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Cardiac stimulant 1-(3- or 4-substituted piperidino)phthalazines

1-(3- or 4-substituted piperidino)phthalazines of the formula wherein R is C1-6 alkyl; Y is a 3- or 4-position substituent and is -X-(CHR1)m-Z wherein R1 is hydrogen or C1-6 alkyl; m is 1 or 2; X is oxygen or a direct link provided that when m is 1, X is a direct link; and Z is -N(R2)COR3, -N(R2)COOR3, -N(R2)SO2R3, -N(R2)SO2NR4R5, -N(R2)SOR3, -N(R2)CONR4R5 or -OCONR4R5, wherein R2 and R5 are each independently hydrogen or C1-6 alkyl; R3 is C1-6 alkyl, phenethyl, benzyl, C3-7 cycloalkyl, phenyl or pyridyl; R4 is hydrogen or R3; provided that when X is a direct link, R3 or R4 is C3-7 cycloalkyl; the pharmaceutically acceptable acid addition salts thereof; processes for their preparation; and their use as cardiac stimulants and phosphodiesterase inhibitors

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Phthalazine – Wikipedia,
Phthalazine | C8H6N692 – PubChem

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One of the major reasons for studying chemical kinetics is to use measurements of the macroscopic properties of a system, category: phthalazine, such as the rate of change in the concentration of reactants or products with time.In a article, mentioned the application of 253-52-1, Name is Phthalazine, molecular formula is C8H6N2

Aldehyde oxidase 1 (AOX1) in human liver cytosols: Quantitative characterization of AOX1 expression level and activity relationships

Aldehyde oxidase 1 (AOX1) is a cytosolic enzyme highly expressed in liver and plays a key role in metabolizing drugs containing aromatic azaheterocyclic substituents. Rapid metabolism catalyzed by AOX1 can cause a drug to exhibit high clearance, low exposure, and hence decreased efficacy or even increased toxicity (if AOX1 generated metabolites are toxic). There is a need to develop the correlation between AOX1 expression levels and AOX1-substrate clearance. A fast, sensitive, and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quantify AOX1 in human liver cytosol for the first time. This LC-MS/MS method includes a straightforward ultrafiltration fractionation step and gives great selectivity and wide dynamic range (5.2 pM to 20.7 nM). The AOX1 levels in human liver cytosols of 20 donors were quantified using this method to investigate individual differences in AOX1 expression. No significant individual or gender differences in AOX1 levels were observed, although male donors exhibited a broader distribution than female donors (0.74-2.30 pmol/mg versus 0.74-1.69 pmol/mg, respectively). The AOX1 protein levels measured by LC-MS/MS were consistent with those measured by an enzyme-linked immunosorbent assay. Several donors have a normal AOX1 protein level but low enzyme activity, which might be due to cofactor deficiency, single nucleotide polymorphism, or homodimer dissociation. Cytosols from donors with chronic alcohol consumption had low AOX1-catalyzed carbazeran oxidation activities (<51 mul/min per milligram compared with a median of 455 mul/min per milligram), but preserved similar AOX1 protein expression levels (approximately 15% less than the median value). Copyright Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. category: phthalazine, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 253-52-1, in my other articles.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N156 – PubChem

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Effects of ponalrestat, an aldose reductase inhibitor, on neutrophil killing of Escherichia coli and autonomic function in patients with diabetes mellitus

In diabetic subjects, polyol pathway activity might inhibit neutrophil function and cause nerve damage. The effects of ponalrestat, an aldose reductase inhibitor, were assessed on neutrophil intracellular killing of Escherichia coli and on autonomic function in diabetic subjects in a randomized double-blind, placebo-controlled, crossover trial. We studied 31 diabetic subjects with autonomic dysfunction and 21 age- and sex-matched control subjects. During two 12-wk treatment periods, the diabetic subjects took either 600 mg of ponalrestat or matching placebo once daily. Neutrophil killing of E. coli was measured by a microbiological assay technique. K(max) by neutrophils from the diabetic subjects was lower than in the control group (K(max) of diabetic subjects 54.5 ¡À 26.4 vs. control subjects 67.3 ¡À 16.3, P = 0.045). Ponalrestat significantly increased bacterial killing in the diabetic subjects (K(max) of ponalrestat 75.1 ¡À 16.5 vs. placebo 58.2 ¡À 20.8, P = 0.003) so that there was no longer any significant difference in K(max) between the control subjects and the diabetic subjects on active treatment. Ponalrestat had no significant effect on a range of standard cardiovascular autonomic nerve function tests. We conclude that neutrophil killing of E. coli is impaired in diabetic subjects with autonomic dysfunction. This is restored to normal by ponalrestat.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N850 – PubChem

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Fluorescent sensors for the detection of hydrazine in environmental and biological systems: Recent advances and future prospects

Being a widely used raw material in the manufacture of synthetic catalysts, agricultural chemicals and pharmaceutical products, hydrazine (N2H4) caused irreversible pollution to air, water and soil in our environment owing to its high toxic impact and massive use. In addition, during the metabolism process of certain drugs, such as isoniazid (INH), hydrazine can also be released, causing serious harm to human body. It has been proved by previous researches that hydrazine could cause several adverse effects, including the inhibition of molecular metabolism, mitochondrial oxidation and DNA damage. Thus, methods which could sensitively and selectively detect hydrazine in vivo and in vitro are in urgent need. Fluorescent sensors, a powerful tool for efficiently evaluating the hydrazine levels in environmental and living systems with minimal perturbation, were widely studied over the past few years. Since the number of the fluorescent sensors for hydrazine detection has grown rapidly, this review attempted to present a well-organized overview of existing design strategies for developing fluorescent sensors for hydrazine, including both reaction-based sensors and material-based sensors from 2011 to the present. The molecular structures, sensing mechanisms and applications of these sensors were emphatically classified and discussed. Moreover, the following prospects and challenges of this field were also provided.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N510 – PubChem

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An immunoassay for plasma cortisol based on chemiluminescence

An immunoassay procedure for the determination of cortisol in human plasma is described, which utilizes chemiluminescence as the end point. A cortisol-isoluminol conjugate serves as the chemiluminescent marker. The light emission by this conjugate upon oxidation is delayed by prior incubation with anti-cortisol IgG, but not by unrelated gamma-globulin. This delayed light emission was inhibited by cortisol in a dose-dependent manner, with a linear range of 20?1000 pg steroid/assay tube. A competitive protein binding assay based on this procedure was applied to methylene chloride extracts of cortisol from normal and pathological human plasma (2?40 mug/100 ml). Cortisol values obtained by this procedure agreed well with those obtained by radioimmunoassay, using the same antiserum with tritiated cortisol as the label (r = 0.98). The chemiluminescence immunoassay is comparable to radioimmunoassay with regard to sensitivity, specificity, precision and accuracy. The advantage of the new assay procedure is that it obviates the need for counting radioactivity and for separation of bound and free ligand.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N587 – PubChem

Discovery of 253-52-1

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Reference of 253-52-1, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.253-52-1, Name is Phthalazine, molecular formula is C8H6N2. In a article£¬once mentioned of 253-52-1

Synthesis of 3,4-benzo-7-hydroxy-2,9-diazabicyclo[3.3.1]non-7-enes by cyclization of 1,3-bis(silyl enol ethers) with quinazolines

A variety of functionalized 3,4-benzo-7-hydroxy-2,9-diazabicyclo[3.3.1]non- 7-enes were prepared by one-pot cyclizations of 1,3-bis(silyl enol ethers) with quinazolines. The mechanism of the cyclization was studied by B3LYP/6-31G(d) density functional theory computations. The products could be functionalized by Suzuki cross-coupling reactions. The reaction of 1,3-bis(silyl enol ethers) with phthalazine afforded open-chain rather than cyclization products. The Royal Society of Chemistry.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N222 – PubChem

Final Thoughts on Chemistry for 4-(4-Chlorobenzyl)phthalazin-1(2H)-one

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Synthetic Route of 53242-88-9, A catalyst don’t appear in the overall stoichiometry of the reaction it catalyzes, but it must appear in at least one of the elementary reactions in the mechanism for the catalyzed reaction. 53242-88-9, Name is 4-(4-Chlorobenzyl)phthalazin-1(2H)-one, molecular formula is C15H11ClN2O. In a Article£¬once mentioned of 53242-88-9

Synthesis of 2-Fluoroalkyl 4-Substituted Azepanes

Synthesis of di- and tri-substituted fluoroalkylated azepanes was achieved by ring expansion of pyrrolidines via a regioselective attack of nucleophiles on a bicyclic azetidinium intermediate. A broad scope of azepanes, substituted at C4 and bearing a alpha-trifluoromethyl, alpha-difluoromethyl or alpha-perfluorobutyl group, can be synthesized by this method by using a wide variety of nucleophiles.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N728 – PubChem

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Chemistry is traditionally divided into organic and inorganic chemistry. Computed Properties of C17H12BrFN2O3, The former is the study of compounds containing at least one carbon-hydrogen bonds.In a patent£¬Which mentioned a new discovery about 72702-95-5

Polyol pathway and diabetic peripheral neuropathy

This chapter critically examines the concept of the polyol pathway and how it relates to the pathogenesis of diabetic peripheral neuropathy. The two enzymes of the polyol pathway, aldose reductase and sorbitol dehydrogenase, are reviewed. The structure, biochemistry, physiological role, tissue distribution, and localization in peripheral nerve of each enzyme are summarized, along with current information about the location and structure of their genes, their alleles, and the possible links of each enzymes and its alleles to diabetic neuropathy. Inhibitors of pathway enzymes and results obtained to date with pathway inhibitors in experimental models and human neuropathy trials are updated and discussed. Experimental and clinical data are analyzed in the context of a newly developed metabolic model of the in vivo relationship between nerve sorbitol concentration and metabolic flux through aldose reductase. Overall, the data will be interpreted as supporting the hypothesis that metabolic flux through the polyol pathway, rather than nerve concentration of sorbitol, is the predominant polyol pathway-linked pathogenic factor in diabetic peripheral nerve. Finally, key questions and future directions for basic and clinical research in this area are considered. It is concluded that robust inhibition of metabolic flux through the polyol pathway in peripheral nerve will likely result in substantial clinical benefit in treating and preventing the currently intractable condition of diabetic peripheral neuropathy. To accomplish this, it is imperative to develop and test a new generation of “super-potent” polyol pathway inhibitors.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N896 – PubChem

Final Thoughts on Chemistry for Phthalazine

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Electric Literature of 253-52-1, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 253-52-1, molcular formula is C8H6N2, introducing its new discovery.

Olefin poly/oligomerizations by metal precatalysts bearing non?heterocyclic N?donor ligands

The use of transition metal complexes of non?heterocyclic N?donor ligands as olefin oligo/polymerization precatalysts is reviewed. These metal complexes with definite steric and electronic variations offer high catalytic activity resulting in the desired microstructure of the polymer products currently attracting significant attention by the catalysis community. This review primarily discusses the fundamental principles in the design of mononuclear, homodinuclear, heterodinuclear, homomultinuclear and heteromultinuclear transition metal complexes having non?heterocyclic N?donor ligands and their reactivity towards olefins in oligo/polymerization reactions. Numerous non?heterocyclic N?donor ligands of the donor types N2, NO, NP, NC, N2P, N2O, N2C, N2S, N3, NCP, NCp, NOCp, N3Cp, N2O2for mononuclear, N4, N2O2, N4O4, N3C, NCp2, N2Cp2, N2Indene2and N2S2Indene (Cp: cyclopentadiene) for bimetallic and N8, N8O4, N8O8and N12O4for multinuclear complex formations have been efficiently employed, and the resulting complexes display promising reactivity patterns with a variety of olefins. The majority of these catalytic systems are tethered with appropriate alkyl/aryl/alkyl?aryl substituents to afford the required steric hindrance to the metal center(s), and with functional groups for electronic variations. Such systems produce a linear polymer product in most of the cases, any deviation from this behavior resulting in the formation of oligomers. The major focus of this review is on reports published over the last 25 years in the research and development of non?heterocyclic, N?donor coordinated transition metal complexes with a variety of spacers. This review article is organized into main sections on the basis of the nuclearity of the transition metal complex; each subsection deals with complexes starting from late transition metals on the basis of ligand type.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N86 – PubChem

Archives for Chemistry Experiments of 6-Amino-2,3-dihydrophthalazine-1,4-dione

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Small-molecule luminescent probes for the detection of cellular oxidizing and nitrating species

Reactive oxygen species (ROS) have been implicated in both pathogenic cellular damage events and physiological cellular redox signaling and regulation. To unravel the biological role of ROS, it is very important to be able to detect and identify the species involved. In this review, we introduce the reader to the methods of detection of ROS using luminescent (fluorescent, chemiluminescent, and bioluminescent) probes and discuss typical limitations of those probes. We review the most widely used probes, state-of-the-art assays, and the new, promising approaches for rigorous detection and identification of superoxide radical anion, hydrogen peroxide, and peroxynitrite. The combination of real-time monitoring of the dynamics of ROS in cells and the identification of the specific products formed from the probes will reveal the role of specific types of ROS in cellular function and dysfunction. Understanding the molecular mechanisms involving ROS may help with the development of new therapeutics for several diseases involving dysregulated cellular redox status.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N666 – PubChem