
Three pyridine-based macrocyclic ligands, two containing one pyridine pendant arm (L1 and L2) and one containing piperazine rings in the macrocyclic scaffold (L3), with an increasing size of the macrocycle from 12-, 14- to 30-membered ring for L1–L3 were synthesized and characterized. A series of Ni(II) complexes with all these ligands, with molecular formulas [NiL1(CH3OH)](ClO4)2 (1), [NiL2(CH3CN)](ClO4)2 (2), and [Ni2L3(DMF)2(CH3CN)2](ClO4)4 (3) (DMF = N,N–dimethylformamide), was prepared and thoroughly characterized. Single crystal X-ray structural analysis confirmed that all the complexes have a coordination number of six and their geometries are close to octahedral. In the case of the mononuclear complexes 1 and 2, all the nitrogen atoms of the macrocycle are coordinated, however, in the dinuclear complex 3 with the piperazine-based ligand L3, two nitrogen donor atoms (of the total number of ten) are uncoordinated. The first coordination spheres of all the complexes are completed by solvent molecules. The values of effective magnetic moments, determined by the Evans method in solution, are 3.12, 3.19 and 4.36 μB for complexes 1, 2 and 3, respectively, which correspond well to the theoretical spin-only values.
CENTRALLY ACTIVE AND ORALLY BIOAVAILABLE UNCHARGED BISOXIME ANTIDOTES FOR ORGANOPHOSPHATE POISONING AND METHODS FOR MAKING AND USING THEM
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Page/Page column 38; 41; 45-46, (2020/12/07)
In alternative embodiments, provided are uncharged bis-oxime antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). In alternative embodiments, provided are pumps, devices, subcutaneous infusion devices, continuous subcutaneous infusion devices, infusion pens, needles, reservoirs, ampoules, a vial, a syringe, a cartridge, a disposable pen or jet injector, a prefilled pen or a syringe or a cartridge, a cartridge or a disposable pen or jet injector, a two chambered or multi-chambered pump, a syringe, a cartridge or a pen or a jet injector, comprising a compound as provided herein.
The effect of the structure of derivatives of nitrogen-containing heterocycles on their anti-influenza activity
Gridina, Tatyana L.,Fedchuk, Alla S.,Basok, Stephan S.,Artemenko, Anatoliy G.,Ognichenko, Liudmila N.,Shitikova, Larisa I.,Lutsyuk, Anatolii F.,Gruzevskii, Aleksandr A.,Kuz’min, Victor E.
, p. 455 - 462 (2019/06/20)
[Figure not available: see fulltext.] An adequate QSAR model based on the simplex representation of the molecular structure was built in order to optimize the search for new anti-influenza agents. Structural interpretation of the model allowed us to identify molecular fragments that determine the activity of compounds against human influenza viruses. Further virtual screening and targeted synthesis allowed us to select a group of potentially effective compounds, three of which, derivatives of piperidine and isoindoline, turned out to be the most promising.
COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS
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Page/Page column 219-220, (2010/08/04)
The present disclosure is directed to corn- pounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders. The methods generally comprise administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that is designed to be substantially active in the gastrointestinal (GI) tract to inhibit NHE-mediated antiport of sodium ions and hydrogen ions therein. More particularly, the method comprises administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that inhibits NHE-3, -2 and/ or -8 mediated antiport of sodium and/or hydrogen ions in the GI tract and is designed to be substantially impermeable to the layer of epithelial cells, or more specifically the epithelium of the GI tract. As a result of the compound being substantially impermeable, it is not absorbed and is thus essentially systemically non-bioavailable, so as to limit the exposure of other internal organs (e.g., liver, heart, brain, etc.) thereto. The present disclosure is still further directed to a method wherein a mammal is administered such a compound with a fluid-absorbing polymer, such that the combination acts as described above and further provides the ability to sequester fluid and/or salt present in the GI tract
Structure and dimensionality of coordination complexes correlated to piperazine conformation: From discrete [CuII2] and [CuII4] complexes to a μ1,3-N 3- bridged [CuII2]n chain
Paital, Alok Ranjan,Mandal, Debashree,Huang, Xiaoying,Li, Jing,Aromi, Guillem,Ray, Debashis
supporting information; scheme or table, p. 1352 - 1362 (2009/06/05)
Three different types of copper(ii) complexes have been studied of the hexadentate Schiff base ligand N,N′-bis[2-{(salicylidenimine)amino}ethyl] piperazine (H2L) having the piperazine backbone in the chair form and axial-axial (a,a) N-atom lone pairs in the free state. The structure of the products is influenced by the reaction conditions and by the exogenous ligands, affecting the conformation of the piperazine moiety (primary structure) and the topology and nuclearity of the resulting complexes (secondary structure). In [Cu2L(DMF)2]X2 (X = ClO4 -, 1a; NO3-, 1b), the lone-pairs of chair-piperazine adopt the equatorial-equatorial (e,e) conformation. In the presence of NEt3 and NaN3, two types of [Cu II4] complexes [Cu4(L)2(OH) 2(H2O)2]X2·nH2O (X = ClO4-, n = 1, 2a; X = NO3-, n = 4, 2b) and [Cu4(L)2(N3)2(H 2O)2]X2·H2O (X = ClO 4-, 3a; NO3-, 3b) are obtained where four copper(ii) ions are bridged by two hexadentate μ3-piperazine ligands, this time in chair-e,a conformation, and by two OH and N3 groups. In CH3CN, reactions of 1, 2 or 3 with NaN3 always produce the double end-to-end azido bridged 1D polymer [Cu2L(N 3)2]n (4) having a chair-e,e piperazine backbone. All studied conformations of the piperazine bridge mediate antiferromagnetic interactions between the Cu(ii) ions, as revealed by bulk magnetization measurements. The striking difference in intensity of the coupling through trans-e,e piperazine observed for complexes 1a and 4 might be due to complementarily effects between the ligands involved.
Molecular modelling studies, synthesis and biological activity of a series of novel bisnaphthalimides and their development as new DNA topoisomerase II inhibitors
Filosa, Rosanna,Peduto, Antonella,Di Micco, Simone,Caprariis, Paolo de,Festa, Michela,Petrella, Antonello,Capranico, Giovanni,Bifulco, Giuseppe
experimental part, p. 13 - 24 (2011/02/25)
A series of bisnaphthalimide derivatives were synthesized and evaluated for growth-inhibitory property against HT-29 human colon carcinoma. The N,N′-bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin- 2-yl)]propane-2-ethanediamine (9) and the N,N′-Bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin- 2-yl)]butylaminoethyl]-2-propanediamine (12) derivatives emerged as the most potent compounds of this series. Molecular modelling studies indicated that the high potency of 12, the most cytotoxic compound of the whole series, could be due to larger number of intermolecular interactions and to the best position of the naphthalimido rings, which favours π-π stacking interactions with purine and pyrimidine bases in the DNA active site. Moreover, 12 was designed as a DNA topoisomerase II poison and biochemical studies showed its effect on human DNA topoisomerase II. We then selected the compounds with a significant cytotoxicity for apoptosis assay. Derivative 9 was able to induce significantly apoptosis (40%) at 0.1 μM concentration, and we demonstrated that the effect on apoptosis in HT-29 cells is mediated by caspases activation.
Novel combi-molecules having EGFR and DNA targeting properties
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Page/Page column 14; 24, (2010/02/15)
A series of new chemical agents that demonstrate anti-tumor activity are described. The new chemical agents combine two major mechanisms of anti-tumor action. In an embodiment, the agents are capable of both inhibiting EGFR and damaging DNA while also, upon degradation, degrading to an inhibitor of EGFR and to an agent capable of damaging DNA. Moreover, a novel series of molecules capable of releasing two moles of EGFR inhibitor and a potent bi-functional alkylating agent are also described.
Bisintercalating Threading Diacridines: Relationships between DNA Binding, Cytotoxicity, and Cell Cycle Arrest
Wakelin, Laurence P. G.,Bu, Xianyong,Eleftheriou, Alexandra,Parmar, Alpesh,Hayek, Charbel,Stewart, Bernard W.
, p. 5790 - 5802 (2007/10/03)
We have synthesized a series of bis(9-aminoacridine-4-carboxamides) linked via the 9-position with neutral flexible alkyl chains, charged flexible polyamine chains, and a semirigid charged piperazine-containing chain. The carboxamide side chains comprise N,N-dimethylaminoethyl and ethylmorpholino groups. The compounds are designed to bisintercalate into DNA by a threading mode, in which the side chains are intended to form hydrogen-bonding contacts with the O6/N7 atoms of guanine in the major groove, and the linkers are intended to lie in the minor groove. By this means, we anticipate that they will dissociate slowly from DNA, and be cytotoxic as a consequence of template inhibition of transcription. The dimers remove and reverse the supercoiling of closed circular DNA with helix unwinding angles ranging from 26° to 46°, confirming bifunctional intercalation in all cases, and the DNA complexes of representative members dissociate many orders of magnitude more slowly than simple aminoacridines. Cytotoxicity for human leukemic CCRF-CEM cells was determined, the most active agents having IC50 values of 35-50 nM in a range extending over 20-fold, with neither the dimethylaminoethyl nor the ethylmorpholino series being intrinsically more toxic. In common with established transcription inhibitors, the morpholino series, with one exception, have no effect on cell cycle distribution in randomly dividing CCRF-CEM populations. By contrast, the dimethylaminoethyl series, with two exceptions, cause G2/M arrest in the manner of topoisomerase poisons, consistent with possible involvement of topoisomerases in their mode of action. Thus, the cellular response to these bisintercalating threading agents is complex and appears to be determined by both their side chain and linker structures. There are no simple relationships between structure, cytotoxicity, and cell cycle arrest, and the origins of this complexity are unclear given that the compounds bind to DNA by a common mechanism.
