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Potent, 1H-pyrazolo[3,4-b]pyridine-containing inhibitors of the human nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using structure-based design techniques. Many of these compounds exhibited nanomolar antiproliferation activities against human tumor lines in in vitro cell culture experiments, and a representative example (compound 26) demonstrated encouraging in vivo efficacy in a mouse xenograft tumor model derived from the A2780 cell line. This molecule also exhibited reduced rat retinal exposures relative to a previously studied imidazo-pyridine-containing NAMPT inhibitor. Somewhat surprisingly, compound 26 was only weakly active in vitro against mouse and monkey tumor cell lines even though it was a potent inhibitor of NAMPT enzymes derived from these species. The compound also exhibited only minimal effects on in vivo NAD levels in mice, and these changes were considerably less profound than those produced by an imidazo-pyridine-containing NAMPT inhibitor. The crystal structures of compound 26 and the corresponding PRPP-derived ribose adduct in complex with NAMPT were also obtained.

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The molar standard enthalpy of formation in condensed and gas phases of indazole, 1H-indazole-3-carboxylic acid, 1H-indazole-5-carboxylic acid, 1H-indazole-6-carboxylic acid and 1-methyl-1H-indazole-6-carboxylic methyl ester is reported. These properties were obtained indirectly from experimental determinations of the compounds using isoperibolic calorimetry and thermogravimetry. The values obtained for enthalpy of formation in the gas phase were compared with the computational results by means of the auxiliary density functional theory using deMon2k. The influence of the carbonyl and acetate groups on this type of compounds is analyzed energetically and structurally. The results obtained were compared and discussed with the data found in the literature.

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A new and mild synthetic approach for the synthesis of 6-unsubstituted phenanthridine and phenanthridine-like compounds under metal-free conditions at room temperature has been developed. The strategy involved a tandem azide rearrangement/intramolecular annulation and oxidation reactions of biarylmethyl azide precursors to obtain the desired products in up to 99% yields with high regioselectivity.

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Enzyme inhibitors cause a decrease in the reaction rate of an enzyme-catalyzed reaction by binding to a specific portion of an enzyme and thus slowing or preventing a reaction from occurring. Application In Synthesis of Methyl 4-bromobenzo[b]thiophene-2-carboxylate, C10H7BrO2S. A document type is Patent, introducing its new discovery., Application In Synthesis of Methyl 4-bromobenzo[b]thiophene-2-carboxylate

Substituted indazole or imidazole derivatives of formula I as in vitro selective and reversible MAO-B inhibitors and for use in the prevention and treatment of meurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disase and dementia

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A variety of methylarenes were successfully converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with NBS or DBDMH in the presence of a catalytic amount of AIBN or BPO, followed by the reaction with molecular iodine in aq NH3 in a one-pot procedure. The present reaction is a useful and practical transition-metal-free method for the preparation of aromatic nitriles from methylarenes.

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The hydrogenation of imines to amines in the presence of catalytic amounts of zinc triflate has been demonstrated for the first time. In addition, an efficient procedure for the reductive hydroamination of alkynes to amines is presented using zinc triflate as a catalyst precursor. In both protocols a variety of different functional groups are tolerated, and the reactions proceed smoothly in high yields.

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A genus of proteolysis-targeting chimeras (PROTACs)-type compounds/antiestrogens has now been found that act as selective estrogen receptor degraders (SERDs) and estrogen receptor antagonists by degrading and antagonizing ERa in breast cancer cells. The compounds are of the following genus: The compounds described herein exhibit anti-proliferative effects, and are potentially useful, alone or in combination with other therapies, for the treatment of breast cancer. In general, these compounds combine a tight binding ERa targeting ligand tethered to a recognition motif or degron. Once bound, the degron recruits destructive cellular components and the targeted receptor (i.e., ERa) is degraded (i.e., destroyed) or antagonized.

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This invention is directed to an (aminoiminomethyl or aminomethyl) benzoheteroaryl compound of formula I which is useful for inhibiting the activity of Factor Xa by combining said compound with a composition containing Factor Xa. The present invention is also directed to compositions containing compounds of the formula I, methods for their preparation, their use, such as in inhibiting the formation of thrombin or for treating a patient suffering from, or subject to, a disease state associated with a physiologically detrimental excess amount of thrombin.

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A facile oxidation for the clean conversion of benzo[b]thiophenes to their corresponding sulfones is described employing an aqueous solution of H 2O2 and P2O5; the solution can be prepared and stored on a multi-gram scale with a shelf-life of up to two weeks.

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A copper-catalyzed borylation/benzylic cyanation of vinylarenes whose regioselectivity is seemly common but scarcely achieved is reported. This unprecedented regioselectivity is realized through a structure-distinctive cyanating reagent, dimethylmalononitrile. This reaction can be applied to both ?-extended and simple vinylarenes with various diboron reagents, and it exhibits good functional group compatibility. With the ample transformations of cyano and boronate groups, this reaction provides expedient access to complex organic structures.

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