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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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Inter-a inhibitor proteins maintain neutrophils in a resting state by regulating shape and reducing ROS production

The plasma levels of inter-a inhibitor proteins (IAIPs) are decreased in patients with sepsis and the reduced levels correlate with increased mortality. In the present study, we examined the effects of IAIPs on human neutrophils to better understand the beneficial effects of IAIPs in the treatment of sepsis. We demonstrated that IAIPs induced a spherical shape that was smaller in size with a smooth cellular surface in a concentration-dependent manner. These changes were inhibited by a specific antibody against IAIPs. In contrast, bikunin, light chain of IAIP, had no effect on neutrophil morphology. The neutrophils treated with IAIPs could easily pass through the artificial microcapillaries and were prevented from entrapment inside the capillaries. Coincubation of human blood neutrophils with a confluent human vascular endothelial monolayer showed that adhesion of neutrophils on endothelial cells was suppressed by treatment with IAIPs. IAIPs inhibited the spontaneous release of reactive oxygen species (ROS) in a concentration-dependent fashion. ROS inhibition was associated with reductions in p47phoxphosphorylation on Ser328. These results suggest that IAIP-induced morphological changes that render neutrophils quiescent, facilitate passage through the microvasculature, and reduce adhesion to vascular endothelial cells and production of ROS. Thus, IAIP plays a key role in controlling neutrophil activation.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N572 – 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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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N220 – PubChem

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Reactions of Phthalazinium-2-(unsubstituted methanide) and -2-dicyanomethanide 1,3-Dipoles with Alkene and Alkyne Dipolarophiles: Stereochemistry and Secondary Reactions: Substituted Pyrrolo[2,1-a]phthalazines

Phthalazinium-2-methanide 1,3-dipoles display stereospecific cycloadditions with alkene dipolarophiles; the products may vary from pure endo to pure exo adducts or mixtures of both, and the cycloadducts from both alkenes and alkynes may undergo further in situ oxidations, dehydrocyanations or H-tautomerisations.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N92 – PubChem

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Role of ligands in catalytic water oxidation by mononuclear ruthenium complexes

Since first reported in 2005, mononuclear ruthenium water oxidation catalysts have attracted a great deal of attention due to their catalytic performance and synthetic flexibility. In particular, ligands coordinated to a Ru metal centre play an important role in the catalytic mechanisms, exhibiting significant impact on catalyst efficiency, stability and activity towards water oxidation. This review focuses on finding possible correlations between the ligand effects and activity of mononuclear Ru aqua and non-aqua complexes as water oxidation catalysts. The ligand effects highlighted in the text include the electronic nature of core ligands and their substituents, the trans-cis effect, steric hindrance and the strain effect, the net charge effect, the geometric arrangement of the aqua ligand and the supramolecular effects, e.g., hydrogen bonding and influence of a pendant base. The outcome is not always obvious at the present knowledge level. Deeper understanding of the ligand effects, based on new input data, is mandatory for further progress towards a rational development of novel catalysts featuring enhanced activity in water oxidation.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N502 – PubChem

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GFP assay as a sensitive eukaryotic screening model to detect toxic and genotoxic activity of azaarenes

Azaarenes are nitrogen-containing polyaromatic heterocyclic compounds (NPAHs). The majority of the azaarenes found in the environment originate from anthropogenic sources. Concentrations of NPAHs found in the environment are reported to be one to two orders of magnitude lower than polycyclic aromatic hydrocarbons (PAHs) concentrations, yet their biological effects can be of similar magnitude. Very few studies on the genotoxicity of azaarenes are available in the literature. In the present study, a preliminary profile of both the toxic and genotoxic potential of 5 PAHs and their 20 aza-analogues were investigated. To assess the toxic and genotoxic activity, a green fluorescent protein (GFP) assay based on the yeast Saccharomyces cerevisiae was selected. To compare the sensitivity of this eukaryotic short-term assay with bacterial screening tests, the Toxi-Chromotest for toxicity and SOS-Chromotest for genotoxicity assessment were also performed. This comparison indicates that in most cases, the yeast GFP assay is apparently of comparable specificity to the bacterial toxicity or genotoxicity tests with respect to the correlation of positive/negative responses, but much more sensitive with respect to the effective concentration values. In the cases of phenazine, phenanthridine, 1,10-phenanthroline, or 4,7-phenanthroline, one to two orders of magnitude lower IC20 and minimum genotoxic concentration values in the yeast GFP assay were observed. In this study, the authors present evidence that genotoxicity assessment using the yeast GFP assay can provide a simple system to monitor the activity of these environmental pollutants that could possess mutagenic potential at low concentrations.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N57 – PubChem