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A new and facile AgSbF6-mediated protocol for the construction of C-4 thiolated or selenylated isoquinolin-1(2H)-ones via a radical pathway was established. This reaction proceeded efficiently with excellent regioselectivity, a broad substrate scope, and good functional group tolerance. A radical reaction mechanism involving thiyl radicals as key intermediates is proposed for the present transformation.

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Provided is a method for improving treatment of a neoplastic condition by combining a therapeutically effective amount of a polyADP-ribose polymerase inhibitor with a therapeutically effective amount of a compound which triggers the release of nucleolin from the G-quadruplexes in rDNA. As specifically exemplified, the compound which increases nucleolin binding is a substituted quinobenzoxazine analog, for example CX-3543.

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The invention relates to a 4 – substituted […] quinoline – 1 (2 H) – ketone compound, comprising the following steps: the raw material isoquinolin – 1 (2 H) – one and diaryl disulfide dissolved in dichloroethane, then adding hexafluoroantimonate acid silver, in the 60 – 140 C lower reaction 6 – 12 hours, after the reaction and the separation and purification of the crude product, to obtain the 4 – substituted […] quinoline – 1 (2 H) – ketone compound. The advantage of this method is: and is simple, the operation is simple and does not need nonaqueous harsh reaction conditions and the like, high yield, high selectivity, substrate and wide application range, preparation product easy purification. (by machine translation)

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The invention is selected, novel, and known analogs of isoquinolinones of the formula and pharmaceutically acceptable salts thereof; novel pharmaceutical compositions; and a method for enhancing the lethal effects for tumor cells to treatment having DNA damaging activity such as ionizing radiation or with chemotherapeutic agents.

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Approaches toward the preparative-scale synthesis of target 3,4-dihydro-1(2H)-isoquinolinones 1-3 are presented. Compounds 1 and 2 were prepared via a Schmidt rearrangement on easily obtained indanone precursors, but in low overall yield. A better method to make this class of compounds is exemplified by the large-scale synthesis of 2 via a Curtius rearrangement sequence. Thus, high-temperature thermal cyclization of an in situ formed styryl isocyanate from precursor 8 in the presence of tributylamine gave the corresponding 1(2H)-isoquinolinone (9). Catalytic hydrogenation of 9 provided the desired 3,4-dihydro-5-methyl-1(2H)-isoquinolinone (2) in 65 % overall yield. Similar reduction of a commercially available 5-hydroxy-1(2H)-isoquinolinone precursor 10 followed by an O-alkylation/amination sequence gave target 3 in good overall yield. The route proceeding via the Curtius rearrangement is recommended for large scale synthesis of other 3,4-dihydro-1(2H)-isoquinolinones. Only when deactivating substituents or sensitive functionality within the benzenoid ring render the high temperature ring closure of the intermediate isocyanate inefficient might a Schmidt rearrangement protocol be the method of choice.

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A new and facile AgSbF6-mediated protocol for the construction of C-4 thiolated or selenylated isoquinolin-1(2H)-ones via a radical pathway was established. This reaction proceeded efficiently with excellent regioselectivity, a broad substrate scope, and good functional group tolerance. A radical reaction mechanism involving thiyl radicals as key intermediates is proposed for the present transformation.

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A 4 – substituted quinoline -1 […] (2 H) – ketone compound preparation method (by machine translation)

The invention relates to a 4 – substituted […] quinoline – 1 (2 H) – ketone compound, comprising the following steps: the raw material isoquinolin – 1 (2 H) – one and diaryl disulfide dissolved in dichloroethane, then adding hexafluoroantimonate acid silver, in the 60 – 140 C lower reaction 6 – 12 hours, after the reaction and the separation and purification of the crude product, to obtain the 4 – substituted […] quinoline – 1 (2 H) – ketone compound. The advantage of this method is: and is simple, the operation is simple and does not need nonaqueous harsh reaction conditions and the like, high yield, high selectivity, substrate and wide application range, preparation product easy purification. (by machine translation)

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5-Nitrofuran-2-ylmethyl group as a potential bioreductively activated pro-drug system

5-Substituted isoquinolin-1-ones have been synthesised by one-pot Curtius rearrangement of the corresponding substituted 3-phenylpropenoyl azides and cyclisation. Arylmethylation of the anions of the isoquinolinones with benzyl halides [4-methoxybenzyl chloride, 2-(chloromethyl)furan and 5-nitro-2-(tosyloxymethyl)furan] takes place exclusively at nitrogen. Nitration of 2-(furan-2-ylmethyl)isoquinolin-1-one in strongly acidic medium gives 2-(5-nitrofuran-2-ylmethyl)isoquinolin-1-one, whereas weaker acidic conditions lead to dinitration. Curtius rearrangement of 3-carboranylbutanoyl azide and trapping with 5-nitrofuran-2-ylmethanol gives 5-nitrofuran-2-ylmethyl N-(3-carboranylpropyl)carbamate. Biomimetic reduction of these nitrofuranylmethyl derivatives of anticancer drugs triggers release of the parent drugs. Thus, these nitrofurans have potential applications as pro-drugs for selective release of therapeutic drugs in hypoxic solid tumours.

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Reference£º
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem