Category: benzothiophene

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

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

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

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

Li, Junhao published the artcileEffects of protein flexibility and active site water molecules on the prediction of sites of metabolism for cytochrome P450 2C19 substrates, COA of Formula: C13H8Cl2O4S, the main research area is mol docking protein structure prediction CYP2C19 water metabolism.

Structure-based prediction of sites of metabolism (SOMs) mediated by cytochrome P450s (CYPs) is of great interest in drug discovery and development. However, protein flexibility and active site water mols. remain a challenge for accurate SOM prediction. CYP2C19 is one of the major drug-metabolizing enzymes and has attracted considerable attention because of its polymorphism and capability of metabolizing ∼7% clin. used drugs. In this study, we systematically evaluated the effects of protein flexibility and active site water mols. on SOM prediction for CYP2C19 substrates. Multiple conformational sampling techniques including GOLD flexible residues sampling, mol. dynamics (MD) and tCONCOORD side-chain sampling were adopted for assessing the influence of protein flexibility on SOM prediction. The prediction accuracy could be significantly improved when protein flexibility was considered using the tCONCOORD sampling method, which indicated that the side-chain conformation was important for accurate prediction. However, the inclusion of the crystallog. or MD-derived water mol.(s) does not necessarily improve the prediction accuracy. Finally, a combination of docking results with SMARTCyp was found to be able to increase the SOM prediction accuracy.

Molecular BioSystems published new progress about Dealkylation. 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, COA of Formula: C13H8Cl2O4S.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

King, Adam M. published the artcileDevelopment of a rapid profiling method for the analysis of polar analytes in urine using HILIC-MS and ion mobility enabled HILIC-MS, Formula: C13H8Cl2O4S, the main research area is urine polar analyte rapid profiling ion mobility HILIC MS; Hydrophilic interaction chromatography; IMS; LC–MS/MS; Metabolic phenotyping.

As large scale metabolic phenotyping is increasingly employed in preclin. studies and in the investigation of human health and disease the current LC-MS/MS profiling methodologies adopted for large sample sets can result in lengthy anal. times, putting strain on available resources. As a result of these pressures rapid methods of untargeted anal. may have value where large numbers of samples require screening. To develop, characterize and evaluate a rapid UHP-HILIC-MS-based method for the anal. of polar metabolites in rat urine and then extend the capabilities of this approach by the addition of IMS to the system. A rapid untargeted HILIC LC-MS/MS profiling method for the anal. of small polar mols. has been developed. The 3.3 min separation used a Waters BEH amide (1 mm ID) anal. column on a Waters Synapt G2-Si Q-Tof enabled with ion mobility spectrometry (IMS). The methodol., was applied to the metabolic profiling of a series of rodent urine samples from vehicle-treated control rats and animals administered tienilic acid. The same separation was subsequently linked to IMS and MS to evaluate the benefits that IMS might provide for metabolome characterization. The rapid HILIC-MS method was successfully applied to rapid anal. of rat urine and found, based on the data generated from the data acquired for the pooled quality control samples analyzed at regular intervals throughout the anal., to be robust. Peak area and retention times for the compounds detected in these samples showed good reproducibility across the batch. When used to profile the urine samples obtained from vehicle-dosed control and those administered tienilic acid the HILIC-MS method detected 3007 mass/retention time features. Anal. of the same samples using HILIC-IMS-MS enabled the detection of 6711 features. Provisional metabolite identification for a number of compounds was performed using the high collision energy MS/MS information compared against the Metlin MS/MS database and, in addition, both calculated and measured CCS values from an exptl. derived CCS database. A rapid metabolic profiling method for the anal. of polar metabolites has been developed. The method has the advantages of speed and both reducing sample and solvent consumption compared to conventional profiling methods. The addition of IMS added an addnl. dimension for feature detection and the identification of metabolites.

Metabolomics published new progress about Homo sapiens. 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, Formula: C13H8Cl2O4S.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Gleeson, M. Paul published the artcilePlasma Protein Binding Affinity and Its Relationship to Molecular Structure: An In-silico Analysis, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is plasma protein binding QSAR.

In-silico plasma protein binding (PPB) models have been generated on human and rat inhouse datasets, and on a human dataset from the literature. From the results reported herein, it is apparent that models built on datasets relevant to the chemotypes under investigation in lead optimization programs will perform considerably better in this role than those generated on diverse compounds from the literature. The inhouse human and rat partial least-squares regression (PLS) models have cross-validated q2 values of 0.53 and 0.42 on the training sets, resp. On the independent test and validation sets, they display similar predictive ability, with logK prediction errors of ∼0.5 log units. This compares to ∼0.25 log units variability expected for experiment Given the considerable interspecies PPB differences, the prediction of PPB in one species using measurements in the other is no better than a prediction from an in-silico model generated on that species.

Journal of Medicinal Chemistry published new progress about Homo sapiens. 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, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Wu, Guosheng published the artcileCharacterization of Glutathione Conjugates of Duloxetine by Mass Spectrometry and Evaluation of in Silico Approaches to Rationalize the Site of Conjugation for Thiophene Containing Drugs, HPLC of Formula: 40180-04-9, the main research area is glutathione conjugate duloxetine mass spectrometry evaluation site conjugation.

The in vitro bioactivation of the selective serotonin and norepinephrine reuptake inhibitor duloxetine was investigated using liver microsomes and cytosol, expressed glutathione transferase, and recombinant P 450 2D6 and 1A2. In the presence of glutathione, several conjugates were identified and characterized using a combination of direct infusion nanoelectrospray mass spectrometry on an LTQ/Orbitrap and liquid-chromatog. mass spectrometry on a triple quadrupole. Structural characterization of these conjugates revealed that glutathione conjugation occurred on naphthalene rather than on thiophene and likely proceeded via a reactive epoxide intermediate. Experiments with recombinant P450s and the isoform specific inhibitors quinidine and furafylline suggested that both P 450 2D6 and 1A2 were involved in the bioactivation of duloxetine. To explore the utility of in silico approaches to address bioactivation issues, MetaSite and two docking approaches (rigid and induced-fit docking) utilizing publicly available human P 450 crystal structures or a homol. model for P 450 2C19 were used to predict the sites of bioactivation for duloxetine as well as the thiophene containing compounds tienilic acid, suprofen, ticlopidine, methapyrilene, and OSI-930 for which glutathione conjugates on the thiophene moiety have been reported. MetaSite and induced fit docking but not rigid docking correctly predicted that naphthalene rather than thiophene was the preferred site of bioactivation for duloxetine by P 450 2D6. MetaSite predictions were also consistent with literature reports that thiophene was the site of glutathione conjugation for tienilic acid, suprofen, and OSI-930 but not for ticlopidine or methapyrilene. Of the two docking approaches investigated, induced fit docking results were consistent with thiophene as the site of bioactivation for all compounds to which it was applied. In conclusion, our investigation identified the likely bioactivation pathway for duloxetine and demonstrated the utility of in silico approaches MetaSite and induced fit docking to address potential bioactivation liabilities.

Chemical Research in Toxicology published new progress about Homo sapiens. 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, HPLC of Formula: 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Nakayama, Shintaro published the artcileCombination of GSH trapping and time-dependent inhibition assays as a predictive method of drugs generating highly reactive metabolites, Quality Control of 40180-04-9, the main research area is glutathione trapping covalent binding liver microsome reactive metabolite pharmacokinetics.

Covalent binding (CB) of reactive metabolites (RMs) is potentially involved in severe adverse drug reactions. Because the CB assay is of low throughput and costly, a qual. trapping assay using agents such as [35S]GSH is often performed in the early stages of drug discovery. However, trapping methods alone cannot replace the CB assay. We hypothesized that the time-dependent inhibition (TDI) assay might be complementary to the [35S]GSH trapping assay in detecting RMs. We performed CB assays, [35S]GSH trapping assays, and TDI assays for 42 structurally diverse compounds First, we showed that the [35S]GSH trapping assay alone does not correlate with the extent of CB. Four compounds that the [35S]GSH trapping assay failed to detect but that showed high extent of CB were inactivators of the enzyme in the TDI assay. There was a tendency for compounds judged as pos. in the TDI assay to show a high degree of CB irresp. of the result of the [35S]GSH trapping assay. Finally, to combine parameters from the two assays, we introduced intrinsic clearance to describe the formation of RMs (CLint, RMs). The Spearman rank correlation coefficient between the extent of CB and CLint, RMs was 0.77 (p < 0.0001), which was better than that for the formation rates of [35S]GSH adducts. Therefore, we demonstrated that a combination of the [35S]GSH trapping and TDI assays is an effective method for detecting compounds potentially capable of generating highly reactive metabolites in the early stages of drug discovery. Drug Metabolism and Disposition published new progress about Homo sapiens. 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, Quality Control of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Yamaoka, Toshikazu published the artcileCharacterization of a highly sensitive and selective novel trapping reagent, stable isotope labeled glutathione ethyl ester, for the detection of reactive metabolites, HPLC of Formula: 40180-04-9, the main research area is reactive metabolite stable isotope glutathione ethyl ester trapping reagent; Bioactivation; Glutathione trapping assay; Idiosyncratic toxicity; Reactive intermediate; Stable isotope.

Glutathione (GSH) trapping assays are widely used to predict the post-marketing risk for idiosyncratic drug reactions (IDRs) in the pharmaceutical industry. Although several GSH derivatives have been introduced as trapping reagents for reactive intermediates, more sensitive and selective reagents are desired to prevent the generation of erroneous results. In this study, stable isotope labeled GSH Et ester (GSHEE-d5) was designed and its detection capability was evaluated. GSHEE-d5 was synthesized and its detection potential was compared with stable isotope labeled GSH ([13C2,15N]GSH) as a reference trapping reagent. The trapping reagents were added to human liver microsomes as a 1:1 mixture with GSHEE or GSH, resp., and incubated with seven IDR pos. drugs and three IDR neg. drugs. The adducts formed between the reagents and reactive metabolites were analyzed by unit resolution mass spectrometer (MS) using isotope pattern-dependent scan with neutral loss filtering. A single-step reaction of GSH and ethanol-d6 produced GSHEE-d5 with a yield of 85%. The GSHEE-d5 assay detected adducts with all seven IDR pos. drugs, and no adducts were detected with the three IDR neg. drugs. In contrast, the [13C2,15N]GSH assay failed to detect adducts with three of the IDR pos. drugs. In the case of diclofenac, the GSHEE-d5 assay showed a 4-times greater signal intensity than the [13C2,15N]GSH assay. GSHEE-d5 enabled the detection of reactive metabolites with greater sensitivity and selectivity than [13C2,15N]GSH. These results demonstrate that GSHEE-d5 would be a useful trapping reagent for evaluating the risk of IDRs with unit resolution MS.

Journal of Pharmacological and Toxicological Methods published new progress about Homo sapiens. 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, HPLC of Formula: 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem