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Previous structure-activity relationship studies involving a series of lactone-based muscarinic ligands identified a lead compound containing a diphenylmethylpiperazine moiety (4; IC50 = 340 nM). The purpose of the present work is to investigate 1,3-benzodioxoles, 4,4-diethyl substituted tetrahydrofurans, 5-substituted oxazolidinones and chromones as bioisosteric replacements for the lactone ring in a novel series of muscarinic ligands. The approach provided compounds with improved % inhibition values and identified a non-selective muscarinic ligand with an IC50 value of 280 nM. The structure-activity relationship for this new series will be discussed. Selected compounds were evaluated in preliminary assays for subtype selectivity and were found to be non-selective.

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Described herein are 1,4-substituted piperidine compounds according to Formula (I) that have demonstrated activity as fatty acid synthase inhibitors. Also described herein are pharmaceutical compositions containing the described 1,4-substituted piperidine compounds, and methods of treating diseases mediated by fatty acid synthase, by administering one or more of the compounds or pharmaceutical formulations described herein. Also described herein are methods of synthesizing the compounds described, including the described 1,4-substituted piperidine compounds and synthetic intermediates useful in those syntheses.

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A practical and efficient synthetic route to construct a variety of 3-amidated quinoxalin-2(1H)-ones was developed via transition-metal free direct oxidative amidation of quinoxalin-2(1H)-ones with amidates using Selectfluor reagent as a mild oxidant. This protocol features mild reaction conditions, operational simplicity, broad substrate scope, and good to excellent yields.

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ABSTRACT This invention provides for certain bridged and fused compounds of the formula G-L-A I or a pharmaceutically acceptable salt, ester of solvate thereof wherein: A is: (I) and the other variables are defined herein; the inventive compounds are agonists of the G-protein coupled receptor 40 (GPR40, also known as free fatty acid receptor FFAR). This invention further relates to pharmaceutical compositions containing these compounds, and the use of these compounds to regulate insulin levels in a mammal. The compounds may be used, for example in the prevention and treatment of Type 2 diabetes mellitus and in the prevention and treatment of conditions related to Type 2 diabetes mellitus, such as insulin resistance, obesity and lipid disorders

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The reaction of alpha,beta-unsaturated ketones with benzyl carbamate and 2-oxazolidinone was effectively promoted by a catalytic amount of zirconium (IV) chloride to produce the corresponding beta-amino ketones.

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The bicyclo[4.3.0]nonane (C11-C21) fragment of stawamycin has been prepared by a sequence involving 11 steps (10% overall yield) from methyl (R)-(-)-3-hydroxy-2-methylpropionate. Key steps are a Pd-catalysed Stille coupling reaction between a vinyl iodide and a vinyl stannane followed by an intramolecular Diels-Alder cycloaddition reaction to give the desired adduct as the major isomer in 21% overall yield.

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Copper-catalyzed and highly chemoselective reduction of N-alkynylamides by a boron addition-protonolysis protocol is presented. The reaction proceeds with the addition of boryl-copper complex to N-alkynylamides with high regioselectivity and stereoselectivity, followed by regiocontrolled transmetallation of the alpha-site of the alkenylboronate with MeOCuL to afford N-alkenylamides in good yields. Deuterium labeling experiments indicated that both of the alkenyl hydrogen atoms originate from the additive methanol. The copper-catalyzed semireduction of N-alkynylamides by a boron addition-protonlysis protocol afforded N-alkenylamides in good yields with high stereo- and chemoselectivity. Deuterium labeling experiments indicated that both of the alkenyl hydrogen atoms of the N-alkenylamides originate from the additive methanol. Copyright

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N-Formylsaccharin, an easily accessible crystalline compound, has been employed as an efficient CO source in Pd-catalyzed fluorocarbonylation of aryl halides to afford the corresponding acyl fluorides in high yields. The reactions use a near-stoichiometric amount of the CO source (1.2 equiv) and tolerate diverse functional groups. The acyl fluorides obtained could be readily transformed into various carboxylic acid derivatives such as carboxylic acid, esters, thioesters, and amides in a one-pot procedure.

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Oxidative homocoupling of chiral 3-(arylacetyl)-2-oxazolidones 1 was achieved by treatment with DABCO-TiCl4 or DMAP-TiCl4 and afforded the corresponding dimers stereospecifically. The reaction of (4S)- and (4R)-substituted 1 gave (S,S)- and (R,R)-dimers respectively. The obtained dimers were easily transformed to the corresponding 2,3-diaryl succinic acids. This reaction therefore provides a useful method For the synthesis of optically pure 2,3-diarylsuccinic acids. The oxidative coupling was not inhibited by para substitution of an electron donating group on the aryl group. A para-substituted electron withdrawing group and an ortho-substituent, however, hindered the coupling.

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A practical and mild process to access 2-aminopyridine derivatives using ruthenium-catalyzed [2+2+2] cycloaddition of various 1,6- and 1,7-diynes with cyanamides is described. This straightforward atom-economical catalytic cycloaddition is scalable and showed excellent regioselectivities to approach a wide range of 2-aminopyridines of high synthetic utility. Postfunctionalization reactions of halo-containing adducts, via Pd- and Cu-catalyzed cross-couplings as well as cyanation and amination reactions, delivered substituted 2-aminopyridine derivatives in good to excellent yields.

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