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Alcohols as alkylating agents in heteroarene C-H functionalization

Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage. One of the core principles underlying DNA biosynthesis is the radical-mediated elimination of H2O to deoxygenate ribonucleotides, an example of ‘spin-centre shift’, during which an alcohol C-O bond is cleaved, resulting in a carbon-centred radical intermediate. Although spin-centre shift is a well-understood biochemical process, it is underused by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylation reactions using alcohols as radical precursors. Because conventional radical-based alkylation methods require the use of stoichiometric oxidants, increased temperatures or peroxides, a mild protocol using simple and abundant alkylating agents would have considerable use in the synthesis of diversely functionalized pharmacophores. Here we describe the development of a dual catalytic alkylation of heteroarenes, using alcohols as mild alkylating reagents. This method represents the first, to our knowledge, broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer catalysis. The value of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N213 – 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, Application In Synthesis of 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

Insertion of Isocyanides into N?Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds

Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide-based reactions, which then proceed through a key insertion of the isocyanide into a N?Si bond. The reaction is initiated by N activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert-type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N?Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of alpha-substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosoma brucei and T. cruzi, featuring favorable drug-like properties and safety profiles.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N238 – PubChem

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Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. Application In Synthesis of 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.

One of the major reasons for studying chemical kinetics is to use measurements of the macroscopic properties of a system, Application In Synthesis of 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

1,3-Dipolar Cycloaddition of Ylides Generated from Diazines and Dichlorocarbene

Reaction of dichlorocarbene with diazines in the presence of dimethyl maleate and dimethyl acetylenedicaroxylate involves intermediate formation of ylides, namely cycloimmoniodichloromethanides, followed by 1,3-dipolar cycloaddition of the latter to dipolarophiles. This carbene-ylide sequence was used to synthesize chloro-substituted pyrrolo[1,2-6]pyridazines, pyrrolo[1,2-c]- and pyrrolo[1,2-a]pyrimidines, pyrrolo[1,2-a]phthalazine, pyrrolo[1,2-a]-, pyrrolo[1,2-c]-, and pyrrolo[2,1-b]quinazolines, pyrrolo[1,2-a]-quinoxalines, and pyrrolo[1,2-a]naphthiridines. The cycloaddition is stereo- and regioselective, which suggests a concerted reaction mechanism. The regioselectivity of the cycloaddition is correctly predicted in terms of the PMO theory on the basis of MNDO electronic parameters of halogenated cycloimmonium ylides.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N234 – PubChem

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2-METHYLMORPHOLINE PYRIDO-, PYRAZO- AND PYRIMIDO-PYRIMIDINE DERIVATIVES AS MTOR INHIBITORS

There is provided a compound of Formula (I), or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula (1), and the use of a compound of Formula (1) as a medicament and in the treatment of cancer

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Phthalazine – Wikipedia,
Phthalazine | C8H6N706 – PubChem

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L-4, a well-tolerated and orally active inhibitor of hedgehog pathway, exhibited potent anti-tumor effects against medulloblastoma in vitro and in vivo

Inhibition of aberrant Hedgehog (Hh) pathway had been proved to be a promising therapeutic intervention in cancers like basal cell carcinoma (BCC), medulloblastoma (MB), and so on. Two drugs (Vismodegib, Sonidegib) were approved to treat BCC and more inhibitors are in clinical investigation. However, the adverse effects and drug resistance restricted the use of Hh inhibitors. In the present study, 61 synthesized compounds containing central backbone of phthalazine or dimethylpyridazine were screened as candidates of new Hh signaling inhibitors by performing dual luciferase reporter assay. Among the compounds, L-4 exhibited an IC50 value of 2.33 nM in the Shh-Light II assay. L-4 strongly inhibited the Hh pathway in vitro and blocked the Hh pathway by antagonizing the smoothened receptor (Smo). Remarkably, L-4 could significantly suppress the Hh pathway activity provoked by Smo mutant (D473H) which showed strong resistant properties to existing drugs such as Vismodegib. Orally administered L-4 exhibited prominent dose-dependent anti-tumor efficacy in vivo in Ptch+/-; p53-/- MB allograft model. Furthermore, L-4 showed good tolerance in acute toxicity test using ICR mice. These evidences indicated that L-4 was a potent, well-tolerated, orally active inhibitor of Hedgehog pathway, and might be a promising candidate in development of Hh-targeted anti-cancer drugs.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N515 – PubChem

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Phthalazine-triones: Calix[4]arene-assisted synthesis using green solvents and their anticancer activities against human cancer cells

Fourteen phthalazine-triones bearing different substituents at C-4 position were synthesized through multicomponent reactions (MCR) by using phthalhydrazide, dimedone and diferent aldehydes as starting materials, p-sulfonic acid calix[4]arene as catalyst and ethyl lactate as solvent under microwave irradiation. Compounds 7?16 were obtained in excellent to moderate yields (94?51%) in only 10 min of reaction using this methodology. The antiproliferative activity against cancer cells was disclosed, for the first time, for synthesized compounds. The capacity of all compounds to inhibit cancer cells growth was dependent on the histological origin of cells. Compound 20 was active against more than one strain.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N361 – PubChem

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Heterocyclic Nanographenes and Other Polycyclic Heteroaromatic Compounds: Synthetic Routes, Properties, and Applications

Two-dimensionally extended, polycyclic heteroaromatic molecules (heterocyclic nanographenes) are a highly versatile class of organic materials, applicable as functional chromophores and organic semiconductors. In this Review, we discuss the rich chemistry of large heteroaromatics, focusing on their synthesis, electronic properties, and applications in materials science. This Review summarizes the historical development and current state of the art in this rapidly expanding field of research, which has become one of the key exploration areas of modern heterocyclic chemistry.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N419 – PubChem

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Application of 253-52-1, Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Article, and a compound is mentioned, 253-52-1, Phthalazine, introducing its new discovery.

Hydrogen-bonded structures of the isomeric compounds of phthalazine with 3-chloro-2-nitro-benzoic acid, 4-chloro-2-nitro-benzoic acid and 4-chloro-3-nitro-benzoic acid

The structures of three isomeric compounds, C7H 4ClNO4¡¤C8H6N2, of phthalazine with chloro-and nitro-substituted benzoic acid, namely, 3-chloro-2-nitro-benzoic acid-phthalazine (1/1), (I), 4-chloro-2-nitro-benzoic acid-phthalazine (1/1), (II), and 4-chloro-3-nitro-benzoic acid-phthalazine (1/1), (III), have been determined at 190 K. In the asymmetric unit of each compound, there are two crystallographically independent chloro-nitro-benzoic acid-phthalazine units, in each of which the two components are held together by a short hydrogen bond between an N atom of the base and a carboxyl O atom. In one hydrogen-bonded unit of (I) and in two units of (II), a weak C-H…O inter-action is also observed between the two components. The N…O distances are 2.5715 (15) and 2.5397 (17) A for (I), 2.5655 (13) and 2.6081 (13) A for (II), and 2.613 (2) and 2.589 (2) A for (III). In both hydrogen-bonded units of (I) and (II), the H atoms are each disordered over two positions with (N site):(O site) occupancies of 0.35 (3):0.65 (3) and 0.31 (3):0.69 (3) for (I), and 0.32 (3):0.68 (3) and 0.30 (3):0.70 (3) for (II). The H atoms in the hydrogen-bonded units of (III) are located at the O-atom sites.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N170 – PubChem

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Synthesis, structure, and in vitro anticancer activity of new polycyclic 1,2-diazines

The synthesis, structure, and in vitro anticancer activity of a new class of anticancer derivatives with dihydrobenzo[5,6]isoindolo[1,2-A]phthalazine and dihydrobenzo[f]pyridazino[6,1-A]isoindole skeletons are presented. The preparation is straight and efficient, involving two steps only: a N-Alkylation of the pyridazine or phthalazine heterocycle, followed by a [3 + 2] dipolar cycloaddition of 1,2-diazinium ylides to the corresponding dipolarophiles. The synthesis was performed under microwave and ultrasound (US) irradiation as well as under conventional thermal heating. The most effective conditions in term of yields and time were found to be US irradiation. The penta- and tetra-cyclic 1,2-diazines were evaluated for their in vitro anticancer activity. The pentacyclic 1,2-diazine derivatives exhibit a significant anticancer activity against Non-Small Cell Lung Cancer NCI-H460, Leukemia MOLT-4, Leukemia CCRF-CEM, and Breast Cancer MCF7. A feasible explanation for anticancer efficiency of the pentacyclic 1,2-diazines have been furnished, being correlated with the mechanisms of action. Graphical Abstract: The synthesis (conventional thermal heating, microwave and ultrasound irradiation), structure, and in vitro anticancer activity of a new class of anticancer molecules with polycyclic 1,2-diazines skeleton is presented.[Figure not available: see fulltext.]

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N278 – PubChem

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Neutrophil NET formation is regulated from the inside by myeloperoxidase-processed reactive oxygen species

Aim Neutrophil extracellular traps (NETs) are mesh-like DNA fibers clad with intracellular proteins that are cast out from neutrophils in response to certain stimuli. The process is thought to depend on reactive oxygen species (ROS) generated by the phagocyte NADPH-oxidase and the ROS-modulating granule enzyme myeloperoxidase (MPO), but when, how, and where these factors contribute is so far uncertain. The neutrophil NADPH-oxidase can be activated at different cellular sites and ROS may be produced and processed by MPO within intracellular granules, even in situations where a phagosome is not formed, e.g., upon stimulation with phorbol myristate acetate (PMA). Objectives We investigated the subcellular location of ROS production and processing by MPO in the context of PMA-induced NET formation. Results Complete neutralization of extracellular ROS was not sufficient to block NET formation triggered by PMA, indicating that intragranular ROS are critical for NETosis. Employing a set of novel MPO-inhibitors, inhibition of NET formation correlated with inhibition of intragranular MPO activity. Also, extracellular addition of MPO was not sufficient to rescue NET formation in completely MPO-deficient neutrophils and specific neutralization by luminol of MPO-processed ROS within intracellular granules led to a complete block of PMA-triggered NET formation. Conclusion We show for the first time that inhibition of intragranular MPO activity, or neutralization of intragranular MPO-processed ROS by luminol effectively block NET formation. Our data demonstrate that ROS must be formed and processed by MPO in order to trigger NET formation, and that these events have to occur within intracellular granules.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N529 – PubChem