Heterocyclic Building Blocks-Benzothiophene

Wu, Qihui published the artcileIn silico identification and mechanism exploration of hepatotoxic ingredients in traditional Chinese medicine, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is hepatotoxic ingredient traditional Chinese medicine; consensus model; hepatotoxicity mechanism; herb induced liver injury; in silico; traditional chinese medicine.

Backgrounds and Aims: Recently, a growing number of hepatotoxicity cases aroused by Traditional Chinese Medicine (TCM) have been reported, causing increasing concern. To date, the reported predictive models for drug induced liver injury show low prediction accuracy and there are still no related reports for hepatotoxicity evaluation of TCM systematically. Addnl., the mechanism of herb induced liver injury (HILI) still remains unknown. The aim of the study was to identify potential hepatotoxic ingredients in TCM and explore the mol. mechanism of TCM against HILI. Materials and Methods: In this study, we developed consensus models for HILI prediction by integrating the best single classifiers. The consensus model with best performance was applied to identify the potential hepatotoxic ingredients from the Traditional Chinese Medicine Systems Pharmacol. database (TCMSP). Systems pharmacol. analyses, including multiple network construction and KEGG pathway enrichment, were performed to further explore the hepatotoxicity mechanism of TCM. Results: 16 single classifiers were built by combining four machine learning methods with four different sets of fingerprints. After systematic evaluation, the best four single classifiers were selected, which achieved a Matthews correlation coefficient (MCC) value of 0.702, 0.691, 0.659, and 0.717, resp. To improve the predictive capacity of single models, consensus prediction method was used to integrate the best four single classifiers. Results showed that the consensus model C-3 (MCC = 0.78) outperformed the four single classifiers and other consensus models. Subsequently, 5,666 potential hepatotoxic compounds were identified by C-3 model. We integrated the top 10 hepatotoxic herbs and discussed the hepatotoxicity mechanism of TCM via systems pharmacol. approach. Finally, Chaihu was selected as the case study for exploring the mol. mechanism of hepatotoxicity. Conclusion: Overall, this study provides a high accurate approach to predict HILI and an in silico perspective into understanding the hepatotoxicity mechanism of TCM, which might facilitate the discovery and development of new drugs.

Frontiers in Pharmacology published new progress about Bupleurum. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Castellanos-Soriano, Jorge published the artcilePhotoredox catalysis powered by triplet fusion upconversion: arylation of heteroarenes, Related Products of benzothiophene, the main research area is furan thiophene arylation photoredox catalysis; Arylations; Furans; Photon upconversion; Photoredox catalysis; Thiophenes; Triplet fusion (triplet–triplet annihilation); Visible light.

In this work, the feasibility of triplet fusion upconversion (TFU, also named triplet-triplet annihilation upconversion) technol. for the functionalization (arylation) of furans and thiophenes has been successfully proven. Activation of aryl halides by TFU leads to generation of aryl radical intermediates; trapping of the latter by the corresponding heteroarenes, which act as nucleophiles, affords the final coupling products. Advantages of this photoredox catalytic method include the use of very mild conditions (visible light, standard conditions), employment of com. available reactants and low-loading metal-free photocatalysts, absence of any sacrificial agent (additive) in the medium and short irradiation times. The involvement of the high energetic delayed fluorescence in the reaction mechanism has been evidenced by quenching studies, whereas the two-photon nature of this photoredox arylation of furans and thiophenes has been manifested by the dependence on the energy source power. Finally, the scaling-up conditions have been gratifyingly afforded by a continuous-flow device.

Photochemical & Photobiological Sciences published new progress about Arylation. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Related Products of benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Whitby, Landon R. published the artcileQuantitative Chemical Proteomic Profiling of the in Vivo Targets of Reactive Drug Metabolites, Synthetic Route of 40180-04-9, the main research area is troglitazone acetaminophen clozapine tienilate hepatotoxicity proteomic profiling drug metabolite.

Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, the authors describe a quant. chem. proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogs of four representative hepatotoxic drugs, the authors demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e.g., lipid/sterol pathways for troglitazone). Site-specific proteomics revealed that acetaminophen reacts with high stoichiometry with several conserved, functional (seleno)cysteine residues throughout the liver proteome. The authors’ findings thus provide an advanced exptl. framework to characterize the proteomic reactivity of drug metabolites in vivo, revealing target profiles that may help to explain mechanisms and identify risk factors for drug-induced liver injury.

ACS Chemical Biology published new progress about Apoptosis. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Synthetic Route of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Huang, Chun published the artcileI2/CuCl2-Copromoted Formal [4 + 1 + 1] Cyclization of Methyl Ketones, 2-Aminobenzonitriles and Ammonium Acetate: Direct Access to 2-Acyl-4-aminoquinazolines, Computed Properties of 1468-83-3, the main research area is aminoquinazolinyl aryl methanone preparation; aryl ethanone aminobenzonitrile ammonium acetate cyclization.

An I2/CuCl2-copromoted diamination of C(sp3)-H bonds for the preparation of 2-acyl-4-aminoquinazolines I [Ar = Ph, 1-naphthyl, 4-MeOC6H4, etc.; R = 8-Me, 6-Cl, 7-MeO, etc.] from Me ketones, 2-aminobenzonitriles, and ammonium acetate was reported. This reaction featured operational simplicity, com. available substrates, mild reaction conditions, and good functional group compatibility. Mechanistic studies indicated that CuCl2 played a pivotal role in this transformation. This study uses a Me group as a novel input to construct 2-acyl-4-aminoquinazoline derivatives for the first time.

Journal of Organic Chemistry published new progress about Amination. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Computed Properties of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Hu, Yongzhi published the artcileElectrochemical oxidative synthesis of 2-benzoylquinazolin-4(3H)-one via C(sp3)-H amination under metal-free conditions, Quality Control of 1468-83-3, the main research area is benzoylquinazolinone green preparation; aminobenzamide ketone electrochem oxidative amination TBAI catalyst.

An electrochem. induced C(sp3)-H amination of 2-aminobenzamides with ketones using TBAI as a catalyst was developed to provide 2-benzoylquinazolin-4(3H)-ones I [R1 = H, 6-F, 7-Me, etc.; R2 = Ph, 2-pyridyl, 3-MeC6H4, etc.] under metal-free conditions. The reaction proceeded using the relatively low-toxicity methanol as the solvent, employed mol. oxygen as the ideal green oxidant in a simple undivided cell and exhibited high atom economy.

Catalysis Science & Technology published new progress about Amination. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Quality Control of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Zhang, Bo published the artcileDiscovery of novel aminophosphonate derivatives containing pyrazole moiety as potential selective COX-2 inhibitors, Quality Control of 1468-83-3, the main research area is aminophosphonate preparation anticancer pyrazole inhibitor amidation human COX MSBAR; Aminophosphonate derivatives; Anti-cancer activity; Apoptosis induction; Cyclooxygenase 2; Mitochondrion-dependent pathway; Pyrazole moiety.

Cyclooxygenase is critical for maintaining physiol. functions, whereas overexpression of COX-2 was closely implicated in various cancers. In this study, a series of novel aminophosphonate derivatives containing pyrazole moiety were synthesized with their anti-cancer activity evaluated. In vitro assays of the target compounds showed that (I) displayed excellent COX-2 inhibitory activity against COX-2 (IC50 = 0.22 ± 0.04μM) and anti-proliferative activity against MCF-7 cell (IC50 = 4.37 ± 0.49μM). The apoptosis induction of compound I was confirmed by flow cytometry and polymerase chain reaction. Further investigation demonstrated that compound I induced apoptosis of MCF-7 cells through a mitochondrion-dependent pathway and involved cell-cycle arrest in G2 phase. Overall, these results provided some new insights into the design of therapeutic drugs for COX-2 inhibitors and indicated the connection between selective COX-2 inhibition and the anti-tumor activity.

Bioorganic Chemistry published new progress about Amidation. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Quality Control of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Cruz-Monteagudo, Maykel published the artcileComputational chemistry approach for the early detection of drug-induced idiosyncratic liver toxicity, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is hepatotoxicity drug computational chem QSAR.

Idiosyncratic drug toxicity (IDT), considered as a toxic host-dependent event, with an apparent lack of dose response relationship, is usually not predictable from early phases of clin. trials, representing a particularly confounding complication in drug development. Albeit a rare event (usually <1/5000), IDT is often life threatening and is one of the major reasons new drugs never reach the market or are withdrawn post marketing. Computational methodologies, like the computer-based approach proposed in the present study, can play an important role in addressing IDT in early drug discovery. We report for the first time a systematic evaluation of classification models to predict idiosyncratic hepatotoxicity based on linear discriminant anal. (LDA), artificial neural networks (ANN), and machine learning algorithms (OneR) in conjunction with a 3D mol. structure representation and feature selection methods. These modeling techniques (LDA, feature selection to prevent over-fitting and multicollinearity, ANN to capture nonlinear relationships in the data, as well as the simple OneR classifier) were found to produce QSTR models with satisfactory internal cross-validation statistics and predictivity on an external subset of chems. More specifically, the models reached values of accuracy/sensitivity/specificity over 84%/78%/90%, resp. in the training series along with predictivity values ranging from ca. 78 to 86% of correctly classified drugs. An LDA-based desirability anal. was carried out in order to select the levels of the predictor variables needed to trigger the more desirable drug, i.e. the drug with lower potential for idiosyncratic hepatotoxicity. Finally, two external test sets were used to evaluate the ability of the models in discriminating toxic from nontoxic structurally and pharmacol. related drugs and the ability of the best model (LDA) in detecting potential idiosyncratic hepatotoxic drugs, resp. The computational approach proposed here can be considered as a useful tool in early IDT prognosis. Journal of Computational Chemistry published new progress about Algorithm. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Cai, Yuxing published the artcileN-Heterocyclic Carbene-Catalyzed 1,4-Alkylacylation of 1,3-Enynes, Product Details of C6H6OS, the main research area is allenone preparation; enyne aldehyde radical precursor alkylacylation heterocyclic carbene catalyst.

The radical relay coupling reaction recently emerged as a powerful synthetic strategy for producing tetrasubstituted allenes R(R1CHR2)C=C=C(R3)C(O)R4 (R = H, Me; R1 = trifluoromethyl, 1,1-difluoro-2-methoxy-2-oxoethyl, 3-cyanopropyl, etc.; R2 = Me, Ph, thiophen-3-yl, pyridin-3-yl, etc.; R3 = hexyl, cyclopropyl, Ph, 4-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)butyl, etc.; R4 = Ph, furan-2-yl, pyridin-3-yl, etc.). However, bond-forming processes involving the allenyl radical intermediate are mostly limited to those promoted by transition metals. In this report, a ketyl radical generated from single-electron oxidation of the Breslow intermediate, which is an excellent coupling partner of allenyl radicals is described. An organocatalytic 1,4-alkylacylation of 1,3-enynes RCH=C(R2)CCR3 occurred smoothly in the presence of an aldehyde R4CHO, a radical precursor, and an N-heterocyclic carbene catalyst. This transformation showed remarkable tolerance to both aromatic and aliphatic aldehydes, enyne substitution, and diversified radical precursors.

Organic Letters published new progress about Acylation. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Product Details of C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Huang, Jingjia published the artcileSynthesis of N-Alkylpyridin-4-ones and Thiazolo[3,2-a]pyridin-5-ones through Pummerer-Type Reactions, Formula: C6H6OS, the main research area is alkylpyridinone thiazolopyridinone preparation Pummerer.

N-Alkylated 4-pyridones were obtained through a one-pot procedure involving either normal or interrupted Pummerer reactions between triflic anhydride-activated sulfoxides and 4-fluoropyridine derivatives, followed by hydrolysis. However, triflic anhydride-activated benzyl 6-fluoro-2-pyridyl sulfoxide could react with alkenes or alkynes to afford thiazolo[3,2-a]pyridin-5-ones, via the pyridinium salt intermediates.

Journal of Organic Chemistry published new progress about Hydrolysis. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Formula: C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

McGinnity, Dermot F. published the artcileEvaluation of time-dependent cytochrome P450 inhibition using cultured human hepatocytes, Synthetic Route of 40180-04-9, the main research area is drug cytochrome P450 inhibition human hepatocyte.

Primary human hepatocytes in culture are commonly used to evaluate cytochrome P 450 induction via an enzyme activity endpoint. However, other processes can confound data interpretation. To this end, the impact of time-dependent P 450 inhibition in this system was evaluated. Using a substrate-cassette approach, P 450 activities were determined after incubation with the prototypic inhibitors tienilic acid (CYP2C9), erythromycin, troleandomycin, and fluoxetine (CYP3A4). Kinetic anal. of enzyme inactivation in hepatocytes was used to describe the effect of these time-dependent inhibitors and derive the inhibition parameters kinact and Kl, which generally were in good agreement with the values derived using recombinant P450s and human liver microsomes (HLMs). Tienilic acid selectively inhibited CYP2C9-dependent diclofenac 4′-hydroxylation activity, and erythromycin, troleandomycin, and fluoxetine inhibited CYP3A4-dependent midazolam 1′-hydroxylation in a time- and concentration-dependent manner. Fluoxetine also inhibited CYP2C19-dependent S-mephenytoin 4′-hydroxylation in a time- and concentration-dependent manner in hepatocytes, HLMs, and recombinant CYP2C19 (Kl 0.4 μM and kinact 0.5 min-1). As expected, the effect of fluoxetine on CYP2D6 in hepatocytes was consistent with potent yet reversible inhibition. A very weak time-dependent CYP2C9 inhibitor (AZ1, a proprietary AstraZeneca compound; Kl 30 μM and kinact 0.02 min-1) effectively abolished CYP2C9 activity over 24 h at low (micromolar) concentrations in primary cultured human hepatocytes. This work demonstrates that caution is warranted in the interpretation of enzyme induction studies with metabolically stable, weak time-dependent inhibitors, which may have dramatic inhibitory effects on P 450 activity in this system. Therefore, in addition to enzyme activity, mRNA and/or protein levels should be measured to fully evaluate the P 450 induction potential of a drug candidate.

Drug Metabolism and Disposition published new progress about Hepatocyte. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Synthetic Route of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem