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PHTHALAZINE DERIVATIVES FROM AROMATIC ALDAZINES

A Lewis acid mediated synthesis of phthalazine derivatives II and III from aromatic aldazines I is reported.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N367 – PubChem

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Sonogashira Reaction: Synthesis of Novel Derivatives of 3-Aryl-Substituted 6-Chloroimidazo[2, 1-a]phthalazines Catalyzed by Pd-Cu in Water

The reaction of 1-chloro-4-propargylaminophthalazine with various aryl halides catalyzed by Pd?Cu in the presence of potassium carbonate, as the base, in water leads to the one-pot formation of new derivatives of 3-aryl-substituted-6-chloroimidazo-[2, 1-a]phthalazines in moderate-to-good yields. Their structures are confirmed by IR and NMR spectra as well as elemental analyses. All the compounds prepared are screened in vitro for their anti-bacterial activities. The preliminary results indicate that some target compounds exhibit promising anti-bacterial potency.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N51 – PubChem

New explortion of Phthalazine

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Reaction of six-membered azaaromatics with allyltributyltin

Pyridazines were reacted with allyltributyltin in the presence of chloroformate to give 1-alkoxycarbonyl-6-allyl and 1-alkoxycarbonyl-4-allyldihydropyridazines as major and minor products, respectively. The reaction system was applied to other diazines and pyrimidine and pyrazine were shown to afford diallyltetrahydroadducts. Benzodiazines also gave allylation products in good yields. The reaction seems to be applicable to most six-membered azaaromatics.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N206 – PubChem

Properties and Exciting Facts About Phthalazine

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Evaluation of new dihydrophthalazine-appended 2,4-diaminopyrimidines against Bacillus anthracis: Improved syntheses using a new pincer complex

The synthesis and evaluation of ten new dihydrophthalazine-appended 2,4-diaminopyrimidines as potential drugs to treat Bacillus anthracis is reported. An improved synthesis utilizing a new pincer catalyst, dichlorobis[1-(dicyclohexylphosphanyl)-piperidine]palladium(II), allows the final Heck coupling to be performed at 90C using triethylamine as the base. These milder conditions have been used to achieve improved yields for new and previously reported substrates with functional groups that degrade or react at the normal 140C reaction temperature. An analytical protocol for separating the S and R enantiomers of two of the most active compounds is also disclosed. Finally, the X-ray structure for the most active enantiomer of the lead compound, (S)-RAB1, is given.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N304 – PubChem

Properties and Exciting Facts About Phthalazine

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FACILE RADICAL DECARBOXYLATIVE ALKYLATION OF HETEROAROMATIC BASES USING CARBOXYLIC ACIDS AND TRIVALENT IODINE COMPOUNDS

Many kinds of heteroaromatic bases were easily alkylated by the reaction of carboxylic acids with benzene or pentafluorobenzene via radical decarboxylative pathways.This system was further applied to the reaction with tetrahydrofurylcarboxylic acid, 1-(2,3,5-tri-O-benzyl)-D-ribofuranosylacetic acid, and 1-(2,3,5-tri-O-benzyl)-D-ribofuranosylcarboxylic acid for the model synthesis of C-nucleosides.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N449 – PubChem

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Novel triazolophthalazine-hydrazone hybrids as potential PCAF inhibitors: Design, synthesis, in vitro anticancer evaluation, apoptosis, and molecular docking studies

Three novel series of triazolophthalazine derivatives bearing hydrazone moiety were designed, synthesized, and evaluated for their anticancer activity against four human cancer cell lines by MTT assay. Six derivatives demonstrated comparable activity with Doxorubicin reference drug against the selected cancer cells. Especially, compound 16 showed the most potent activity with IC50 values of 5.70, 8.04, 11.15, and 4.25, muM against HePG2, MCF-7, PC3, and HCT-116 respectively. Also, compound 26 exhibited comparable inhibitory effect with that of Doxorubicin against the selected cancer cell lines with IC50 values of 6.45, 8.63, 12.28, and 7.03 muM against HePG2, MCF-7, PC3, and HCT-116 respectively. Investigation of the apoptotic activity of the two most active compounds revealed that compounds 16 and 26 could induce both the early and the late apoptosis of HePG2. Further mechanistic study of the HePG2 cell cycle confirmed the spectacular cytotoxic and apoptotic effects of both compounds. Compounds 16 and 26 showed a pronounced increase in cells in G2/M and Pre G1 phases with a concomitant reduction of cells in G0-G1 and S phases. A follow up enzymatic assay indicated that these two compounds have comparable activities with that of bromosporine as PCAF inhibitors with IC50 values of 8.13 and 5.31 muM respectively. Moreover, molecular docking study for all the synthesized compounds was performed to predict their binding affinities toward the active site of histone acetyltransferase GCN5. Results of molecular docking were strongly correlated with that of the cytotoxicity study.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N18 – PubChem

