1445-69-8Relevant articles and documents
Phthalazine-1,4-dione derivatives as non-competitive AMPA receptor antagonists: design, synthesis, anticonvulsant evaluation, ADMET profile and molecular docking
El-Helby, Abdel-Ghany A.,Ayyad, Rezk R. A.,El-Adl, Khaled,Elkady, Hazem
, p. 283 - 298 (2019)
In view of the anticonvulsant activity reported for phthalazine derivatives as non-competitive AMPA receptor antagonists, a new series of phthalazine-1,4-diones (2–12) were designed and synthesized. The neurotoxicity was assessed using rotarod test. The molecular docking was performed for the synthesized compounds to assess their binding affinities toward AMPA receptor as non-competitive antagonists. The molecular modeling data were strongly interrelated to biological screening data. Compounds 8, 7b, 7a, 10 and 3a exhibited the highest binding affinities as non-competitive AMPA receptor antagonists and also showed the highest relative potencies of 1.78, 1.66, 1.60, 1.59 and 1.29, respectively, as anticonvulsants in comparison with diazepam. The most active compounds 8, 7b, 7a, 10 and 3a were further tested against maximal electroshock seizure (MES). Compounds 8 and 7b and 3a showed 100% protection at a dose level of 125?μgm/kg, while compounds 7a and 10 exhibited 83.33% protection at the same dose level. These agents exerted low neurotoxicity and high safety margin in comparison with valproate as a reference drug. Most of our designed compounds exhibited good ADMET profile.
On-water, catalyst-free and room-temperature construction of 2-aryl-1,3,4-oxadiazole derivatives from 1,1-dichloro-2-nitroethene and hydrazides
Zhu, Fengjuan,Zou, Minming,Shao, Xusheng,Li, Zhong
, p. 61752 - 61758 (2015)
2-Aryl-1,3,4-oxadiazoles are important functional molecules in many research fields. A green synthetic method for preparation of 2-aryl-1,3,4-oxadiazoles was developed using hydrazides and highly reactive 1,1-dichloro-2-nitroethene. This eco-friendly protocol featured high yields, purification simplicity, water-based reaction medium, energy efficiency and no addition of catalysts.
Green and efficient synthesis of 1H-indazolo[1,2-b] phthalazine-1,6,11(13H)-triones using ZrO(NO3)2.2H2O as a novel catalyst and theoretical study of synthesized compounds
Saberi Biroon, Shabnam,Shajari, Nahid,Yahyaei, Hooriye
, p. 2433 - 2445 (2020)
The one-pot three-component synthesis for the preparation of 1H-indazolo[1,2-b] phthalazine-1,6,11(13H)-triones through condensation of phthalimide, hydrazine monohydrate, dimedone, and aromatic aldehydes in the presence of a novel catalytic amount of ZrO(NO3)2.2H2O at reflux conditions in water has been reported. Quantum theoretical calculations for the three structures of compounds (5a, 5b, and 5c) were performed using the G3MP2, LC-ωPBE, MP2, and B3LYP methods with the 6-311 + G** basis set. After optimizing the structures, geometric parameters were obtained and experimental measurements were compared with the calculated data. The structures of the products were confirmed by IR, 1H NMR, 13C NMR, and elemental analysis. IR spectra data and 1H NMR and 13C NMR chemical shifts computations of the 1H-indazolo[1,2-b]phthalazine-1,6,11(13H)-trione derivatives in the ground state were calculated. Frontier molecular orbitals, total density of states, thermodynamic parameters, and molecular electrostatic potentials of the title compounds were investigated by theoretical calculations. Molecular properties such as the ionization potential (I), electron affinity (A), chemical hardness (η), electronic chemical potential (μ), and electrophilicity (ω) were investigated for the structures. Consequently, there was an excellent agreement between experimental and theoretical results.
Reaction of α-Acetoxy-N-nitrosopyrrolidine with Deoxyguanosine and DNA
Wang, Mingyao,McIntee, Edward J.,Shi, Yongli,Cheng, Guang,Upadhyaya, Pramod,Villalta, Peter W.,Hecht, Stephen S.
, p. 1428 - 1434 (2001)
We investigated the reactions of α-acetoxy-N-nitrosopyrrolidine (α-acetoxyNPYR) with dGuo and DNA. α-AcetoxyNPYR is a stable precursor to the major proximate carcinogen of NPYR, α-hydroxyNPYR (3). Our goal was to develop appropriate conditions for the analysis of DNA adducts of NPYR formed in vivo. Products of the α-acetoxyNPYR-dGuo reactions were analyzed directly by HPLC or after treatment of the reaction mixtures with NaBH3CN. Products of the α-acetoxyNPYR-DNA reactions were released by enzymatic or neutral thermal hydrolysis of the DNA, then analyzed by HPLC. Alternatively, the DNA was treated with NaBH3CN prior to hydrolysis and HPLC analysis. The reactions of α-acetoxyNPYR with dGuo and DNA were complex. We have identified 13 products of the dGuo reaction - 6 of these were characterized in this reaction for the first time. They were four diastereomers of N2-(3-hydroxybutylidene)-dGuo (20,21), 7-(N-nitrosopyrrolidin-2-yl)Gua (2), and 2-(2-hydroxypyrrolidin-1-yl)deoxyinosine (12). Adducts 20 and 21 were identified by comparison to standards produced in the reaction of 3-hydroxybutanal with dGuo. Adduct 2 was identified by its spectral properties while adduct 12 was characterized by comparison to an independently synthesized standard. With the exception of adduct 2, all products of the dGuo reactions were also observed in the DNA reactions. The major product in both the dGuo and DNA reactions was N2-(tetrahydrofuran-2-yl)dGuo (10), consistent with previous studies. Several other previously identified adducts were also observed in this study. HPLC analysis of reaction mixtures treated with NaBH3CN provided improved conditions for adduct identification, which should be useful for in vivo studies of DNA adduct formation by NPYR.
Heterocyclic synthesis via enaminones: Novel synthesis of (1H)-pyridin-2-one, pyrazolo[1,5-a]pyrimidine and isoxazole derivatives incorporating a N-methylphthalimide and their biological evaluation
Al-Omran, Fatima,El-Khair, Adel A.
, p. 307 - 312 (2005)
Novel synthesis of (1H)-pyridin-2-one, pyrazolo[1,5-a]pyrimidine and isoxazole derivatives incorporating N-methylphthalimide moiety are reported. Reaction of enaminone 2 with malononitrile affords 4. Condensation of 2 with cyanothioacetamide or benzoylacetonitrile affords compounds 6 and 7 respectively. Reaction of 2 with hydrazine hydrate afford 2,3- dihydrophthalazine-1,4-dione (10). Condensation of 2 with hydroxylamine and 3-aminopyrazole derivatives affords compounds 12 and 15a,b respectively. Antimicrobial and antifungal activity were determined for representative compounds and most of them showed moderate activity as antimicrobial agents, while compounds 2 and 7 show strong activity against Aspergillus niger. The structure of the newly synthesized compounds was elucidated by elemental analyses and 1H nmr spectra and some cases by 13C nmr investigation.
An improved procedure for the preparation of aminomethyl polystyrene resin and its use in solid phase (peptide) synthesis
Harris, Paul W.R.,Yang, Sung Hyun,Brimble, Margaret A.
, p. 6024 - 6026 (2011)
2-Aminoethanol was used to successively replace hydrazine in the preparation of aminomethyl polystyrene resin thereby facilitating purification and by-product removal. The syntheses of the polypeptides ACP (65-74) and oxytocin demonstrated that the use of aminomethyl polystyrene resin prepared in this manner was equal to or better than that prepared using the hydrazine method.
One-Pot Four Component Synthesis of 3-Amino-1-(1H-indol-2-yl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine Derivatives Mediated by [DBUH][OAc]
Jeevan Raghavendra,Siddaiah
, p. 1892 - 1898 (2018)
One-pot, four component, green, and efficient synthesis of 3-amino-1-(5-nitro-1H-indol-2-yl)-5,10-dioxo-5,10-dihydro-1H-pyrazolo[1,2-b]phthalazine derivatives by reaction of phthalic anhydride with hydrazine hydrate, 5-nitro-1H-indole-3-carboxaldehyde–indole-3-carboxaldehydes and malononitrile–ethyl cyanoacetate in the presence of [DBUH][OAc] at 60–65°C is developed. The method is characterized by short reaction time, high yields, and purity of products formed.
A Peptide Backbone Stapling Strategy Enabled by the Multicomponent Incorporation of Amide N-Substituents
Ricardo, Manuel G.,Marrrero, Javiel F.,Valdés, Oscar,Rivera, Daniel G.,Wessjohann, Ludger A.
, p. 769 - 774 (2019)
The multicomponent backbone N-modification of peptides on solid-phase is presented as a powerful and general method to enable peptide stapling at the backbone instead of the side chains. This work shows that a variety of functionalized N-substituents suitable for backbone stapling can be readily introduced by means of on-resin Ugi multicomponent reactions conducted during solid-phase peptide synthesis. Diverse macrocyclization chemistries were implemented with such backbone N-substituents, including the ring-closing metathesis, lactamization, and thiol alkylation. The backbone N-modification method was also applied to the synthesis of α-helical peptides by linking N-substituents to the peptide N-terminus, thus featuring hydrogen-bond surrogate structures. Overall, the strategy proves useful for peptide backbone macrocyclization approaches that show promise in peptide drug discovery.
Blue highly fluorescent boron difluoride complexes based on phthalazine-pyridine
Vuong, Thi Minh Ha,Weimmerskirch-Aubatin, Jennifer,Lohier, Jean-Fran?ois,Bar, Nathalie,Boudin, Sophie,Labbé, Christophe,Gourbilleau, Fabrice,Nguyen, Hien,Dang, Tung Thanh,Villemin, Didier
, p. 6070 - 6076 (2016)
Three new boron difluoride complexes based on phthalazine-pyridine, denoted (6), (7) and (8), have been synthesized and their photophysical and electrochemical properties have been studied. Solutions of these new BF2-complexes exhibit an intense blue fluorescence under UV light at low concentrations. Fluorescence quantum yields (QYs) have been determined by photoluminescence (PL) spectroscopy and decay times (τ) by semi-empirical methods. QYs of (6), (7) and (8) vary from 25% to 79%. HOMO and LUMO energy levels have been estimated by cyclic voltammetry and PL spectroscopy. The HOMO and LUMO energy levels, at ～-5.3 eV and ～-2.3 eV, respectively, make these new complexes interesting candidates as blue emitters in OLED applications.
Single-particle and ensemble diffusivitiesa-test of ergodicity
Feil, Florian,Naumov, Sergej,Michaelis, Jens,Valiullin, Rustem,Enke, Dirk,Kaerger, Joerg,Braeuchle, Christoph
, p. 1152 - 1155 (2012)
To prove the ergodic theorem experimentally the diffusivities of guest molecules inside a nanostructured porous glass were measured by using two conceptually different approaches under identical conditions. The data obtained through the direct observation of dye-molecule diffusion by single-molecule tracking experiments (red circles) was in perfect agreement with the ensemble value obtained in pulsed-field gradient NMR experiments (black squares). Copyright
