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New preclinical development of a c-met inhibitor and its combined anti-tumor effect in c-met-amplified NSCLC

c-Met is a receptor tyrosine kinase with no commercially available product despite being a pivotal target in cancer progression. Unlike other c-Met inhibitors that fail clinically, ABN401 is a newly synthesized c-Met inhibitor that is not potentially degraded by aldehyde oxidase (AO) in human liver cytosol. This study aimed to determine the physicochemical stability, pharmacokinetics in beagle dogs, and therapeutic effect of ABN401 in a c-Met-amplified non-small-cell lung cancer (NSCLC) patient-derived xenograft (PDX) model. ABN401 was found to be a weak basic compound, with pKa and log P values of 7.49 and 2.46, respectively. It is poorly water-soluble but soluble at acidic pH. The accelerated storage stability is dependent on temperature, but the purity remains at over 97% after 6 months. The bioavailability is approximately 30% in dogs and it is highly efficient in the PDX model, achieving around 90% tumor growth inhibition in combination with erlotinib. These observations indicate that the compound is acceptable for the next phase of trials.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N110 – PubChem

Properties and Exciting Facts About Phthalazine

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Organocatalytic diastereo- and enantioselective annulation reactions – Construction of optically active 1,2-dihydroisoquinoline and 1,2-dihydrophthalazine derivatives

(Chemical Equation Presented) Good to high conversions (70-100%) into optically active tri- or tetracyclic nitrogen-containing compounds 1 based on 1,2-dihydroisoquinolines and 1,2-dihydro-phthalazines proceed with high diastereoselectivity (d.r. ? 15:1) and good to excellent enantioselectivity (85-96% ee) in the presence of a chiral amine.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N153 – PubChem

Properties and Exciting Facts About Phthalazine

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Boron Trifluoride-Assisted Ziegler-Zeiser Reaction of Perfluoroalkyllithiums. An Efficient Synthesis of Perfluoroalkylated Heterocycles

Quinoline, isoquinoline, quinaldine, phthalazine, and quinoxaline are all found to react smoothly with perfluoroalkyllithiums in the presence of BF3*OEt2, giving the corresponding perfluoroalkyllithium addition and/or substitution products in good yields.Perfluoroalkylation occurs at the carbon atom next to the nitrogen.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N454 – PubChem

Discovery of 253-52-1

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Short-lived excited triplet states studied by time-resolved EPR spectroscopy

In this review, we present an overview of the application of time-resolved electron paramagnetic resonance (TREPR) to the study of excited triplet states. After a brief discussion of background and experimental methods, triplet properties clarified by TREPR are reviewed to show how TREPR provides rich information about electronic and molecular structures and dynamic properties of the lowest excited triplet states. The review includes discussion of the properties of non-phosphorescent triplet states, various interactions (configurational, vibronic and spin-orbit) and triplet properties, molecular distortions, and triplet states related to excited-state proton transfer. For each topic, typical examples are taken mainly from work carried out in the authors’ laboratories in Kyoto and Sendai over the last two decades. Finally, recent new advances are reviewed briefly by focusing attention on two topics: excited triplet states in liquid solution and multiplet excited states generated by triplet-radical interactions.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N184 – PubChem

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N,N-coupled heterobicycles from cyclic hydrazine derivatives. Part 8: Synthesis of 3-imino substituted 1-thioxo-2,3,5,10-tetrahydro-[1,2,4]triazolo[1,2-b]phthalazines and 1-thioxo-5,10-dihydro-[1,3,4]thiadiazolo[3,4-b]phthalazines

The preparation of the mostly 3-arylimino substituted derivatives 4 of the hitherto unknown [1,3,4]thiadiazolo[3,4-b]phthalazine ring system succeeded by treatment of the related 2-thiocarbamoyl-1,2,3,4-tetrahydrophthalazines 2 with thiophosgene under mild conditions. The reaction of the 2 with arylisothiocyanates under heating yields the 2-aryl-1-thioxo-3-arylimino[1,2,4]triazolo[1,2-b]phthalazines 5.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N296 – PubChem

Awesome Chemistry Experiments For 6-Amino-2,3-dihydrophthalazine-1,4-dione

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Selective synthesis and photoluminescence study of pyrazolopyridopyridazine diones and N-aminopyrazolopyrrolopyridine diones

The newly designed luminol structures of pyrazolopyridopyridazine diones and N-aminopyrazolopyrrolopyridine diones were synthesized from versatile 1,3-diaryfuropyrazolopyridine -6,8-diones, 1,3-diarylpyrazolopyrrolopyridine-6,8-diones, or 1,3-diaryl-7- methylpyrazolopyrrolopyridine -6,8-diones with hydrazine monohydrate. Photoluminescent and solvatofluorism properties containing UV-Vis absorption, emission spectra, and quantum yield (Phif) study of pyrazolopyridopyridazine diones and N-aminopyrazolopyrrolopyridine diones were also studied. Generally, most of pyrazolopyrrolopyridine-6, 8-diones 6 exhibited the significant fluorescence intensity and the substituent effect when compared with N-aminopyrazolopyrrolopyridine diones, particularly for 6c and 6j with a m-chloro group. Additionally, the fluorescence intensity of 6j was significantly promoted due to the suitable conjugation conformation. Based on the quantum yield (Phif) study, the value of compound 6j (0.140) with planar structural skeletal was similar to that of standard luminol (1, 0.175).

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N647 – PubChem

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Elucidation of the Mechanism of Silver-Catalyzed Inverse Electron-Demand Diels-Alder (IEDDA) Reaction of 1,2-Diazines and Siloxy Alkynes

Density functional theory (DFT) calculations were utilized to reveal the effect of highly efficient transition metal catalysis in inverse electron demand Diels-Alder (IEDDA) reactions. The silver-catalyzed IEDDA reactions of 1,2-diazines and siloxy alkynes were investigated to highlight the effect of the catalyst and its mode of action. Two different reaction pathways, concerted and stepwise, were explored as well as the uncatalyzed reaction. Computations elucidate the details of the highly efficient Ag catalyst in IEDDA reaction, and are consistent with previous experimental studies. The mode of action for the catalyst is fully revealed and its specific effect on the regioselectivity/specificity of the reaction is established.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N45 – PubChem

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Merozoite surface protein 1 from plasmodium falciparum is a major target of opsonizing antibodies in individuals with acquired immunity against malaria

Naturally acquired immunity against malaria is largely mediated by serum antibodies controlling levels of blood-stage parasites. A limited understanding of the antigenic targets and functional mechanisms of protective antibodies has hampered the development of efficient malaria vaccines. Besides directly inhibiting the growth of Plasmodium parasites, antibodies can opsonize merozoites and recruit immune effector cells such as monocytes and neutrophils. Antibodies against the vaccine candidate merozoite surface protein 1 (MSP-1) are acquired during natural infections and have been associated with protection against malaria in several epidemiological studies. Here we analyzed serum antibodies from semi-immune individuals from Burkina Faso for their potential (i) to directly inhibit the growth of P. falciparum blood stages in vitro and (ii) to opsonize merozoites and to induce the antibody-dependent respiratory burst (ADRB) activity of neutrophils. While a few sera that directly inhibited the growth of P. falciparum blood stages were identified, immunoglobulin G (IgG) from all individuals clearly mediated the activation of neutrophils. The level of neutrophil activation correlated with levels of antibodies to MSP-1, and affinity-purified MSP-1-specific antibodies elicited ADRB activity. Furthermore, immunization of nonhuman primates with recombinant full-size MSP-1 induced antibodies that efficiently opsonized P. falciparum merozoites. Reversing the function by preincubation with recombinant antigens allowed us to quantify the contribution of MSP-1 to the antiparasitic effect of serum antibodies. Our data suggest that MSP-1, especially the partially conserved subunit MSP-183, is a major target of opsonizing antibodies acquired during natural exposure to malaria. Induction of opsonizing antibodies might be a crucial effector mechanism for MSP-1-based malaria vaccines.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N576 – PubChem

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Organometallic complexes of functionalized chelating azines

Organometallic compounds of the chelating azines containing carbonyl, hydroxyl, thiol, selenol, amino, imino, phosphino, thienyl, indolyl, carbazolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, and N-heterocyclic carbene functionalities are reviewed. Synthesis and coordination modes, the role of the discussed compounds in catalysis, materials chemistry, photochemistry, and microbiology are highlighted.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N378 – PubChem

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Identification of Intact Lipid Peroxides by Ag+ Coordination Ion-Spray Mass Spectrometry (CIS-MS)

Free radical-induced autoxidation of lipids containing polyunsaturated fatty acids (PUFA) has been implicated in numerous human diseases including atherosclerosis, neurodegenerative diseases, and cancer. Autoxidation of PUFAs generates hydroperoxides as primary oxidation products and further oxidation leads to cyclic peroxides as secondary oxidation products. It is challenging to identify these peroxides by conventional electro-spray ionization (ESI) mass spectrometry (MS) method because of their thermal and chemical instability under most analytical conditions. Ag+ coordination ion-spray CIS-MS has proven to be a powerful tool to analyze these intact lipid peroxides. Ag+ preferentially complexes with the double bonds and induces characteristic fragmentation in the gas phase. Monocyclic peroxides, bicyclic endoperoxides, serial cyclic peroxides, and dioxolane-isoprostane peroxides have been identified from the oxidation of cholesteryl arachidonate and phospholipids containing arachidonate. This technique has been widely used for structural identification but it is difficult to make it a quantitative tool because of the formation of multiple silver adducts.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N662 – PubChem