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Anticancer evaluation and docking study of new bifunctional phthalazine derivatives

Aims and Objective: A series of novel phthalazine derivatives was synthesized with versatile, readily accessible electrophilic and nucleophilic reagents. The newly synthesized compounds were confirmed by the results of spectroscopic measurements. Hence, their potential clinical application investigated in particular for cancer treatment. Materials and Methods: The newly synthesized compounds were characterized by spectroscopic measurements and were tested for their in vitro anticancer activity by MTT assay against human liver cancer cell line. Docking study of all the synthesized compounds was performed within the active site of the enzyme VEGFR-2 (Vascular Endothelial Growth Factor Receptor-2). Results: The quinazoline derivative 12 emerged as the most potent compound in this study with an IC50 value of 5. 4 muM. Docking study showed that the synthesized compounds were fit in the VEGFR-2 active site almost at the same position of sorafenib and vatalanib with comparable docking scores (-15.20 to -8.92 was kcal/mol). Conclusion: we have synthesized a novel series of phthalazine derivatives and evaluated their potential anticancer activity against HEPG2 cell line. The quinazoline derivative 12 emerged as the most potent compound in this study with an IC50 value of 5.4 muM. The SAR and docking studies pointed out that rigidification of the structure resulted in better activity and better binding within the active site of VEGFR-2 as in compounds 3, 5, 6 and 12. These results introduced new phthalazine derivatives having promising activity which could lead to the development of more potent anticancer agents.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N139 – PubChem

Discovery of 253-52-1

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Non-precious metals catalyze formal [4 + 2] cycloaddition reactions of 1,2-diazines and siloxyalkynes under ambient conditions

Copper(I) and nickel(0) complexes catalyze the formal [4 + 2] cycloaddition reactions of 1,2-diazines and siloxyalkynes, a reaction hitherto best catalyzed by silver salts. These catalysts based on earth abundant metals are not only competent, but the copper catalyst, in particular, promotes cycloadditions of pyrido[2,3-d]pyridazine and pyrido[3,4-d]pyridazine, enabling a new synthesis of quinoline and isoquinoline derivatives, as well as the formal [2 + 2] cycloaddition reaction of cyclohexenone with a siloxyalkyne.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N425 – PubChem

Brief introduction of 253-52-1

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Three Queries about the HOMA Index

HOMA (Harmonic Oscillator Model of Aromaticity) is a simple, successful, and widely used geometrical aromaticity index. However, HOMA can also be used as a general molecular descriptor appropriate for any type of molecule. It reaches the global maximum for benzene, whereas the potent magnetic aromaticity NICS index has no lower or upper limits. Hence, questions arise and go beyond mere differences between the geometric and magnetic aspects of aromaticity: (1) Does a molecule of aromaticity greater than that of benzene, but undisclosed by the HOMA definition, exist? (2) Can the Kekulene cyclohexatriene moiety with HOMA = 0 exist as a part of a larger system? (3) Can the geometrical aromaticity index be defined better? Our answer to the first query is “It is not likely enough”, to the second, “Why not define HOMA using a less mysterious molecule than cyclohexatriene?”, and to the third, “It is possible to construct another fair geometrical index, but is it better for evaluating aromaticity?” To find these answers, we have studied: (1) the HOMA and NICS indices of over 50 hexahomosubstituted benzenes, (2) the HOMA, as well as EN and GEO, indices of over 100 triply fused hexasubstituted benzenes, and (3) the HOMA and new Geometrical Auxiliary Index (GAI), of different unsaturated and saturated, aromatic and aliphatic hydrocarbons including all alkane constitutional isomers composed of up to nine carbon atoms.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N125 – PubChem

Extended knowledge of 253-52-1

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Green oxidant H2O2 as a hydrogen atom transfer reagent for visible light-mediated Minisci reaction

A visible light-mediated “green” protocol for metal-free oxidative coupling of heteroarenes and aliphatic C-H components has been achieved via a radical pathway. This cross-dehydrogenative coupling method features a broad scope of substrates. The green oxidant H2O2 is used as a hydrogen atom transfer reagent, which is environmentally benign, low cost, and atom economical.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N513 – PubChem