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A new method for the synthesis of terminal and internal alkynes from the nickel-catalyzed decarboxylative coupling of N-hydroxyphthalimide esters and bromoalkynes is presented. This reductive cross-electrophile coupling is the first to use a C(sp)?X electrophile, and appears to proceed via an alkynylnickel intermediate. The internal alkyne products are obtained in yields of 41?95 % without the need for a photocatalyst, light, or a strong oxidant. The reaction displays a broad scope of carboxylic acid and alkyne coupling partners, and can tolerate an array of functional groups, including carbamate NH, halogen, nitrile, olefin, ketone, and ester moieties. Mechanistic studies suggest that this process does not involve an alkynylmanganese reagent and instead proceeds through nickel-mediated bond formation.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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The heterospirocyclic N-methyl-N-phenyl-5-oxa-1-azaspiro[2.4]hept-1-e n-2-amine (6) and N-(5-oxa-1-azaspiro[2.4]hept-1-en-2-yl)-(S)-proline methyl ester (7) were synthesized from the corresponding heterocyclic thiocarboxamides 12 and 10, respectively, by consecutive treatment with COCl2, 1,4-diazabicyclo[2.2.2]octane, and NaN3 (Schemes 1 and 2). The reaction of these 2H-azirin-3-amines with thiobenzoic and benzoic acid gave the racemic benzamides 13 and 14, and the diastereoisomeric mixtures of the N-benzoyl dipeptides 15 and 16, respectively (Scheme 3). The latter were separated chromatographically. The configurations and solid-state conformations of all six henzamides were determined by X-ray crystallography. With the aim of examining the use of the new synthons in peptide synthesis the reactions of 7 with Z-Leu-Aib-OH to yield a tetrapeptide 17 (Scheme 4), and of 6 with Z-Ala-OH to give a dipeptide 18 (Scheme 5) were performed. The resulting diastereoisomers were separated by means of MPLC or HPLC. NMR Studies of the solvent dependence of the chemical shifts of the NH resonances indicate the presence of an intramolecular H-bond in 17. The dipeptides (S,R)-18 and (S,S)-18 were deprotected at the N-terminus and were converted to the crystalline derivatives (S,R)-19 and (S,S)-19, respectively, by reaction with 4-bromobenzoyl chloride (Scheme 5). Selective hydrolysis of (SR)-18 and (S.S)-18 gave the dipeptide acids (R,S)-20 and (SS)-20, respectively. Coupling of a diastereoisomeric mixture of 20 with H-Phe-O?Bu led to the tripeptides 21 (Scheme 5). X-Ray crystal-structure determinations of (S,R)-19 and (S,S)-19 allowed the determination of the absolute configurations of all diastereoisomers isolated in this series.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

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Leucine rich repeat kinase 2 (LRRK2) has been genetically linked to Parkinson’s disease (PD). The most common mutant, G2019S, increases kinase activity, thus LRRK2 kinase inhibitors are potentially useful in the treatment of PD. We herein disclose the structure, potential ligand-protein binding interactions, and pharmacological profiling of potent and highly selective kinase inhibitors based on a triazolopyridazine chemical scaffold.

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An efficient and operationally simple synthesis of tetrahydrofuran-derived spiro-beta-lactams using the ketene-imine cycloaddition route is described. Also the preparation of spiro-N-sulfonyl-beta-lactam derivatives, which are analogs of monobactams, is reported. As far as we know, this is the first time that an unsymmetrical cyclic ketene is used in a Staudinger-type reaction. The experimental evidence suggests the involvement of a ketene derived from the acyl chloride precursor in the reaction. High-level ab initio calculations have been performed in order to get insight into the electronic effects controlling the stereochemical outcome of the reactions.

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Provided herein are novel sirtuin-modulating compounds represented by Structural Formula (I) and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benfit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin- modulating compound in combination with another therapeutic agent.

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Tetrahydrofuran – Wikipedia,
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An efficient pyridyl-directed Rh(III)-catalyzed o-carborane B(3)-H acyloxylation is reported. The B(3)-H bond is the most electron-deficient vertex on o-carborane whose functionalization is challenging. The combination of Cu(OH)2 and diverse carboxylic acids provides low cost and abundant acyloxyl sources which could lead to moderate to excellent yields.

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Several series of 2,4-dihydro-2,4,5-trisubstituted-3H-1,2,4-triazol-3-ones with acidic sulfonamide replacements of tetrazole at the 2′-position of the biphenyl-4-ylmethyl side chain at N4 were prepared and tested as angiotensin II (AII) antagonists.Preferred substituents on the triazolinone ring were n-butyl at C5 and 2-(trifluoromethyl)phenyl at N2.Subnanomolar IC50 values at the AT1 receptor subtype were observed for a variety of acylsulfonamides, including aroyl, heteroaroyl, and cycloalkylcarbonyl derivatives.Certain other acidic sulfonamides, such as sulfonylcarbamates and disulfimides also displayed high affinity for the AT1 receptor.In addition, AT2 binding for some of these compounds was increased by as much as 1000-fold over the corresponding tetrazole (e.g., AT2 IC50 17 nM for the tert-butyl sulfonylcarbamate 92).When evaluated for inhibition of the AII pressor response, the benchmark benzoylsulfonamide 9 (L-159,913) was efficacious in several species and was superior to losartan (1a) in conscious rhesus monkeys.Several subsequent analogues, including the 2-chlorobenzoyl (18), (3-chlorothiophene-2-yl)carbonyl (51), ((S)-2,2-dimethylcyclopropyl)carbonyl (80), and tert-butoxycarbonyl (92) derivatives, were highly effective in rats, surpassing 9 and losartan in duration of action and/or potency.Compound 18 (L-162,223) displayed very prolonged AII antagonism in the rat model (>24 h at 1 mg/kg iv).At 1 mg/kg po in rats, 18 and 92 (L-162,234) produced 85-87percent peak inhibition of the AII pressor response with duration exceeding 6 h.The identification of triazolinone-based sulfonamide derivatives combining high AT1 affinity, considerably enhanced AT2 potency, and favorable in vivo properties provides insights relevant to the design of dual AT1/AT2 receptor antagonists.

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Tetrahydrofuran – Wikipedia,
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The present invention relates to novel substituted pyrazoloazepin-4-ones with phosphodiesterase inhibitory activity, as well as to their use as therapeutic agents the treatment of inflammatory diseases and conditions.

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The design and synthesis of a series of 11,12-cyclic carbamate derivatives of 6-O-methylerythromycin A that are novel, nonpeptide LHRH antagonists, is described. The macrolide antagonist 1, discovered during a screen of our chemical repository, was compared to a macrocyclic peptide antagonist 2 using molecular modeling, thus providing a model for the design of more potent antagonists. Medicinal chemistry efforts to find a replacement for cladinose at position 3 of the erythronolide core provided a series of oxazolidinone carbamates that were equally as active as the cladinose-containing parent macrolides. The descladinose LHRH antagonist 14 has 1-2 nM affinity for both rat and human LHRH receptors and is a potent inhibitor of LH release (pA 2 = 8.76) in vitro. In vivo, 14 was found to produce a dose-dependent suppression of LH in male castrate rats via both iv and po dosing.

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Tetrahydrofuran – Wikipedia,
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Compounds are disclosed that have a formula represented by the following (I), the compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, traumatic injury, and others.

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Reference:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem