Some scientific research about Phthalazine

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In vitro drug-drug interaction potential of sulfoxide and/or sulfone metabolites of albendazole, triclabendazole, aldicarb, methiocarb, montelukast and ziprasidone

Background: The use of polypharmacy in the present day clinical therapy has made the identification of clinical drug-drug interaction risk an important aspect of drug development process. Although many drugs can be metabolized to sulfoxide and/or sulfone metabolites, seldom is known on the CYP inhibition potential and/or the metabolic fate for such metabolites. Objective: The key objectives were: a) to evaluate the in vitro CYP inhibition potential of selected parent drugs with sulfoxide/sulfone metabolites; b) to assess the in vitro metabolic fate of the same panel of parent drugs and metabolites. Methods: In vitro drug-drug interaction potential of test compounds was investigated in two stages; 1) assessment of CYP450 inhibition potential of test compounds using human liver microsomes (HLM); and 2) assessment of test compounds as substrate of Phase I enzymes; including CYP450, FMO, AO and MAO using HLM, recombinant human CYP enzymes (rhCYP), Human Liver Cytosol (HLC) and Human Liver Mitochondrial (HLMit). All samples were analysed by LC-MS-MS method. Results: CYP1A2 was inhibited by methiocarb, triclabendazole, triclabendazole sulfoxide, and ziprasidone sulfone with IC50 of 0.71 muM, 1.07 muM, 4.19 muM, and 17.14 muM, respectively. CYP2C8 was inhibited by montelukast, montelukast sulfoxide, montelukast sulfone, tribendazole, triclabendazole sulfoxide, and triclabendazole sulfone with IC50 of 0.08 muM, 0.05 muM, 0.02 muM, 3.31 muM, 8.95 muM, and 1.05 muM, respectively. CYP2C9 was inhibited by triclabendazole, triclabendazole sulfoxide, triclabendazole sulfone, montelukast, montelukast sulfoxide and montelukast sulfone with IC50 of 1.17 muM, 1.95 muM, 0.69 muM, 1.34 muM, 3.61 muM and 2.15 muM, respectively. CYP2C19 was inhibited by triclabendazole and triclabendazole sulfoxide with IC50 of 0.25 and 0.22, respectively. CYP3A4 was inhibited by montelukast sulfoxide and triclabendazole with IC50 of 9.33 and 15.11, respectively. Amongst the studied sulfoxide/sulfone substrates, the propensity of involvement of CY2C9 and CYP3A4 enzyme was high (approximately 56% of total) in the metabolic fate experiments. Conclusion: Based on the findings, a proper risk assessment strategy needs to be factored (i.e., perpetrator and/or victim drug) to overcome any imminent risk of potential clinical drug-drug interaction when sulfoxide/sulfone metabolite(s) generating drugs are coadministered in therapy.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N166 – PubChem

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Reactions of phthalazine, quinazoline, 4,7-phenanthroline and 2,3?-bipyridine with ruthenium carbonyl

The reactions of [Ru3(CO)12] with four aromatic diazines have been studied in THF at reflux temperature. With phthalazine (L1), the compound [Ru3(mu-kappa2N 2N3-L1)(mu-CO)3(CO)7] (1), which contains an intact phthalazine ligand in an axial position bridging an Ru-Ru edge through both N atoms, is initially formed but it reacts with more phthalazine to give [Ru3(kappaN2-L1)(mu- kappa2N2N3-L1)(mu-CO) 3(CO)6] (2), in which a pi-pi stacking interaction between the aromatic rings of both ligands determines their position in cluster axial sites on the same face of the Ru3 triangle. With quinazoline (HL2), the cyclometalated hydrido decacarbonyl derivative [Ru 3(mu-H)(mu-kappa2N3C4-L 2)(CO)10] (3) is initially produced but it partially decarbonylates under the reaction conditions to give [Ru6(mu-H) 2(mu-kappa2N3C4-L 2)(mu3-kappa3-N1N 3C4-L2)(CO)19] (4), which results from the displacement of a CO ligand of 3 by the uncoordinated N1 atom of another molecule of 3. With 4,7-phenanthroline (H2L 3), the stepwise formation of the cyclometalated derivatives [Ru 3(mu-H)(mu-kappa2N4C3-HL 3)(CO)10] (5) and two isomers of [Ru6(mu-H) 2(mu4-kappa4N4C 3N7C8-L3)(CO)20] (6a, 6b) takes place. In compounds 6a and 6b, two Ru3(mu-H)(CO) 10 trinuclear units are symmetrically (C2 in 6a or C S in 6b) bridged by a doubly-cyclometalated 4,7-phenanthroline ligand. With 2,3?-bipyridine (HL4), two products have been isolated, [Ru3(mu-H)(mu-kappa2N 3?C4?-L4)(CO)10] (7) and [Ru3(mu-H)(mu-kappa3N2N 3?C2?-L4)(CO)9] (8). While compound 7 contains an N3?C4?- cyclometalated 2,3?-bipyridine, in compound 8 an N 3?C2?-cyclometalation is accompanied by the coordination of the N2 atom of the remaining pyridine fragment. The structures of compounds 2, 3, 4, 6a and 8 have been determined by X-ray diffraction crystallography.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N94 – PubChem

