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ROS-Activated Compounds as Selective Anti-Cancer Therapeutics

Provided are compounds according to the following Formula I: The Formula I compounds are activated in the presence of reactive oxygen species (ROS) and are therefore selective anti-cancer therapeutics for cancers associated with elevated ROS. Also provided are methods and pharmaceutical compositions for treating cancers associated with increased ROS.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Synthesis and in vitro antimalarial testing of neocryptolepines: SAR study for improved activity by introduction and modifications of side chains at C2 and C11 on indolo[2,3-b]quinolines

To obtain a high antimalarial activity with neocryptolepine derivatives, modifying and changing the side chains at the C11 position with varying the substituents of an electron-withdrawing or electron-donating nature at the C2 position for a SAR study were executed. Installation of alkylamino and omega-aminoalkylamino groups at the C11 position of the neocryptolepine core was successful. For further variation, the aminoalkylamino substituents were transformed into the corresponding acyclic or cyclic carbamides or thiocarbamides. These side chain modified neocryptolepine derivatives were tested for antimalarial activity against CQR (K1) and CQS (NF54) of Plasmodium falciparum in vitro and for cytotoxicity toward mammalian L6 cells. Among the tested compounds, the compound 17f showed an IC50 of 2.2 nM for CQS (NF54) and a selectivity index of 1400, and 17i showed an IC50 of 2.2 nM for CQR (K1), a selectivity index of 1243, and a resistance index of 0.5.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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The first intermolecular interrupted imino-Nazarov reaction: Expeditious access to carbocyclic nucleoside analogues

The analogous imino-variant of the Nazarov reaction suffers from unfavorable energetics associated with the ring closure process, thereby limiting the utility of this class of reactions. In this report, the realization of the first intermolecular interrupted imino-Nazarov reaction utilizing silylated pyrimidine derivatives as nucleophilic trapping partners culminated in an expedient synthetic route to carbocyclic nucleoside analogues. The potential application of silylated nucleobases to intercept the oxyallyl cation in other variants of the Nazarov reaction provides vast opportunities to develop new strategies for the formation of carbocyclic nucleoside analogues.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Thermodynamics of various F420 coenzyme models as sources of electrons, hydride ions, hydrogen atoms and protons in acetonitrile

32 F420 coenzyme models with alkylation of the three different N atoms (N1, N3 and N10) in the core structure (XFH-) were designed and synthesized and the thermodynamic driving forces (defined in terms of the molar enthalpy changes or the standard redox potentials in this work) of the 32 XFH- releasing hydride ions, hydrogen atoms and electrons, the thermodynamic driving forces of the 32 XFH releasing protons and hydrogen atoms and the thermodynamic driving forces of XF- releasing electrons in acetonitrile were determined using titration calorimetry and electrochemical methods. The effects of the methyl group at N1, N3 and N10 and a negative charge on N1 and N10 atoms on the six thermodynamic driving forces of the F420 coenzyme models and their related reaction intermediates were examined; the results show that seating arrangements of the methyl group and the negative charge have remarkably different effects on the thermodynamic properties of the F420 coenzyme models and their related reaction intermediates. The effects of the substituents at C7 and C8 on the six thermodynamic driving forces of the F420 coenzyme models and their related reaction intermediates were also examined; the results show that the substituents at C7 and C8 have good Hammett linear free energy relationships with the six thermodynamic parameters. Meanwhile, a reasonable determination of possible reactions between members of the F420 family and NADH family in vivo was given according to a thermodynamic analysis platform constructed using the elementary step thermodynamic parameter of F420 coenzyme model 2FH- and NADH model MNAH releasing hydride ions in acetonitrile. The information disclosed in this work can not only fill a gap in the chemical thermodynamics of F420 coenzyme models as a class of very important organic sources of electrons, hydride ions, hydrogen atoms and protons, but also strongly promote the fast development of the chemistry and applications of F420 coenzyme.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Synthesis of indoxylic acid esters by rhodium-catalyzed carbene n-h insertion and thermal cyclization

