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The importance of triazole scaffold in the development of anticonvulsant agents

Epilepsy is one of the most important neurological disorders with high prevalence worldwide. Many epileptic patients are not completely treated with available drugs and need multiple therapies. Also, many antiepileptic drugs have shown unwanted side effects and drug interactions. Therefore there are continuing interests to find new anticonvulsant drugs. Triazole ring has been found in the structure of many compounds with diverse biological effects. Due to the success of several triazole-containing drugs that entered the pharmaceutical market as CNS-active drugs, this class of heterocyclic compounds has great importance for discovery and development of new anticonvulsant drugs. In this article, we have tried to summarize the latest efforts which have been made in the design and development of triazole-derived anticonvulsant agents.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N47 – PubChem

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Design, synthesis, characterization, QSAR, docking, anti-inflammatory and analgesic evaluation of some new phthalazinediones

Background: phthalazine derivatives were reported to possess anticonvulsant, cardiotonic, antibacterial, analgesic, anti-inflammatory, and anti-microbial activity. In the current study, we applied the QSAR for prediction of newly phthalazinediones incorporating thioamide moiety aiming to reach a more potent anti-inflammatory and Analgesic agent. Methods: Phthalazinediones 10-15 have been synthesized through condensation of dibenzobarallene 3 with thiosemicarbazides 4-8. One equation was predicted using quantitative structure activity relationship (QSAR) and regression analysis for the anti-inflammatory activity with a regression correlation (R) close to unity. The docking studies were performed to investigate the biological trends of the organic compounds (thiol form) against cyclooxygenas- 2 enzyme, which is a responsible inflammation mediator by using Molgro Virtual Docker (MVD) software. The anti-inflammatory activity and analgesic effect of the thioamides 10-15 were determined by collagen II-adjuvant induced paw edema test in rats. Results: Compounds 10, 11, 12, and 14, exhibited promising anti-inflammatory activity. Furthermore, in the pain scoring, compounds 10, 11 and 12 were found to be more effective than piroxicam and the order of the analgesic effect of the investigated compounds is as followed 14 > 12 > 10 > 11 > 15. Conclusion: It is clear from the foregoing that the compound 14 is a promising compound if future pharmacological detailed studies. This is consistent with what has been predictable equation 1 in this study.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N403 – PubChem

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Synthesis and antitumor activity evaluation of 3,6-substituted-1,2,4-triazolo[3,4-a]phthalazine derivatives

With the aim of obtaining potential antitumor candidates with more efficiency and more economic value. A series of 3,6-substituted-1,2,4-triazolo[3,4-a]phthalazine derivatives were synthesized. The target products were obtained via cyclization, chlorination, substitution, cyclization, substituted with phthalic anhydride used as the starting material. The structures of target products are confirmed by 1H NMR, I3C NMR, HRMS. A series of 3,6-substituted-1,2,4-triazolo[3,4-a] phthalazine derivatives was evaluated for anticancer activity on four human cancer cell lines including EC-9706, HeLa and MCF-7 by MTT assay. Among them, compound 5d was more cytotoxic against EC-9706 and HeLa cell lines, with IC50 values ranging from 3.9 to 4.5 mumol?L-1, which are superior or comparable to 5-Fuorouracil. Flow cytometry analysis indicated that compound 5d induced the cellular early apoptosis and cell cycle arrest in G2/M phase in EC-9706.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N468 – PubChem

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In silico molecular docking studies of new potential 4-phthalazinyl-hydrazones on selected Trypanosoma cruzi and Leishmania enzyme targets

Recently, a series of 4-phthalazinyl-hydrazones under its E-configuration have exhibited excellent in vitro antichagasic and antileishmanial profiles. Preliminary assays on both parasites suggested that the most active derivatives act through oxidative and nitrosative stress mechanisms; however, their exact mode of actions as anti-trypanosomal and anti-leishmanial agents have not been completely elucidated. This motivated to perform a molecular docking study on essential trypanosomatid enzymes such as superoxide dismutase (SOD), trypanothione reductase (TryR), cysteine-protease (CP) and pteridine reductase 1 (PTR1). In addition, to understand the experimental results of nitric oxide production obtained for infected macrophages with Leishmania parasite, a molecular docking was evaluated on nitric oxide synthase (iNOS) enzyme of Rattus norvegicus. Both diastereomers (E and Z) of the 4-phthalazinyl-hydrazones were docked on the mentioned targets. In general, molecular docking on T. cruzi enzymes revealed that the E-diastereomers exhibited lower binding energies than Z-diastereomers on the Fe-SOD and CP enzymes, while Z-diastereomers showed lower docking energies than E-isomers on TryR enzyme. For the Leishmania docking studies, the Z-isomers exhibited the best binding affinities on the PTR1 and iNOS enzymes, while the TryR enzyme showed a minor dependence with the stereoselectivity of the tested phthalazines. However, either the structural information of the ligand-enzyme complexes or the experimental data suggest that the significant antitrypanosomatid activity of the most active derivatives is not associated to the inhibition of the SOD, CP and PTR1 enzymes, while the TryR inhibition and nitric oxide generation in host cells emerge as interesting antitrypanosomatid therapeutic targets.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N370 – PubChem

Discovery of Phthalazine

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Artificial photosynthesis: Opportunities and challenges of molecular catalysts

Molecular catalysis plays an essential role in both natural and artificial photosynthesis (AP). However, the field of molecular catalysis for AP has gradually declined in recent years because of doubt about the long-term stability of molecular-catalyst-based devices. This review summarizes the development history of molecular-catalyst-based AP, including the fundamentals of AP, molecular catalysts for water oxidation, proton reduction and CO2 reduction, and molecular-catalyst-based AP devices, and it provides an analysis of the advantages, challenges, and stability of molecular catalysts. With this review, we aim to highlight the following points: (i) an investigation on molecular catalysis is one of the most promising ways to obtain atom-efficient catalysts with outstanding intrinsic activities; (ii) effective heterogenization of molecular catalysts is currently the primary challenge for the application of molecular catalysis in AP devices; (iii) development of molecular catalysts is a promising way to solve the problems of catalysis involved in practical solar fuel production. In molecular-catalysis-based AP, much has been attained, but more challenges remain with regard to long-term stability and heterogenization techniques.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N505 – PubChem

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Reactions of uracils. 21. Zwitterionic heteropolycyclic uracils by a novel three-component reaction: Iminophosphorane, isocyanate, heteroarene

The novel three-component reaction of (uracil-6-ylimino)phosphorane 1, isocyanate 2, and (substituted) pyridines gives, in a one-pot procedure, a variety of new pyrido[1′,2′:3,4]pyrimido[4,5-d]pyrimidines 3-11. The zwitterionic ground state of these new ring systems is i.a. established by means of solvatochromism, Hammett correlations, NMR, and X-ray analysis. Replacement of the pyridine by isoquinoline and phthalazine gives access to the novel ring systems pyrimido[4′,5′:4,5]pyrimido[6,1-a]isoquinoline and -phthalazine, which are formed as dihydro derivatives (14, 15) or as zwitterions (13, 17), depending on the reaction conditions. Oxidative cleavage of the phthalazine 15 in nitrobenzene affords the pyrimido[4,5-d]pyrimidines 16.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N466 – PubChem

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Ligand-Accelerated Iron Photocatalysis Enabling Decarboxylative Alkylation of Heteroarenes

A mild, practical protocol for the decarboxylative alkylation of heteroarenes has been accomplished via iron photocatalysis. A diverse range of carboxylic acids readily undergo oxidative decarboxylation and then couple with a broad array of heteroarenes in this transformation. The photoexcited state lifetimes of iron complexes are typically much shorter than those of iridium and ruthenium complexes. Here we describe our effort on iron photocatalysis by utilizing the intramolecular charge transfer pathway of iron-carboxylate complexes.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N259 – PubChem

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Six-Membered Ring Systems: Diazines and Benzo Derivatives

Found in natural products, and frequently used as flavoring agents or as building blocks for pharmaceuticals, diazines and their benzo derivatives possess a diverse set of properties, allowing abroad range of applications, spanning from medicinal chemistry to electrochemistry. New diazine-based natural products continue to be isolated and studied. In addition, new syntheses, reactions, andapplications of diazine-based compounds are reported every year. Recent advances in the development of new preparations, reactions, and applications of diazines and their benzo derivatives as well asthe discovery of new diazine-based natural products, published in the literature in 2017, are discussed in this review.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N365 – PubChem

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Thermal [3?+?2] cycloaddition of phthalazinium dicyanomethanide with allenoates

The thermal [3 + 2] cycloaddition reaction of phthalazinium dicyanomethanide with various allenoates worked efficiently under mild reaction conditions to give functionalized tetrahydropyrrolo[2,1-a]phthalazine derivatives in good to excellent yields and excellent diastereoselectivities.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N467 – PubChem

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Molecular dynamics simulation of organic crystals: Introducing the CLP-dyncry environment

The CLP-dyncry molecular dynamics (MD) program suite and force field environment is introduced and validated with its ad hoc features for the treatment of organic crystalline matter. The package, stemming from a preliminary implementation on organic liquids (Gavezzotti & Lo Presti, 2019), includes modules for the preliminary generation of molecular force field files from ab initio derived force constants, and for the preparation of crystalline simulation boxes from general crystallographic information, including Cambridge Structural Database CIFs. The intermolecular potential is the atom-atom Coulomb-London-Pauli force field, well tested as calibrated on sublimation enthalpies of organic crystals. These products are then submitted to a main MD module that drives the time integration and produces dynamic information in the form of coordinate and energy trajectories, which are in turn processed by several kinds of crystal-oriented analytic modules. The whole setup is tested on a variety of bulk crystals of rigid, non-rigid and hydrogen-bonded compounds for the reproduction of radial distribution functions and of crystal-specific collective orientational variables against X-ray data. In a series of parallel tests, some advantages of a dedicated program as opposed to software more oriented to biomolecular simulation (Gromacs) are highlighted. The different and improved view of crystal packing that results from joining static structural information from X-ray analysis with dynamic upgrades is also pointed out. The package is available for free distribution with I/O examples and Fortran source codes.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N161 – PubChem