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Surface-enhanced Raman spectroscopy toward application in plasmonic photocatalysis on metal nanostructures

Among photothermal, photovoltaic and photochemical techniques, photochemistry is superior in energy storage and transportation by converting photons into chemical fuels. Recently plasmonic photocatalysis, based on localized surface plasmon resonance (LSPR) generated from noble metal nanostructures, has attracted much attention. It promotes photochemical reaction efficiency by optimizing the solar spectrum absorption and the surface reaction kinetics. The deeper understanding is in urgent need for the development of novel plasmonic photocatalysts. Surface-enhanced Raman spectroscopy (SERS), which is also originated from the LSPR effect, provides an excellent opportunity to probe and monitor plasmonic photoreactions in situ and in real-time, with a very high surface sensitivity and energy resolution. Here, fundamentals of plasmonic photocatalysis and SERS are first presented based on their connections to the LSPR effect. Following by a validity analysis, latest studies of SERS applied for the plasmon mediated photochemical reaction are reviewed, focusing on the reaction kinetics and mechanism exploration. Finally, limitations of the present study, as well as the future research directions, are briefly analyzed and discussed.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N105 – PubChem

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The impact of single nucleotide polymorphisms on human aldehyde oxidase

Aldehyde oxidase (AO) is a complex molybdo-flavoprotein that belongs to the xanthine oxidase family. AO is active as a homodimer, and each 150-kDa monomer binds two distinct [2Fe2S] clusters, FAD, and the molybdenum cofactor. AO has an important role in the metabolism of drugs based on its broad substrate specificity oxidizing aromatic aza-heterocycles, for example, N1- methylnicotinamide and N-methylphthalazinium, or aldehydes, such as benzaldehyde, retinal, and vanillin. Sequencing the 35 coding exons of the human AOX1 gene in a sample of 180 Italian individuals led to the identification of relatively frequent, synonymous, missense and nonsense single-nucleotide polymorphisms (SNPs). Human aldehyde oxidase (hAOX1) was purified after heterologous expression in Escherichia coli. The recombinant protein was obtained with a purity of 95% and a yield of 50 mug/l E. coli culture. Site-directed mutagenesis of the hAOX1 cDNA allowed the purification of protein variants bearing the amino acid changes R802C, R921H, N1135S, and H1297R, which correspond to some of the identified SNPs. The hAOX1 variants were purified and compared with the wild-type protein relative to activity, oligomerization state, and metal content. Our data show that the mutation of each amino acid residue has a variable impact on the ability of hAOX1 to metabolize selected substrates. Thus, the human population is characterized by the presence of functionally inactive hAOX1 allelic variants as well as variants encoding enzymes with different catalytic activities. Our results indicate that the presence of these allelic variants should be considered for the design of future drugs. Copyright

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Phthalazine – Wikipedia,
Phthalazine | C8H6N180 – PubChem

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Functional chemical groups that may likely become a source for the synthesis of novel central nervous system (CNS) acting drugs

Introduction: Central Nervous System (CNS) disorders are on increase perhaps due to genetic, enviromental, social and dietetic factors. Unfortunately, a large number of CNS drugs have adverse effects such as addiction, tolerance, psychological and physical dependence. In view of this, literature search was carried out with a view to identify functional chemical groups that may serve as lead molecules for synthesis of compounds that may have CNS activity. Methods: The search revealed that heterocycles that have heteroatoms such as nitrogen (N), sulphur (S) and oxygen (O) form the largest class of organic compounds. They replace carbon in a benzene ring to form pyridine. Compounds with furan, thiophene, pyrrole, pyridine, azole, imidazole, indole, purine, pyrimidine, esters, carboxylic acid, aldehyde, pyrylium, pyrone, pyrodine, barbituric acid, barbiturate, quinoline, quinolone, isoquinolone, coumarin, alkylpyridine, picoline, piperidine, diazine, carboxamide, flavonoid glycoside, oxindole, aminophenol, benzimidazole, benzoxazole, benzothiazole, and chromone chemical groups among others may have CNS effects ranging from depression passing through euphoria to convulsion. Results and Conclusion: Examples of the compounds with the functional groups include but not limited to coal tar, pyridostigmine, pralidoxime, quinine, mefloquine, pyrilamine, pyronaridine, ciprofloxacin and piroxicam. A number of them can undergo keto-enol tautomerism. Chiral amines may be used for derivation of chiral carboxylic acids which are components of tautomers. Some tautomers may cause parkinsonism and Stevens Johnson syndrome.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N381 – PubChem

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The reaction of fullerene C60 with phthalazine: The mechanochemical solid-state reaction yielding a new C60 dimer versus the liquid-phase reaction affording an open-cage fullerene

The reaction of fullerene C60 with phthalazine was studied both in solution and in the solid state using the high-speed vibration-milling technique. The reaction in solution gave open-cage fullerene derivative 1 in 44% yield by a one-pot reaction. In contrast, the solid-state reaction afforded dimeric derivative 2 as the sole product. Dimeric derivative 2 was found to undergo intramolecular [2 + 2] cycloaddtion between the two C60 cages located in close proximity to give a new C60 dimer 6 in quantitative yield. The structures of these new derivatives of C60 were determined by spectroscopic methods, and the electrochemical behavior of 2 and 6 was also studied.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N308 – PubChem

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Spectroscopic characterization and quantum chemical investigation of molecular structure and vibrational spectra of phthalazine-1(2H)-one

In this study, vibrational and electronic transition analysis of phthalazine-1(2H)-one have been presented using experimental techniques FT-IR, FT-Raman and density functional theory (DFT) calculation. The structural properties of the molecule in the ground state have been calculated using DFT employing B3LYP/6-311++G(d,p) basis set. Optimized geometrical parameters have been interpreted and compared with the experimental values. The complete assignments have been performed on the basis of the experimental data and potential energy distribution (PED) of the vibrational modes. The calculated HOMO and LUMO energies and energy difference (DeltaEHOMO?LUMO = ? 4.876 eV), confirm that charge transfers occur within the molecule. The stability of the molecule arising from hyperconjugative interactions and the charge delocalization has been analyzed using natural bond orbital?s analysis (NBO). The specific heat, Gibb?s free energy, and entropy of molecule have been calculated as a function of temperature by using statistical mechanics coupled with quantum chemical calculation. Observed vibrational wave numbers have been compared with calculated values, and found to be in agreement with experimental results. The study of dielectric properties like dielectric constant at microwave frequency, static dielectric constant and dielectric constant at optical frequency of Phthalazine-1(2H)-one have been determined. The dielectric relaxation studies provide information about the molecular structure and intermolecular interaction between phthalazine-1(2H)-one and alcohol mixture.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N315 – PubChem

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Preparation of onium salts of a reduced anthracenone crown ether macrocycle: A reactivity series involving pyridine, phosphine, thiophene, nitrile and primary amide nucleophiles

Reaction of mineral acids with a cyclic macromolecule containing a secondary alcohol produces ammonium, phosphonium, thiophene, and amide adducts via a carbocation intermediate. X-ray crystallography confirms the structures of the products, including those when two competing nucleophiles are present. A reactivity series that mirrors the nucleophilicity index, where reactivity decreases in the order thiophene >pyridine >primary amides >alkyl nitriles >> aromatic nitriles (unreactive), results. Addition of metal ions to ammonium adducts dissolved in acetonitrile produces secondary amides via the Ritter amide synthesis. Copyright

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Phthalazine – Wikipedia,
Phthalazine | C8H6N279 – PubChem

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Organometallic Complexes of Azines

Organometallic complexes of practically unsubstituted (non-chelating) azines and their benzannulated derivatives, possible N-heterocyclic carbenes containing at least one double bond, and boron-, boron?nitrogen, silicon-, tri- and hexaphosphorus analogs of azines are considered in the view of their synthetic availability, coordination modes, and possible application in catalysis and materials chemistry.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N379 – PubChem

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Nature of Reissert Analogs Derived from N,N-Dialkyl and N,N-Diaryl Carbamoyl Chlorides

Reissert analogs were prepared from the reaction of isoquinoline and phthalazine with carbamoyl chlorides and cyanide using the methylene chloride-water method.Alkylation, condensation, Michael addition, and hydrolysis reactions of these Reissert analogs have been studied and found in many cases, to be similar to those of the isoquinoline Reissert compound.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N220 – PubChem