Reaction between diethyl diazomalonate and a range of N-alkylanilines in the presence of a catalytic amount of rhodium(ii) acetate dimer afforded carbene N-H insertion to produce anilinomalonates in modest-to-good yields. Upon heating to a high temperature for a short time, the anilinomalonates underwent thermal cyclization to indoxylic acid esters.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

Awesome Chemistry Experiments For 5-(4-Hydroxyphenyl)isoxazole-3-carboxylic acid

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Sustainable heterogeneous platinum catalyst for direct methylation of secondary amines by carbon dioxide and hydrogen

Pt and MoOx co-loaded TiO2 is found to be highly effective for direct methylation of aliphatic and aromatic secondary amines by CO2 and H2 under solvent-free conditions. This is the first additive-free and reusable heterogeneous catalytic system with acceptable turnover number. Over and over: A heterogeneous Pt catalyst for direct methylation of aromatic amines by CO2 and H2 with high reusability and an order of magnitude higher turnover number than previous catalysts has been demonstrated (see scheme).

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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METHODS OF AMINATION

A method of synthesising a compound of formula I: comprising the step of reacting a moiety of formula II: with a moiety of formula III: in compressed carbon dioxide in the presence of a transition metal catalyst and a base, wherein L is a labile leaving group; RN1 is optionally substituted C5-20 aryl; RN2is selected from optionally substituted C5-20aryl, optionally substituted C3-20 heterocyclyl, optionally substituted C3-7 alkyl, and optionally substituted sulfonyl; RN3 is selected from H and optionally substituted C1-7 alkyl, C3-20 heterocyclyl and C5-20aryl; or RN2 and RN3 together with the nitrogen atom to which they are attached form optionally substituted nitrogen-containing C3-20heterocylyl or C5-20 heteroaryl; and R1 R2 and R3 are independently selected from optionally substituted C1-7alkyl, C5-20 aryl, C3-20 heterocyclyl, hydroxy, halo, amino and C1-7 alkoxy, or two of R1, R2 and R3, together with the silicon atom to which they are attached, may form a silicon containing C5-7 heterocyclyl group.

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Regioselective Nitration of N-Alkyl Anilines using tert-Butyl Nitrite under Mild Condition

Regioselective ring nitration of N-alkyl anilines is reported using tert-butyl nitrite. The reactions proceed efficiently with a wide range of substrates providing synthetically useful N-nitroso N-alkyl nitroanilines in excellent yields which can be easily converted into N-alkyl phenylenediamines and N-alkyl nitroanilines using Zn-AcOH and HCl/MeOH, respectively.

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Isoxazole – Wikipedia,
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Synthesis of 2-oxindoles via ‘transition-metal-free’ intramolecular dehydrogenative coupling (IDC) of sp2 C-H and sp3 C-H bonds

The synthesis of a variety of 2-oxindoles bearing an all-carbon quaternary center at the pseudo benzylic position has been achieved via a ‘transition-metal-free’ intramolecular dehydrogenative coupling (IDC). The construction of 2-oxindole moieties was carried out through formation of carbon-carbon bonds using KOt-Bu-catalyzed one pot C-alkylation of beta-N-arylamido esters with alkyl halides followed by a dehydrogenative coupling. Experimental evidences indicated toward a radical-mediated path for this reaction.

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Isoxazole – Wikipedia,
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LDA-promoted decomposition of benzenesulfenamides. A route to aminyl radicals by dioxygen oxidation of lithium amides

The LDA-promoted decomposition of N-monosubstituted sulfenamides 1a-d occurs through the formation of thioaminyl anions, which undergo oxidation either at sulfur, with formation of sulfonamides, or at nitrogen, with formation of thioaminyl radicals, depending on the nature of the 4′-substituent. The reaction of N,N-disubstituted sulfenamides 1e-h proceeds through the intermediacy of a lithium complex capable of generating aminyl radicals via sulfenyl group transfer to the di-iso-propylamido anion and subsequent aerial oxidation of the resulting lithium amides 3e-h.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem