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A Rh(II)/Au(I) catalyzed carbene cascade approach for the stereoselective synthesis of diverse spirocarbocycles is described. The cascade reaction involves a rhodium carbene initiated sp2 C?H functionalization followed by a gold catalyzed Conia-ene cyclization. The cascade reaction accommodates a variety of aryl substituents as well as ring sizes and proceeds with high diastereoselectivity providing access to diverse spirocarbocycles. (Figure presented.).

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A recyclable catalytic system comprising magnetically separable CuFe 2O4 nanoparticles in a poly(ethylene glycol) medium has been established as an inexpensive, nontoxic, environmentally benign system for the amination of aryl iodides with aqueous ammonia. A wide variety of aryl iodides underwent amination to afford the corresponding aryl amines in moderate to good yields. The catalytic system was recycled five times with consistent activity. Georg Thieme Verlag Stuttgart . New York.

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A novel 1,7-palladiummigration-cyclization-dealkylation sequence for the regioselective synthesis of benzotriazoles has been developed. These reactions proceed in excellent yields with high regioselectivities. The mechanism of the reaction has also been investigated.

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A new cyclisation procedure to prepare 4-carboxy-quinolin-2-ones via a one-pot Cu(II)-mediated radical cross-dehydrogenative coupling/sulfinic acid elimination of linear anilides is described. Extensions to more complex substrates are also reported as are applications in target synthesis allowing access to natural products isolated from Oryza sativa and HOFQ.

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A palladium-catalyzed multicomponent reaction (MCR) involving aryne, CO, and aniline is established for straightforward assembly of a phenanthridinone scaffold through C-H bond activation. Free combination with multiple kinds of readily available anilines and arynes is facilely achieved for phenanthridinone construction without prefunctionalization. Representative natural products were subsequently synthesized through this MCR strategy highly efficiently. Control experiments and interval NMR tracking revealed the mechanism, particularly the key role of CuF2 in determining the aryne-releasing rate from the precursor in this transformation.

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Treatment of magnesium cyclopropylidenes, which were generated from 1-chlorocyclopropyl phenyl sulfoxides with isopropylmagnesium chloride in THF at -78 C, with N-lithio arylamines gave arylamines cyclopropylated at the 2-position in moderate to good yields. Use of the magnesium cyclopropylidenes having at least one substituent was found to be essential to this cyclopropylation. This procedure offers a novel synthesis of arylamines having a cyclopropane ring at the 2-position directly from arylamines.

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The present invention provides compounds of formula (I) (Formula (I)) and pharmaceutically acceptable salts thereof, wherein Q, X% X4,X5 X6, X7,R1, R2, R3 and R8 are as defined in the specification, processes for the preparation of such compounds, pharmaceutical compositions containing them and the use of such compounds in therapy.

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Ethyl bromodifluoroacetate (BrCF2COOEt) was first used as the N-formylating reagent in the copper-catalyzed N-formylation of amines. A range of primary, secondary, cyclic arylamines, and aliphatic amines underwent the N-formylation smoothly to furnish the N-formamides in moderate-to-excellent yields.

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Based on our previous results on the ascertained potent growth inhibition effect against a panel of 60 human tumors cell lines at National Cancer Institute of Bethesda (NCI), we have synthesized a novel series of thirty-one 2-[N-methyl(R-phenyl)-aminomethyl]-3-phenyl-7-trifluoromethylquinoxalines (1-31). The lead compound 1 was previously reported to be endowed with significant inhibition against hDHFR enzyme, with a Ki of 0.2 muM. Docking studies were performed on compound 1 and here reported to predict its binding conformation to human dihydrofolate reductase (hDHFR). All compounds (1-31) were assayed versus hDHFR and human thymidylate synthase (hTS). From the screening emerged that all compounds inhibited hDHFR with Ki values included between 0.2 and 11 muM, while only a few (6, 21, 24, 27, 29) showed great activity and selectivity towards hTS. Evaluation of the anticancer activity was performed by NCI, first against the three cell line panel, and only the most active compounds (17, 21, 24, 26, 27) were evaluated on a panel of 60 human tumor cell lines. Compound 21 was the most active against all cell lines with log GI50 equal to -5.49 and log LC50 equal to -4.19 and maintained significant percent of growth inhibition on seven cancer cell lines at the concentration of 1 muM. Compound 17 was the second most active and moreover showed interesting selectivity against some cell lines (Lung cancer: A549/ATCC, Melanoma: UACC-257, Ovarian Cancer: ovcar-8 and Renal cancer: RXF 393) at all concentration examined (100-0.01 muM).

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Compounds of formula (I) wherein R1, R2, R3, R4, R5, L1, L2, m, and n are as defined herein, are useful for the treatment or prophylaxis of conditions such as Duchenne muscular dystrophy, Becker muscular dystrophy, and cachexia.

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