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The octanol-water partition coefficients (log P) for a series of benzo[b]thiophenes were estimated by high performance liquid chromatography on a C18 reversed-phase column, using methanol-water as mobile phase. Measured values for the benzo[b]thiophenes ranged from 2.08 to 4.18. The experimental log P values showed good correlation with those predicted by the Dixon’s method.

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A novel series of 2-benzothiophenealkylpiperazine derivatives 11 (a-d) with potential affinity at 5-HT1A serotonin receptors have been synthesized via solvent-free, microwave-promoted Michael addition of benzo[b]thiophene piperazine derivatives 6(a-c) to substituted benzo[b]thiophen-2-yl propenones 10(b,c).

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A biocatalytic method for the chemoselective aerobic oxidation of aldehydes to carboxylic acids

Herein, we present a study on the oxidation of aldehydes to carboxylic acids using three recombinant aldehyde dehydrogenases (ALDHs). The ALDHs were used in purified form with a nicotinamide oxidase (NOx), which recycles the catalytic NAD+ at the expense of dioxygen (air at atmospheric pressure). The reaction was studied also with lyophilised whole cell as well as resting cell biocatalysts for more convenient practical application. The optimised biocatalytic oxidation runs in phosphate buffer at pH 8.5 and at 40 C. From a set of sixty-one aliphatic, aryl-Aliphatic, benzylic, hetero-Aromatic and bicyclic aldehydes, fifty were converted with elevated yield (up to >99%). The exceptions were a few ortho-substituted benzaldehydes, bicyclic heteroaromatic aldehydes and 2-phenylpropanal. In all cases, the expected carboxylic acid was shown to be the only product (>99% chemoselectivity). Other oxidisable functionalities within the same molecule (e.g. hydroxyl, alkene, and heteroaromatic nitrogen or sulphur atoms) remained untouched. The reaction was scaled for the oxidation of 5-(hydroxymethyl)furfural (2 g), a bio-based starting material, to afford 5-(hydroxymethyl)furoic acid in 61% isolated yield. The new biocatalytic method avoids the use of toxic or unsafe oxidants, strong acids or bases, or undesired solvents. It shows applicability across a wide range of substrates, and retains perfect chemoselectivity. Alternative oxidisable groups were not converted, and other classical side-reactions (e.g. halogenation of unsaturated functionalities, Dakin-Type oxidation) did not occur. In comparison to other established enzymatic methods such as the use of oxidases (where the concomitant oxidation of alcohols and aldehydes is common), ALDHs offer greatly improved selectivity.

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Reference:
Benzothiophene – Wikipedia,
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Morita-Baylis-Hillman route to dimethyl 2,3-Dihydrobenzo[b]oxepine-2,4- dicarboxylates and Methyl 2-(2-carbomethoxybenzo[b]furan-3-yl)propanoates from salicylaldehydes

A new synthetic method for dimethyl 2,3-dihydrobenzo[b]oxepine-2,4- dicarboxylates and methyl 2-(2- carbomethoxybenzo[b]furan-3-yl)propanoates by an intramolecular conjugate displacement reaction or an SN2 reaction of acetates of Morita-Baylis-Hillman adducts of methyl (2-formylphenoxy)acetates has been described.

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Benzothiophene – Wikipedia,
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Ru-Catalyzed Selective C(sp3)?H Monoborylation of Amides and Esters

A ruthenium-catalyzed method has been developed for the C(sp3)?H monoborylation of various unactivated alkyl and aryl amides and challenging esters, with a low-cost and bench-stable boron source, providing boronates with exclusive selectivity, high efficiency, and high turnover number (up to 8900). This novel strategy may offer a versatile and environmentally friendly alternative to current methods for selective C(sp3)?H borylation that employ even more expensive metals, such as iridium and rhodium.

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Benzo[b]thiophene-2-carboxamide derivatives as potent urotensin-II receptor antagonists

Members of a series of benzo[b]thiophene-2-carboxamide derivatives, possessing an N-(1-(3-bromo-4-(piperidin-4-yloxy)benzyl)piperidin-4-yl) group, were synthesized and evaluated as urotensin-II receptor antagonists. The results show that these substances have potent UT binding affinities. Observations made in a systematic SAR investigation of the effects of a variety of substituents (R1and R2) at the 5- and 6-positions in the benzo[b]thiophene-2-carboxamide moiety on UT binding affinities led to identification of the 5-cyano analog 7f as a highly potent UT antagonist with an IC50value of 25 nM. Despite having a good metabolic stability, 7f is a potent inhibitor of CYP isozyme and displays an unsuitable PK profile.

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Benzothiophene – Wikipedia,
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Imidazole-containing fused three-ring compounds and uses thereof (by machine translation)

The invention discloses a formula (I) containing the structure shown as the imidazole fused three-ring compound or its pharmaceutically acceptable salt or a stereoisomer thereof or its prodrug molecule. The compound has adjusting IDO1 active role, such compounds by blocking immune checkpointing IDO1, T cell activation can be enhanced, used for the treatment of IDO1 mediated immune suppression, thus can become effective drug for the treatment of malignant tumor. With the checkpointing the antibody of the protein drug or other anti-cancer drugs share, can enhance the anti-cancer effects. At the same time also has the potential to effectively treat with IDO1 related with the immunosuppressive disease, have high application value. (by machine translation)

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[1]Benzothieno[3,2-b]furans

A new class of organic chemical compounds [1]benzothieno[3,2-b]furans, are made by O-alkylation of 3-hydroxybenzo[b]thiophene-2-carboxylates with alkyl haloacetates, haloacetonitriles or alpha-halomethyl alkyl ketones, followed by cyclization of the intermediate products with alkali metals or alkali metal alkoxides. The compounds are antimicrobials.

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Synthesis and electrochemical reduction of methyl 3-halo-1-benzothiophene- 2-carboxylates

A preparative method of synthesis of the new methyl 3-iodo-1- benzothiophene-2-carboxylate was elaborated. Electrochemical behavior of methyl 3-chloro-, bromo- and iodo-1-benzothiophene-2-carboxylates 1-3, and of their reduction and dimer products 4, 5 in anhydrous dimethylformamide has been investigated at mercury and platinum electrodes using polarography, cyclic voltammetry and voltammetry on a rotating platinum disk electrode. The reduction in divided cells follows the ECE mechanism (electron – chemical step – electron), where the primary radical anion is split into a halide anion and neutral heterocyclic radical, which is immediately reduced by the second electron and protonated. The only reduction product is the methyl 1-benzothiophene-2-carboxylate (5); whereas the EDim mechanism (electron – dimer formation) leading to the dimeric species 4 was not observed under the above conditions. Reduction of 1-3 on platinum causes formation of a blocking film on the electrode. Sonication during electrolysis successfully reactivates the electrode.

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Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model

FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV4-11 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML.

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