Archives for Chemistry Experiments of Methyl benzo[b]thiophene-2-carboxylate

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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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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Design, synthesis and evaluation of benzoheterocycle analogues as potent antifungal agents targeting CYP51

To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compound 1, a series of benzoheterocycle analogues were designed, synthesized and evaluated for their in vitro antifungal activity. The most promising compounds 13s and 14a exhibited excellent antifungal activity against C. albicans, C. neoformans, A. fumigatus and fluconazole-resistant C. albicans strains, that was superior or comparable to those of the reference drugs fluconazole and voriconazole. GC?MS analyses suggested that the novel compound 13s might have a similar mechanism to fluconazole by inhibiting fungal lanosterol 14alpha-demethylase (CYP51). Furthermore, compounds 13s and 14a exhibited low inhibition profiles for various human cytochrome P450 isoforms as well as excellent blood plasma stability.

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Benzothiophene – Wikipedia,
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4-Substituted (benzo[b]thiophene-2-carbonyl)guanidines as novel Na +/H+ exchanger isoform-1 (NHE-1) inhibitors

A series of 4-substituted (benzo[b]thiophene-2-carbonyl)guanidines was synthesized and evaluated for the NHE-1 inhibitory activity and cardioprotective efficacy both in vitro and in vivo. Several analogs exhibited a strong inhibition on NHE-1, and which was generally well correlated with their cardioprotective efficacy. Especially the 4-nitro 20 and cyano 50 compounds excellently improved the cardiac function and reduced infarct size against ischemia/reperfusion injury.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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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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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Synthesis of re1tricarbonyl complexes with various sulfur-and oxygen-donating ligands: Crystal structures of two re1dinuclear structures bridged by S atoms

The synthesis and characterization of two dinuclear complexes, namely fac-hexacarbonyl-1kappa3C,2kappa3C-(pyridine-1kappaN)[mu-2,2?-sulfanediyldi(ethanethiolato)-1kappa2S1,S3:2kappa3S1,S2,S3]dirhenium(I), [Re2(C4H8S3)(C5H5N)(CO)6], (1), and tetraethylammonium fac-tris(mu-2-methoxybenzenethiolato-kappa2S:S)bis[tricarbonylrhenium(I)], (C8H20N)[Re2(C7H7OS)3(CO)6], (2), together with two mononuclear complexes, namely (2,2?-bithiophene-5-carboxylic acid-kappa2S,S?)bromidotricarbonylrhenium(I), (3), and bromidotricarbonyl(methyl benzo[b]thiophene-2-carboxylate-kappa2O,S)rhenium(I), (4), are reported. Crystals of (1) and (2) were characterized by X-ray diffraction. The crystal structure of (1) revealed two Re-S-Re bridges. The thioether S atom only bonds to one of the ReI metal centres, while the geometry of the second ReI metal centre is completed by a pyridine ligand. The structure of (2) is characterized by three S-atom bridges and an Re.Re nonbonding distance of 3.4879?(5)?A, which is shorter than the distance found for (1) [3.7996?(6)/3.7963?(6)?A], but still clearly a nonbonding distance. Complex (1) is stabilized by six intermolecular hydrogen-bond interactions and an O.O interaction, while (2) is stabilized by two intermolecular hydrogen-bond interactions and two O.pi interactions.

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Synthesis and Antitubercular Activity of New Benzo[b]thiophenes

In vitro and ex vivo efficacies of four series of benzo[b]thiophene-2-carboxylic acid derivatives were studied against Mycobacterium tuberculosis H37Ra (MTB). Benzo[b]thiophenes were also tested in vitro against multidrug resistant Mycobacterium tuberculosis H37Ra (MDR-MTB), and 7b was found to be highly active against A- and D-MDR-MTB/MTB (MIC ranges 2.73-22.86 mug/mL). The activity of all benzo[b]thiophenes against M. bovis BCG (BCG) was also assessed grown under aerobic and under conditions of oxygen depletion. Compounds 8c and 8g showed significant activity with MICs of 0.60 and 0.61 mug/mL against dormant BCG. The low cytotoxicity and high selectivity index data against human cancer cell lines, HeLa, Panc-1, and THP-1 indicate the potential importance of the development of benzo[b]thiophene-based 1,3-diketones and flavones as lead candidates to treat mycobacterial infections. Molecular docking studies into the active site of DprE1 (Decaprenylphosphoryl-beta-d-ribose-2?-epimerase) enzyme revealed a similar binding mode to native ligand in the crystal structure thereby helping to understand the ligand-protein interactions and establish a structural basis for inhibition of MTB. In summary, its good activity in in vitro and ex vivo model, as well as its activity against multidrug-resistant M. tuberculosis H37Ra in a potentially latent state, makes 7b an attractive drug candidate for the therapy of tuberculosis.

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Design, Synthesis, and Pharmacological Evaluation of First-in-Class Multitarget N-Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kalpha Inhibitors

Targeting histone deacetylases (HDACs) and phosphatidylinositol 3-kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N-acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kalpha dual inhibitors. The surprising selectivity for PI3Kalpha may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kalpha show potential for the treatment of cancer.

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Determination of partition coefficient of benzo[b]thiophenes by reversed-phase high-performance liquid chromatography

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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Direct Carboxylation of Electron-Rich Heteroarenes Promoted by LiO-tBu with CsF and [18]Crown-6

We herein demonstrate that the combination of LiO-tBu, CsF, and [18]crown-6 efficiently promotes the direct C?H carboxylation of electron-rich heteroarenes (benzothiophene, thiophene, benzofuran, and furan derivatives). A variety of functional groups, including methyl, methoxy, halo, cyano, amide, and keto moieties, are compatible with this system. The reaction proceeds via the formation of a tert-butyl carbonate species.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Investigation on the one-step preparation of 2-substituted benzo[B]thiophenes

A convenient and efficient synthesis of 2-substituted benzo[b]thiophenes is described. This one-step reaction of alkylthiobenzaldehyde and activated electrophiles proceeded smoothly in toluene at 120 C with magnesium oxide as a catalyst. The target 2-substituted benzo[b]thiophenes are obtained in moderate yields and the side reaction is inhibited via azeotropic distillation. According to the experiments, a plausible mechanism is presented.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem