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A simple and efficient method has been developed for construction of sulfonylated quinolines via coupling of haloquinolines and sulfonyl chlorides in water. The present methodology provides an attractive approach to various sulfonylated quinolines in moderate to good yields with favorable functional group tolerance, which has the advantages of operation simplicity, readily available starting materials, excellent regioselectivity, scale-up synthesis, and organic solvent-free conditions.

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Transition-metal-catalyzed coupling reactions are useful tools for synthesizing aryl sulfur compounds. However, conventional transition-metal-catalyzed thiolation of aryl bromides and chlorides typically requires the use of strong base under elevated reaction temperature. Herein, we report the first examples of nickel-catalyzed electrochemical thiolation of aryl bromides and chlorides in the absence of an external base at room temperature using undivided electrochemical cells.

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Ziresovir (RO-0529, AK0529) is reported here for the first time as a promising respiratory syncytial virus (RSV) fusion (F) protein inhibitor that currently is in phase 2 clinical trials. This article describes the process of RO-0529 as a potent, selective, and orally bioavailable RSV F protein inhibitor and highlights the in vitro and in vivo anti-RSV activities and pharmacokinetics in animal species. RO-0529 demonstrates single-digit nM EC50 potency against laboratory strains, as well as clinical isolates of RSV in cellular assays, and more than one log viral load reduction in BALB/c mouse model of RSV viral infection. RO-0529 was proven to be a specific RSV F protein inhibitor by identification of drug resistant mutations of D486N, D489V, and D489Y in RSV F protein and the inhibition of RSV F protein-induced cell-cell fusion in cellular assays.

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Facile photoreductive protocols have been developed to remove benzyl O-protective groups from oxyarene N-heterocycles at positions capable for 2-/4-O-pyridine-2-/4-pyridone tautomerism. Blue light irradiation, a [Ru] or [Ir] photocatalyst, and ascorbic acid in a water-acetonitrile solution debenzylates a variety of aryl N-heterocycles cleanly and selectively. Ascorbic acid has two functions in the reaction. On the one hand, it protonates the N-heterocycles that reduces their reduction potentials notably and on the other hand it acts as a sacrificial reductant. Reduction potentials and free energy barriers calculated at the CPCM-B3LYP/6-31+G? level can predict the reactivities of the studied substrates.

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The compounds of the invention are antagonists of MDM2 and/or MDMX, with excellent specificity for MDM2 and/or MDMX over other proteins. Several analogs demonstrate selective binding affinity to MDMX over MDM2. The disclosed compounds can therefore regulate p53 activity and treat a variety of cancers. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

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Substituted 8,9,10,11-tetrahydrodibenzo[b,h][1,6]naphthyridin-6(5H)ones (5) have been synthesized by the condensation of 4-amino-3-formylquinolin-2(1H)ones (4) with cyclohexanone in presence of acetic acid and sulphuric acid. The precusors have been obtained by the animation of 4-chloro-3-formylquinolin-2(1H)ones (3).

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A small-molecule natural product, euodenine A (1), was identified as an agonist of the human TLR4 receptor. Euodenine A was isolated from the leaves of Euodia asteridula (Rutaceae) found in Papua New Guinea and has an unusual U-shaped structure. It was synthesized along with a series of analogues that exhibit potent and selective agonism of the TLR4 receptor. SAR development around the cyclobutane ring resulted in a 10-fold increase in potency. The natural product demonstrated an extracellular site of action, which requires the extracellular domain of TLR4 to stimulate a NF-kappaB reporter response. 1 is a human-selective agonist that is CD14-independent, and it requires both TLR4 and MD-2 for full efficacy. Testing for immunomodulation in PBMC cells shows the induction of the cytokines IL-8, IL-10, TNF-alpha, and IL-12p40 as well as suppression of IL-5 from activated PBMCs, indicating that compounds like 1 could modulate the Th2 immune response without causing lung damage.

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A fungicidal method which comprises applying to the locus of a plant pathogen a fungicidally effective but non-phytotoxic amount of a compound of the formula (1) STR1 wherein: R1 to R4 are independently H, halo, (C1 -C4) alkyl, branched (C3 -C4) alkyl, halo (C1 -C4) alkyl, (C1 -C4) alkoxy, NO2, or HN2, at least two of R1 to R4 being H, or one of R2 to R4 is –NR7 –Y–Ar or O–Y–Ar and the rest of R1 to R4 are H; W is N, or CR5 ; R5 is H, CH3, Cl, O–Y–Ar, or –NR7 –Y–Ar; R6 is H, CH3, Cl, or Br; A is –O–Alk or –X–Y–Ar; Alk is a C2 -C18 saturated or unsaturated hydrocarbon chain, straight chain or branched, optionally substituted with halo, halo (C1 -C4) alkoxy, (C3 -C8) cycloalkyl, hydroxy, or acetyl; X is O, NR7, or CR8 R9, provided that if one of R2 to R5 is NR7 –Y–Ar or O–Y–Ar, then X–Y–Ar is an identical group; R7 is H, (C1 -C4) alkyl, or acetyl; R8 and R9 are independently H, (C1 -C4) alkyl, halo, or OH, or R8 and R9 combine to form a saturated or unsaturated carbocyclic ring comprising three to seven carbon atoms; Y is an alkylene chain 2 to 8 carbon atoms long that optionally includes an O, S, SO, SO2, or NR7 group, and optionally includes a saturated or unsaturated carbocyclic ring comprising three to seven carbon atoms, and optionally is substituted with (C1 -C3) alkyl, (C1 -C4) alkenyl, phenyl, (C3 -C8) cycloalkyl, hydroxy, halo, or acetyl; and Ar is an aryl group.

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Regioselective alkoxydehalogenation reactions using solid alkoxide in toluene have been studied. 2-Alkoxy-4-haloquinolines were obtained from 2,4-dichloroquinolines. With 2,6-dichloropyridine, alpha-regioselectivity occurred to furnish the 2-alkoxy-6-chloropyridine. The reaction failed with 2,4-dichloronitrobenzene indicating that alkoxide surface contact with a basic heterocyclic nitrogen lone pair was essential for success. Comparative studies with the standard alkoxydehalogenation reaction (alcoholic alkoxide solution) have been performed, all compounds have been identified by 1H and 13C NMR.

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4-Aminoquinolone piperidine amides (AQs) were identified as a novel scaffold starting from a whole cell screen, with potent cidality on Mycobacterium tuberculosis (Mtb). Evaluation of the minimum inhibitory concentrations, followed by whole genome sequencing of mutants raised against AQs, identified decaprenylphosphoryl-beta-d-ribose 2?-epimerase (DprE1) as the primary target responsible for the antitubercular activity. Mass spectrometry and enzyme kinetic studies indicated that AQs are noncovalent, reversible inhibitors of DprE1 with slow on rates and long residence times of ?100 min on the enzyme. In general, AQs have excellent leadlike properties and good in vitro secondary pharmacology profile. Although the scaffold started off as a single active compound with moderate potency from the whole cell screen, structure-activity relationship optimization of the scaffold led to compounds with potent DprE1 inhibition (IC50 < 10 nM) along with potent cellular activity (MIC = 60 nM) against Mtb. Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data. Electric Literature of 1055361-35-7, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 1055361-35-7, in my other articles.

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