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Multidrug resistance (MDR) is a major limiting factor in the development and application of drug candidates. MDR caused by MRP-1 is known to be modulated by the nonsteroidal antiinflammatory drug indomethacin. We have synthesized and biologically evaluated a library of indomethacin analogues. The indomethacin-derived compound library was synthesized employing the Fischer-indole synthesis as the key transformation and making use of a “resin-capture-release” strategy. Sixty representative members of the library were evaluated in a cell biological cytotoxicity assay employing the MRP-1 expressing human glioblastoma cell line T98G as a model system. Nine of the 60 tested derivatives increased the doxorubicin-mediated cytotoxicity at a comparable or higher level than indomethacin itself. Analysis of these derivatives revealed an interesting structure-function relationship. Most remarkably, two substances increased the toxicity, when doxorubicin was used at clinically relevant low concentrations, at a higher degree than indomethacin.

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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

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A catalyst don’t appear in the overall stoichiometry of the reaction it catalyzes, COA of Formula: C20H18ClNO4, but it must appear in at least one of the elementary reactions in the mechanism for the catalyzed reaction. 1601-18-9, Name is Methyl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate, molecular formula is C20H18ClNO4. In a Article, authors is Zhou, Yuxiang,once mentioned of 1601-18-9

An efficient cobalt-catalyzed C2alpha selective C(sp3)-H acyloxylation of 2-substituted indoles with tert-butyl peresters to synthesize diverse 2alpha-acyloxylated indole derivatives is described. This newly developed method exhibits mild conditions, low-cost catalyst, and high functional group compatibility. In addition, the effectiveness of this chemistry is illuminated by a late-stage modification of methylated indomethacin.

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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

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Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 1601-18-9, molcular formula is C20H18ClNO4, introducing its new discovery. category: indole-building-block

Synthesis of a range of indomethacin analogues, required for investigation in combination toxicity assays, bearing both N-benzyl and N-benzoyl groups, is described. Copyright

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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

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In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 1601-18-9, name is Methyl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate, introducing its new discovery. Recommanded Product: 1601-18-9

A readily accessible and bench-stable water-soluble hypervalent iodine(III) reagent (phenyliodonio)sulfamate (PISA) with an I-N bond was synthesized, and its structure was characterized by X-ray crystallography. With PISA, various indoles were synthesized via C-H amination of 2-alkenylanilines involving an aryl migration/intramolecular cyclization cascade with excellent regioselectivity in aqueous CH3CN. Notably, using this new method as the key step, not only two drug molecules, indometacin and zidometacin, but also another bioactive molecule, pravadoline, were synthesized.

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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

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Cyclooxygenase inhibitors include compounds of the formula: where R represents phenyl, nitrophenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 3,4-dimethoxyphenyl, 2-methoxyphenyl, 4-hydroxyphenyl, dimethylaminophenyl, 3-methoxyphenyl, 4-ethoxyphenyl, 2,4,5-trimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2,4,6-trimethoxyphenyl, and 2,4-dimethoxyphenyl, 3-hydroxyphenyl, 4-dimethylaminophenyl, or 2,3,4-trimethoxyphenyl.

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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

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Several iridium complexes [Ircod)L2]X (L = phosphine ligand) were used as precatalysts for the exchange labeling of a range of model compounds with deuterium gas. Complexes with monodentate L (e.g. PMePh2, PPh3 and substituted derivatives thereof) catalyzed exchange selectively of hydrogens four bonds away from a coordinative heteroatom in the substrate, while those with bidentate L (bis(diphenylphosphino)ethane (dppe) and bis(diphenylphosphino)butane) catalyzed exchange of hydrogens both four and five bonds away from a coordinative heteroatom. At heavier loadings, some monodentate complexes also catalyzed five-bond labeling of some substrates. [Ir(cod)(dppe)]BF4 catalyzed the tritium labeling of methyl 6-methoxynaphth-2-ylacetate at C1 and C3.

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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

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Heterocyclic sulfinates are effective reagents in palladium-catalyzed coupling reactions with aryl and heteroaryl halides, often providing high yields of the targeted biaryl. However, the preparation and purification of complex heterocylic sulfinates can be problematic. In addition, sulfinate functionality is not tolerant of the majority of synthetic transformations, making these reagents unsuitable for multistep elaboration. Herein, we show that heterocyclic allylsulfones can function as latent sulfinate reagents and, when treated with a Pd(0) catalyst and an aryl halide, undergo deallylation, followed by efficient desulfinylative cross-coupling. A broad range of allyl heteroarylsulfones are conveniently prepared, using several complementary routes, and are shown to be effective coupling partners with a variety of aryl and heteroaryl halides. We demonstrate that the allylsulfone functional group can tolerate a range of standard synthetic transformations, including orthogonal C- and N-coupling reactions, allowing multistep elaboration. The allylsulfones are successfully coupled with a variety of medicinally relevant substrates, demonstrating their applicability in demanding cross-coupling transformations. In addition, pharmaceutical agents crizotinib and etoricoxib were prepared using allyl heteroaryl sulfone coupling partners, further demonstrating the utility of these new reagents.

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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

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The stereochemistry around the N-benzoylated indole moiety of indometacin was studied by restricting the rotation about the N-C7? and/or C7?-C1? bond. In the 2?,6?-disubstituted ones, an atropisomeric property was found and the atropoisomers were separated and isolated as stable forms. Their biological abilities to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were examined. Only the aR-isomer showed specific inhibition of COX-1, and COX-2 was not inhibited by either atropisomer. Conformational analysis in NMR studies and X-ray crystallography, and CD spectra in combination with calculations were utilized to elucidate the bioactive conformations. Copyright

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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

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We report the screening of analogues of indomethacin to investigate the structure-activity relationship (SAR) of indomethacin-mediated multidrug resistance associated protein-1 (MRP-1) inhibition. By examining the activities of compounds with minor variations of the parent structure, we were able to separate MRP-1, glutathione-S-transferase (GST), cyclooxygenase (COX)-1 and COX-2 inhibitory activities. Combination cytotoxicity assays were utilised to identify agents which possess synergistic potential in MRP-1-expressing cell lines. MRP-1 Inside Out Vesicles (IOVs) were utilised to demonstrate the ability of the indomethacin analogues to inhibit the pump directly. Most of the indomethacin analogues active as MRP-1 inhibitors were poor GST inhibitors when compared with the GST-inhibitory activity of indomethacin. Two of the MRP-1 inhibitory analogues were found to have no COX-1 inhibitory activity and low COX-2 inhibitory activity, suggesting potentially reduced clinical toxicity. One MRP-1 inhibitory indomethacin analogue was also found to have low COX-1 inhibitory activity, but significant COX-2 inhibitory activity, making this analogue again interesting in terms of low potential toxicity, but with the possibility of direct inhibitory effects on tumour growth.

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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

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No migration? No problem! A series of new N-heterocyclic carbene based Pd complexes has been created and evaluated in the Negishi cross-coupling of aryl and heteroaryl chlorides, bromides, and triflates with a variety of secondary alkylzinc reagents (see scheme). The direct elimination product is nearly exclusively formed; in most examples there is no migratory insertion at all. Copyright

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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles