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N-Propynyl analogs of beta-phenylethylidenehydrazines: Synthesis and evaluation of effects on glycine, GABA, and monoamine oxidase

A group of beta-phenylethylidenehydrazines possessing a variety of substituents (Me, OMe, Cl, F, and CF3) at the ortho-, meta-, or para-positions of the phenyl ring, in conjunction with either a N-bis-(2-propynyl) or a N-mono-(2-propynyl) moiety, were synthesized and compared to the novel neuroprotective drug beta-phenylethylidenehydrazine (PEH) with regard to their ability to inhibit the enzymes GABA-transaminase (GABA-T) and monoamine oxidase (MAO)-A and -B in vitro in brain tissue. Two of the analogs synthesized (mono- and bis-N-propynylPEH) were also studied ex vivo in rats to compare their effects to those of PEH with regard to ability to inhibit GABA-T and MAO and to change brain levels of several important amino acids. Unlike PEH, none of the new drugs inhibited GABA-T in vitro at 10 or 100 muM, and all of the drugs (including PEH) were poor inhibitors (at 10 muM) of MAO-A and -B in vitro. The two analogs studied ex vivo inhibited GABA-T to a lesser extent than PEH, unlike PEH that did not elevate brain levels of GABA, and inhibited MAO-A and -B more potently than PEH. Interestingly, unlike PEH, the two analogs caused marked increases in brain levels of glycine; because of the current interest in drugs that increase glycine availability in the brain as potential antipsychotic drugs, these two analogs now warrant further investigation.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Ru-Catalyzed Cross-Dehydrogenative Coupling between Primary Alcohols to Guerbet Alcohol Derivatives: With Relevance for Fragrance Synthesis

A simple method has been developed for the cross dehydrogenative coupling between two different primary alcohols using readily available RuCl2(PPh3)3 as a precatalyst through the borrowing-hydrogen approach. The present methodology is applicable to a large variety of alcohol derivatives including long chain aliphatic alcohols and heteroaryl alcohols. In addition, the methodology was applied in a straightforward protocol to synthesize commercially available fragrances such as Rosaphen and Cyclamenaldehyde in good yields.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Hydroesterification of alkenes with sodium formate and alcohols promoted by cooperative catalysis of Ru3(CO)12 and 2-pyridinemethanol

(Figure Presented) A chelation-assisted hydroesterification reaction of alkenes with sodium formate and alcohols that involves cooperative catalysis by Ru3(CO)12 and 2-pyridinemethanol is described. In this three-component coupling reaction, sodium formate serves as the carbon monoxide source.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Iron-Catalyzed beta-Alkylation of Alcohols

beta-Branched alkylated alcohols have been prepared in good yields using a double-hydrogen autotransfer strategy in the presence of our diaminocyclopentadienone iron tricarbonyl complex Fe1. The alkylation of some 2-arylethanol derivatives was successfully addressed with benzylic alcohols and methanol as alkylating reagents under mild conditions. Deuterium labeling experiments suggested that both alcohols (2-arylethanol and either methanol or benzyl alcohol) served as hydrogen donors in this cascade process.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

New explortion of 2,3-Dihydrobenzo[b][1,4]dioxin-6-amine

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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, 22013-33-8, name is 2,3-Dihydrobenzo[b][1,4]dioxin-6-amine, introducing its new discovery. name: 2,3-Dihydrobenzo[b][1,4]dioxin-6-amine

Discovery of potent, orally available vanilloid receptor-1 antagonists. Structure-activity relationship of N-aryl cinnamides

The vanilloid receptor-1 (TRPV1 or VR1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role in regulating the function of sensory nerves. A growing body of evidence demonstrates the therapeutic potential of TRPV1 modulators, particularly in the management of pain. As a result of our screening efforts, we identified (E)-3-(4-tert- butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide (1), an antagonist that blocks the capsaicin-induced and pH-induced uptake of 45Ca2+ in TRPV1-expressing Chinese hamster ovary cells with IC50 values of 17 ¡À 5 and 150 ¡À 80 nM, respectively. In this report, we describe the synthesis and structure-activity relationship of a series of N-aryl cinnamides, the most potent of which (49a and 49b) exhibit good oral bioavailability in rats (Foral = 39% and 17%, respectively).

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Regio- and Enantioselective Iridium-Catalyzed Amination of Racemic Branched Alkyl-Substituted Allylic Acetates with Primary and Secondary Aromatic and Heteroaromatic Amines

The air- and water-stable pi-allyliridium C,O-benzoate modified by (S)-tol-BINAP, (S)-Ir-II, catalyzes highly regio- and enantioselective Tsuji-Trost-type aminations of racemic branched alkyl-substituted allylic acetates using primary or secondary (hetero)aromatic amines. Specifically, in the presence of (S)-Ir-II (5 mol%) in DME solvent at 60-70 C, alpha-methyl allyl acetate 1a (100 mol%) reacts with primary (hetero)aromatic amines 2a-2l (200 mol%) or secondary (hetero)aromatic amines 3a-3l (200 mol%) to form the branched products of allylic amination 4a-4l and 5a-5l, respectively, as single regioisomers in good to excellent yield with uniformly high levels of enantioselectivity. As illustrated by the conversion of heteroaromatic amine 3m to adducts 6a-6g, excellent levels of regio- and enantioselectivity are retained across diverse branched allylic acetates bearing normal alkyl or secondary alkyl substituents. For reactants 3n-3p, which incorporate both primary and secondary aryl amine moieties, regio- and enantioselective amination occurs with complete site-selectivity to furnish adducts 7a-7c. Mechanistic studies involving amination of the enantiomerically enriched, deuterium-labeled acetate 1h corroborate C-N bond formation via outer-sphere addition.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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BENZOTHIAZO AND RELATED HETEROCYCLIC GROUP-CONTAINING CYSTEINE AND SERINE PROTEASE INHIBITORS

The present invention is directed to novel benzothiazo and related heterocyclic group-containing inhibitors of cysteine or serine proteases. Methods for using the same are also described.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Electric Literature of 22013-33-8, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.22013-33-8, Name is 2,3-Dihydrobenzo[b][1,4]dioxin-6-amine, molecular formula is C8H9NO2. In a article£¬once mentioned of 22013-33-8

Identification of 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-N-phenylpropanamides as a novel class of potent DprE1 inhibitors

The identification of a novel series of DprE1 inhibitors based on a 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-N-phenylpropanamide scaffold is described herein. SAR exploration around the HTS hit 1 led to the identification of multiple analogues with potent DprE1 inhibition and good whole-cell antimycobacterial activity.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Design and Synthesis of 1-Heteroaryl-3-(1-benzyl-4-piperidinyl)propan-1-one Derivatives as Potent, Selective Acetylcholinesterase Inhibitors

Herein is described the synthesis and structure-activity relationship of a novel series of aromatic and heteroaromatic 3-(1-benzyl-4-piperidinyl)propan-1-one derivatives that display potent and selective inhibition of the enzyme acetylcholinesterase (AChE). 1-(2-Methyl-6-benzothiazolyl)-3-(N-benzyl-4-piperidinyl)propan-1-one hydrochloride, 6d, is one of the most active compounds within this series exhibiting an IC50 for the inhibition of the AChE enzyme equal to 6.8 nM.Compound 6d has shown a dose-dependent elevation of total acetylcholine (ACh) levels in the mouse forebrain with an oral ED50 = 9.8 mg/kg.In addition, in vivo microdialysis experiments in the rat demonstrate that 6d increases extracellular ACh (100percent over basal) 1-3 h postdose with an oral ED50 = 4.8 mg/kg.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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FUNCTIONALIZED BENZAMIDE DERIVATIVES AS ANTIVIRAL AGENTS AGAINST HBV INFECTION

Pharmaceutical compositions of the invention comprise functionalized benzamide derivatives useful as pregenomic RNA encapsidation inhibitors, and are useful for the treatment of Hepatitis B virus (HBV) infection.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem