Final Thoughts on Chemistry for 4-(4-Fluoro-3-(piperazine-1-carbonyl)benzyl)phthalazin-1(2H)-one

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Induction of apoptosis in MDA-MB-231 breast cancer cells by a PARP1-targeting PROTAC small molecule

Poly (ADP-ribose) polymerase-1 (PARP1) is a major member of the PARP superfamily that is involved in DNA damage signalling and other important cellular processes. Here we report the development of a small molecule targeting PARP1 based on the PROTAC strategy. In the MDA-MB-231 cell line, the representative compound 3 can induce significant PARP1 cleavage and programmed cell death.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N834 – PubChem

Simple exploration of Phthalazine

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The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity

Protein lysine methyltransferases (PKMTs) regulate diverse physiological processes including transcription and the maintenance of genomic integrity. Genetic studies suggest that the PKMTs SUV420H1 and SUV420H2 facilitate proficient nonhomologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation (me2 and me3, respectively) of lysine 20 on histone 4 (H4K20). Here we report the identification of A-196, a potent and selective inhibitor of SUV420H1 and SUV420H2. Biochemical and co-crystallization analyses demonstrate that A-196 is a substrate-competitive inhibitor of both SUV4-20 enzymes. In cells, A-196 induced a global decrease in H4K20me2 and H4K20me3 and a concomitant increase in H4K20me1. A-196 inhibited 53BP1 foci formation upon ionizing radiation and reduced NHEJ-mediated DNA-break repair but did not affect homology-directed repair. These results demonstrate the role of SUV4-20 enzymatic activity in H4K20 methylation and DNA repair. A-196 represents a first-in-class chemical probe of SUV4-20 to investigate the role of histone methyltransferases in genomic integrity.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N84 – PubChem

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Response Theory and Calculations of Spin-Orbit Coupling Phenomena in Molecules

We review response theory and calculations of molecular properties involving spin-orbit interactions. The spin-orbit coupling is evaluated for reference states described by single- or multi-configuration self-consistent field wave functions. The calculations of spin-orbit related properties rest on the formalism of linear and quadratic response functions for singlet and triplet perturbations when no permutational symmetry in the two-electron operators is assumed and from which various triplet as well as singlet response properties are derived. The spin-orbit coupling matrix elements between singlet and triplet states are evaluated as residues of (multi-configuration) linear response functions, and are therefore automatically determined between orthogonal and non-interacting states. Spin-forbidden radiative transition intensities and lifetimes are determined from the spin-orbit coupling induced dipole transitions between two electronic states of different multiplicity and are obtained as residues of quadratic response functions. The potential of the theory and its range of applications is illustrated by a selection of recent investigations covering different molecular phenomena. The applications include second-order energy contributions, intensity rearrangement in electron spectra, calculation of predissociative lifetimes of dicationic states, assignment of triplet bands in absorption spectra, intersystem crossings and reactivity, external heavy atom effects on S-T transitions, phosphorescence spectra and radiative lifetimes of triplet states. We give an outlook on spin-orbit interaction induced phenomena in extended systems and on applications to general spin catalysis phenomena.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N22 – PubChem

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Experimental study on the thermochemistry of 1-(2H)-phthalazinone and phthalhydrazide

The standard (p{ring operator} = 0.1 MPa) molar enthalpies of combustion of 1-(2H)-phthalazinone and phthalhydrazide, both in the solid phase, were measured at T = 298.15 K by static bomb calorimetry. Further, the standard molar enthalpies of sublimation, at T = 298.15 K, of these two phthalazine derivatives were derived from the Knudsen effusion technique. The combustion calorimetry results together with those obtained from the Knudsen effusion technique, were used to derive the standard molar enthalpies of formation, at T = 298.15 K, in the gaseous phase for 1-(2H)-phthalazinone and phthalhydrazide, respectively as, (79.1 ¡À 1.8) kJ ¡¤ mol-1 and -(107.4 ¡À 2.4) kJ ¡¤ mol-1.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N363 – PubChem

Brief introduction of 2-(3-(4-Bromo-2-fluorobenzyl)-4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid

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Virtual screening: An effective tool for lead structure discovery?

