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Non-imidazole histamine H3 ligands. Part VI. Synthesis and preliminary pharmacological investigation of thiazole-type histamine H3-receptor antagonists with lacking a nitrogen nucleus in the side chain

Background: Antagonists to the H3 receptor are considered to be potential drugs for the treatment of Alzheimer’s disease, attention deficit-hyperactive disorder, memory and learning deficits, and epilepsy. The initial development of potent H3 receptor antagonists focused on extensive modification of the natural ligand histamine. However, it has appeared that imidazole-containing ligands are associated with inhibition of cytochrome P450 enzymes, caused by imidazole nitrogen complexation to heme iron in the active site of the enzyme. For these reasons, the development of potent non-imidazole H3 receptor antagonists was eagerly awaited. Objective: Previously, we reported the synthesis and pharmacological in vitro characterization of series of potent histamine H3-receptor non-imidazole antagonists belonging to the class of substituted 2-thiazol-4-n-propylpiperazines. A lead compound 1 of this family was a derivative carrying the ethylaminomethylpropyl chain. Methods: With the aim of increasing lipophilicity, that will help the ligands to cross the blood-brain barrier, we synthesized a series of new 2-thiazol-4-n-propylpiperazines where the ethylaminomethylpropyl moiety was replaced by a p-substituted-, an unsubstituted benzene ring, and omega-phenylalkyl substituent at positions 4 and 5 of thiazole ring, respectively. All compounds were tested for H3 antagonistic effects in vitro using the electrically contracting guinea pig jejunum. Results: The most active compounds of presented series 3d, 3e, and 3j showed lower affinity than the lead compound 1 and additionally, derivatives 3d and 3j possessed weak, competitive H1-antagonistic activity. This is in contrast to the lead compound 1 that has no affinity at H1 receptor. Conclusion: We can conclude that a side chain in the 2-thiazol-4-n-propylpiperazine scaffold should contain a basic center and should be present at a favorable position 5 of thiazole ring.

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Mechanism of SmI2/amine/H2O-promoted chemoselective reductions of carboxylic acid derivatives (esters, acids, and amides) to alcohols

Samarium(II) iodide-water-amine reagents have emerged as some of the most powerful reagents (E = -2.8 V) for the reduction of unactivated carboxylic acid derivatives to primary alcohols under single electron transfer conditions, a transformation that had been considered to lie outside the scope of the classic SmI2 reductant for more than 30 years. In this article, we present a detailed mechanistic investigation of the reduction of unactivated esters, carboxylic acids, and amides using SmI2-water-amine reagents, in which we compare the reactivity of three functional groups. The mechanism has been studied using the following: (i) kinetic, (ii) reactivity, (iii) radical clock, and (iv) isotopic labeling experiments. The kinetic data indicate that for the three functional groups all reaction components (SmI2, amine, water) are involved in the rate equation and that the rate of electron transfer is facilitated by base assisted deprotonation of water. Notably, the mechanistic details presented herein indicate that complexation between SmI2, water, and amines can result in a new class of structurally diverse, thermodynamically powerful reductants for efficient electron transfer to a variety of carboxylic acid derivatives. These observations will have important implications for the design and optimization of new processes involving Sm(II)-reduction of ketyl radicals. (Chemical Equation Presented).

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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hemistry is a science major with cience and engineering. The main research directions are chemical synthesis, preparation and modification of special coatings, and research on the structure and performance of functional materials , Recommanded Product: 214894-89-0. Introducing a new discovery about 214894-89-0, Name is 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine

From ketones to esters by a Cu-catalyzed highly selective C(CO)-C(alkyl) bond cleavage: Aerobic oxidation and oxygenation with air

The Cu-catalyzed aerobic oxidative esterification of simple ketones via C-C bond cleavage has been developed. Varieties of common ketones, even inactive aryl long-chain alkyl ketones, are selectively converted into esters. The reaction tolerates a wide range of alcohols, including primary and secondary alcohols, chiral alcohols with retention of the configuration, electron-deficient phenols, as well as various natural alcohols. The usage of inexpensive copper catalyst, broad substrate scope, and neutral and open air conditions make this protocol very practical. 18O labeling experiments reveal that oxygenation occurs during this transformation. Preliminary mechanism studies indicate that two novel pathways are mainly involved in this process. (Chemical Equation Presented)

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Processes for the preparation of (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol”

The present invention provides various processes for the preparation of (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. These processes may be characterized by the following scheme:

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Total synthesis and evaluation of [18F]MHMZ

Radiochemical labeling of MDL 105725 using the secondary labeling precursor 2-[18F]fluoroethyltosylate ([18F]FETos) was carried out in yields of ?90% synthesizing [18F]MHMZ in a specific activity of ?50 MBq/nmol with a starting activity of ?3 GBq. Overall radiochemical yield including [18F]FETos synthon synthesis, [18F]fluoroalkylation and preparing the injectable [18F]MHMZ solution was 42% within a synthesis time of ?100 min. The novel compound showed excellent specific binding to the 5-HT2A receptor (Ki = 9.0 nM) in vitro and promising in vivo characteristics.

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

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(E)-3-[6-[[(2,6-dichlorophenyl)thio]methyl]-3-(2-phenylethoxy)-2- pyridinyl]-2-propenoic acid: A high-affinity leukotriene B4 receptor antagonist with oral antiinflammatory activity

An extensive structure-activity study based around the high-affinity leukotriene B4 (LTB4) receptor antagonist SB 201146 (1) led to the identification of (E)-3-[6-[[(2,6-dichlorophenyl)thio]methyl]-3-(2- phenylethoxy)-2-pyridinyl]-2-propenoic acid (3). This compound displays high affinity for the human neutrophil LTB4 receptor (K(i) = 0.78 nM), blocks LTB4-induced Ca2+ mobilization with an IC50 of 6.6 ¡À 1.5 nM, and demonstrates potent oral and topical antiinflammatory activity in a murine model of dermal inflammation.

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

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ARYL, ARYLOXY, AND ALKYLOXY SUBSTITUTED 1H-INDOL-3-YL GLYOXYLIC ACID DERIVATIVES AS INHIBITORS OF PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1)

Compounds of formula (I) are provided: wherein R1, R2 and R3, are as defined herein, as well ad pharmaceutical composition and methods using the compounds as inhibitors of plasminogen activator inhibitor (PAI-1) and as therapeutic composition for treating conditions resulting from fibrinolytic disorders, such as deep vein thrombosis, coronary heart disease and pulmonary fibrosis.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Total Asymmetric Synthesis of (+)-Paroxetine and (+)-Femoxetine

Total, asymmetric synthesis of (+)-Paroxetine and (+)-Femoxetine, selective serotonin reuptake inhibitors, used for the treatment of depression, anxiety, and panic disorders is reported. The key step is organocatalytic Michael addition of aldehydes to trans-nitroalkenes realized in bath or continues flow. High efficiency and selectivity in the Michael addition was achieved by application of Wang resin-supported Hayashi?J¡ãrgensen catalyst.

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

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Stereochemical control in microbial reduction. Part 31: Reduction of alkyl 2-oxo-4-arylbutyrates by baker’s yeast under selected reaction conditions

Treatment of baker’s yeast with phenacyl chloride in an aqueous-organic solvent has been proven to be an effective method of inhibiting the enzymes that afford (S)-enantiomers of alpha-hydroxy esters in the reduction of alpha-keto esters. The procedure is effective for the whole-cell system to produce the (R)-product with high chemical yield and high enantiomeric excess.

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

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A new umpolung for direct gamma-regioselective nucleophilic addition of alcohols to gamma-enolizable alpha,beta-unsaturated aldehydes

A direct gamma-regioselective nucleophilic addition of alcohols toward gamma-enolizable alpha,beta-unsaturated aldehydes was developed using a catalytic amount of MeSO3H (30?mol%) and a stoichiometric amount of chloranil (1.0?equiv) as the oxidant. The addition of hexafluoroisopropanol (HFIP) was found to accelerate this cross-dehydrogenative coupling, furnishing diverse alcoholic adducts with high gamma-regio- and E-stereoselectivities.

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