Different methods of virtual screening as a tool for lead structure discovery are described. They range from structure based docking procedures to ligand based methods such as the chemical features based pharmacophore hypothesis approach. A review on several successful applications of virtual screening is given. Different approaches have been described to derive pharmacophore models, which were subsequently used for 3D database searching. The studies so far published cover a wide range of pharmacological applications. The results hereby obtained clearly indicate that focused assessment of corporate databases by virtual screening using well validated pharmacophore models yield to a significant improvement in lead structure determination compared to high throughput screening.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N879 – PubChem

Awesome and Easy Science Experiments about 6-Amino-2,3-dihydrophthalazine-1,4-dione

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Immunoassays for therapeutic drug monitoring and clinical toxicology

Immunoassays are quantitative analytical methods that make use of antibodies as reagents. The highly specific binding and large association constants (Ka) of antibodies make them useful for detection and quantitation of analytes in complex sample matrices such as body fluids including blood, urine, saliva, sweat, or vitreous humor. Methods based on immunochemical reactions are some of the most sensitive and specific assays available to laboratorians. Many formats of immunoassays have been automated and are widely used in the clinical laboratory for therapeutic drug monitoring (TDM).

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Phthalazine – Wikipedia,
Phthalazine | C8H6N541 – PubChem

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The H-1 NMR Solvent Shifts and Reactivity Parameters of Several Aromatic Compounds

H-1 NMR solvent shifts were measured for 7 aromatic hydrocarbons and 13 heteroaromatic compounds.The chemical shifts can be correlated to the selfpolarizabilities of the carbon atoms attached to the hydrogens in the aromatic hydrocarbons and will be of use in presicting the reactivities of the compounds.However, in the case of heteroaromatic compounds, no good correlation has been found between the reactivity parameters and the H-1 NMR solvent shifts.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N433 – PubChem

The Absolute Best Science Experiment for 2-Fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid

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PHTHALAZINONE KETONE DERIVATIVE, PREPARATION METHOD THEREOF, AND PHARMACEUTICAL USE THEREOF

A phthalazinone ketone derivative as represented by formula (I), a preparation method thereof, a pharmaceutical composition containing the derivative, a use thereof as a poly (ADP-ribose) polymerase (PARP) inhibitor, and a cancer treatment method thereof.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N767 – PubChem

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

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Reactive Oxygen Species Localization Programs Inflammation to Clear Microbes of Different Size

How the number of immune cells recruited to sites of infection is determined and adjusted to differences in the cellular stoichiometry between host and pathogen is unknown. Here, we have uncovered a role for reactive oxygen species (ROS) as sensors of microbe size. By sensing the differential localization of ROS generated in response to microbes of different size, neutrophils tuned their interleukin (IL)-1beta expression via the selective oxidation of NF-kappaB, in order to implement distinct inflammatory programs. Small microbes triggered ROS intracellularly, suppressing IL-1beta expression to limit neutrophil recruitment as each phagocyte eliminated numerous pathogens. In contrast, large microbes triggered ROS extracellularly, amplifying IL-1beta expression to recruit numerous neutrophils forming cooperative clusters. Defects in ROS-mediated microbe size sensing resulted in large neutrophil infiltrates and clusters in response to small microbes that contribute to inflammatory disease. These findings highlight the impact of ROS localization on signal transduction.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N653 – PubChem

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Meldrum?s acid in organic synthesis, an outlook to reaction media

Meldrum?s acid, a white solid which was prepared for the first time by Andrew Norman in 1908, is a versatile and efficient motif in chemistry. The rigid structure, low steric hindrance, in addition with high acidity of the C5-H, are some unique chemical properties of this O-containing heterocycle. Several organic compounds based on Meldrum?s acid have interesting applications in biology, industry and drugs. Its special structure makes it a good target for both nucleophilic as well as electrophilic attack. Preparation of different forms of these scaffolds, with a glance on the reaction media, has been reviewed. In addition, other part of the manuscript is based on heat and solvent of the reaction media. These factors focused on green chemistry rules. This review classified the multi-component transformations of Meldrum?s acid as one of their substrates with respect to these two important aspects of green synthesis up to middle of 2016.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N319 – PubChem