Heterocyclic Building Blocks-Benzothiophene

Abrams, Roman published the artcilePhotocatalytic Difunctionalization of Vinyl Ureas by Radical Addition Polar Truce-Smiles Rearrangement Cascades, COA of Formula: C6H6OS, the main research area is vinyl urea difunctionalization photocatalyst radical polar Truce Smiles rearrangement; SNAr; photochemistry; rearrangement; trifluoromethylation; urea.

The authors report tandem alkyl-arylations and phosphonyl-arylations of vinyl ureas by way of a photocatalytic radical-polar crossover mechanism. Addition of photoredox-generated radicals to the alkene forms a new C-C or C-P bond and generates a product radical adjacent to the urea function. Reductive termination of the photocatalytic cycle generates an anion that undergoes a polar Truce-Smiles rearrangement, forming a C-C bond. The reaction is successful with a range of α-fluorinated alkyl sodium sulfinate salts and diarylphosphine oxides as radical precursors, and the conformationally accelerated Truce-Smiles rearrangement is not restricted by the electronic nature of the migrating aromatic ring. Formally the reaction constitutes an α,β-difuctionalization of a carbon-carbon double bond, and proceeds under mild conditions with visible light and a readily available organic photocatalyst. The products are α,α-diaryl alkylureas typically functionalized with F or P substituents that may be readily converted into α,α-diaryl alkylamines.

Angewandte Chemie, International Edition published new progress about Photocatalysts. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, COA of Formula: C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Meyer, Michael D. published the artcileStructure-Activity Studies for a Novel Series of Tricyclic Substituted Hexahydrobenz[e]isoindole α1A Adrenoceptor Antagonists as Potential Agents for the Symptomatic Treatment of Benign Prostatic Hyperplasia (BPH), Computed Properties of 67189-92-8, the main research area is alpha1A adrenoceptor uroselective hexahydrobenzisoindole synthesis.

In search of a uroselective agent that exhibits a high level of selectivity for the α1A receptor, a novel series of tricyclic hexahydrobenz[e]isoindoles was synthesized. A generic pharmacophoric model was developed requiring the presence of a basic amine core and a fused heterocyclic side chain separated by an alkyl chain. It was shown that the 6-OMe substitution with R, R stereochem. of the ring junction of the benz[e]isoindole and a two-carbon spacer chain were optimal. In contrast to the highly specific requirements for the benz[e]isoindole portion and linker chain, a wide variety of tricyclic fused heterocyclic attachments were tolerated with retention of potency and selectivity. In vitro functional assays for the α1 adrenoceptor subtypes were used to further characterize these compounds, and in vivo models of vascular vs prostatic tone were used to assess uroselectivity.

Journal of Medicinal Chemistry published new progress about Pharmacophores. 67189-92-8 belongs to class benzothiophene, name is Ethyl 3-amino-4-chlorobenzo[b]thiophene-2-carboxylate, and the molecular formula is C11H10ClNO2S, Computed Properties of 67189-92-8.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Usui, Toru published the artcileEvaluation of the potential for drug-induced liver injury based on in vitro covalent binding to human liver proteins, Computed Properties of 40180-04-9, the main research area is drug toxicity liver protein binding.

Prediction of idiosyncratic drug-induced liver injury (DILI) is difficult, and the underlying mechanisms are not fully understood. However, many drugs causing DILI are considered to form reactive metabolites and covalently bind to cellular macromols. in the liver. The objective of this study was to clarify whether the risk of idiosyncratic DILI can be estimated by comparing in vitro covalent binding (CB) levels among 12 pos. compounds (acetaminophen, alpidem, bromfenac, carbamazepine, diclofenac, flutamide, imipramine, nefazodone, tacrine, ticlopidine, tienilic acid, and troglitazone) for DILI and 12 neg. compounds (acetylsalicylic acid, caffeine, dexamethasone, losartan, ibuprofen, paroxetine, pioglitazone, rosiglitazone, sertraline, theophylline, venlafaxine, and zolpidem). After incubation with human liver microsomes in the presence of NADPH, there was a large overlap in the distribution of CB amounts between the pos. and neg. groups. On addition of UDP-glucuronic acid (UDPGA) as a cofactor for glucuronidation, the CB levels of bromfenac and diclofenac were increased. With addition of nucleophilic glutathione (GSH), values for most compounds were decreased. However, separation of the two groups on the basis of CB could not be improved by UDPGA or GSH. Furthermore, CB with human hepatocytes also failed to discriminate pos. from neg. compounds Therefore, the CB amount alone is not sufficient for risk assessment of DILI. In contrast, when the CB amount was multiplied by the maximum daily dose, which may reflect maximum hepatic exposure, the two groups did become discriminated. Taken together, our findings suggest that the combination of CB amount and daily dose can estimate the risk of idiosyncratic DILI.

Drug Metabolism and Disposition published new progress about Hepatotoxicity. 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, Computed Properties of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Saito, Junichiro published the artcileHigh content analysis assay for prediction of human hepatotoxicity in HepaRG and HepG2 cells, Formula: C13H8Cl2O4S, the main research area is drug induced liver injury human hepatocyte cytochrome P450 glutathione; GSH; HCA; HepG2; HepaRG; Hepatotoxicity; ROS.

Drug-induced liver injury (DILI) results in the termination of drug development or withdrawal of a drug from the market. The establishment of a predictive, high-throughput preclin. test system to evaluate potential clin. DILI is therefore required. Here, the authors established a high content anal. (HCA) assay in human hepatocyte cell lines such as the HepaRG with normal expression levels of CYP enzymes and HepG2 with extremely low expression levels of CYP enzymes. Clin. DILI or non-DILI compounds were evaluated for reactive oxygen species (ROS) production, glutathione (GSH) consumption, and mitochondrial membrane potential (MMP) attenuation. A proportion of DILI compounds induced ROS generation, GSH depletion, and MMP dysfunction, which was consistent with reported mechanisms of DILI of these compounds In particular, DILI compounds that deplete GSH via reactive metabolites exhibited a more marked decrease in intracellular GSH or increase in ROS production in HepaRG cells than in HepG2 cells. Comparison of the two cell lines with different levels of CYP expression might help clarify the contribution of metabolism to hepatocyte toxicity. These results suggest that the HCA assay in HepaRG and HepG2 cells might help improve the accuracy of evaluating clin. DILI potential during drug screening.

Toxicology In Vitro published new progress about Hepatotoxicity. 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

Rincon-Villamizar, Edgar published the artcileRules relating hepatotoxicity with structural attributes of drugs, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is hepatotoxicity drug mol structure.

The relationship between mol. structures of drugs and their hepatotoxicity was studied by characterizing their structure in a new way and using formal concept anal., a math. technique to condense knowledge into particular rules, which does not imply linearly assumptions as many conventional statistical techniques. The structural characterization was based on mol. descriptors and mol. frameworks, further decomposed into structural elements, rings, and bridges. The methodol. was applied to drugs in the liver toxicity knowledge base database with the potential to cause drug-induced liver injury. Numbers of atoms and bonds along with the aromatic ratio were suitable descriptors for such drugs. The higher the number of rings and asym. structural elements in their terminal ring systems, the higher is the probability of hepatotoxicity. Rules were found which may help to design drugs which are unlikely to be hepatotoxic.

Toxicological & Environmental Chemistry published new progress about Drugs of abuse. 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

Bhattarai, Deepak published the artcileVirtual Screening and Synthesis of Novel Antitubercular Agents Through Interaction-Based Pharmacophore and Molecular Docking Studies, SDS of cas: 19156-54-8, the main research area is virtual screening antitubercular pharmacophore docking.

Tuberculosis continues to become a major threat and wide spreading disease though out the world. Therefore it is required to identify the new drugs for the treatment of tuberculosis with better activity profile than the prevalent compounds In present study we have screened and modified the antitubercular compounds from com. chem. database using the interaction-based pharmacophore and mol. docking studies. In the first step different pharmacophores of cocrystal structures of enyol acyl carrier reductase (also known as InhA) proteins (2B36 and 3FNG) were generated and employed for screening of ChemDiv database. Four different pharmacophore hypothesis retrieved 3456 hits from approx. 0.67 million compounds In the second filter, these hit mols. were subjected to the mol. docking studies in 2NSD and 3FNG crystal structures. On the basis of high fit values, GScore, structural diversity and visual inspection, one hundred compounds were selected, purchased and subjected to exptl. validation for antitubercular activity against H37Rv Mycobacterium tuberculosis (MTB) strain. Three compounds showed the minimal inhibitory concentration (MIC) value at 16 μg/mL and one compound VH04 showed the value at 1 μg/mL. Then a more active amidoethylamine compound was developed by chem. modifications of the virtual hit VH04 against the MTB strain. We believe that this newly identified scaffold could be useful for the optimization of lead from hit compounds of new antitubercular agents.

Current Computer-Aided Drug Design published new progress about Drug screening. 19156-54-8 belongs to class benzothiophene, name is 4,5,6,7-Tetrahydrobenzo[b]thiophene-3-carboxylic acid, and the molecular formula is C9H10O2S, SDS of cas: 19156-54-8.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Haarhoff, Zuzana published the artcileCoupling laser diode thermal desorption with acoustic sample deposition to improve throughput of mass spectrometry-based screening, SDS of cas: 40180-04-9, the main research area is cytochrome P450 inhibition laser diode thermal desorption acoustic deposition; human cytochrome P450 inhibition high throughput screening mass spectrometry; enzyme assays; label-free technologies; liquid handling; mass spectrometry; multiplex assays and technology.

The move toward label-free screening in drug discovery has increased the demand for mass spectrometry (MS)-based anal. Here we investigated the approach of coupling acoustic sample deposition (ASD) with laser diode thermal desorption (LDTD)-tandem mass spectrometry (MS/MS). We assessed its use in a cytochrome P 450 (CYP) inhibition assay, where a decrease in metabolite formation signifies CYP inhibition. Metabolite levels for 3 CYP isoforms were measured as CYP3A4-1′-OH-midazolam, CYP2D6-dextrorphan, and CYP2C9-4′-OH-diclofenac. After incubation, samples (100 nL) were acoustically deposited onto a stainless steel 384-LazWell plate, then desorbed by an IR laser directly from the plate surface into the gas phase, ionized by atm. pressure chem. ionization (APCI), and analyzed by MS/MS. Using this method, we achieved a sample anal. speed of 2.14 s/well, with bioanal. performance comparable to the current online solid-phase extraction (SPE)-based MS method. An even faster readout speed was achieved when postreaction sample multiplexing was applied, where three reaction samples, one for each CYP, were transferred into the same well of the LazWell plate. In summary, LDTD coupled with acoustic sample deposition and multiplexing significantly decreased anal. time to 0.7 s/sample, making this MS-based approach feasible to support high-throughput screening (HTS) assays.

Journal of Biomolecular Screening published new progress about Drug screening. 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, SDS of cas: 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Gomez-Lechon, Maria Jose published the artcileMechanism-based selection of compounds for the development of innovative in vitro approaches to hepatotoxicity studies in the LIINTOP project, COA of Formula: C13H8Cl2O4S, the main research area is development innovative hepatotoxicity LIINTOP project.

The 6th European Framework Program project LIINTOP was specifically raised to optimize and provide established protocols and exptl. in vitro models for testing intestinal and liver absorption, metabolism and toxicity of mols. of pharmacol. interest. It has been focused on some of the most promising existing liver and intestine in vitro models with the aim of further improving their performance and thus taking them to a pre-normative research stage. Regarding the specific area of the liver, a first basic approach was the optimization of in vitro hepatic models and the development and optimization of in vitro approaches for toxicity screening. New advanced technologies have been proposed and developed in order to determine cellular and mol. targets as endpoints of drug exposure. A key issue in the development and optimization of in vitro hepatotoxicity screening methods was the selection of structurally diverse suitable hepatotoxic reference model compounds to be tested. To this end, a number of solid selection criteria were defined (drugs preferably than chem. agents, well-documented hepatotoxicity in man and well-defined mechanism/s of hepatotoxicity, com. available no volatile compounds with unequivocal CAS number and chem. structure), the strategy followed, including all resources consulted, is described and the selected compounds are extensively illustrated.

Toxicology in Vitro published new progress about Drug screening. 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

Liu, Ruifeng published the artcileLocally Weighted Learning Methods for Predicting Dose-Dependent Toxicity with Application to the Human Maximum Recommended Daily Dose, Category: benzothiophene, the main research area is drug toxicity prediction QSAR learning method.

Toxicol. experiments in animals are carried out to determine the type and severity of any potential toxic effect associated with a new lead compound The collected data are then used to extrapolate the effects on humans and determine initial dose regimens for clin. trials. The underlying assumption is that the severity of the toxic effects in animals is correlated with that in humans. However, there is a general lack of toxic correlations across species. Thus, it is more advantageous to predict the toxicol. effects of a compound on humans directly from the human toxicol. data of related compounds However, many popular quant. structure-activity relationship (QSAR) methods that build a single global model by fitting all training data appear inappropriate for predicting toxicol. effects of structurally diverse compounds because the observed toxicol. effects may originate from very different and mostly unknown mol. mechanisms. In this article, we demonstrate, via application to the human maximum recommended daily dose data that locally weighted learning methods, such as k-nearest neighbors, are well suited for predicting toxicol. effects of structurally diverse compounds We also show that a significant flaw of the k-nearest neighbor method is that it always uses a constant number of nearest neighbors in making prediction for a target compound, irresp. of whether the nearest neighbors are structurally similar enough to the target compound to ensure that they share the same mechanism of action. To remedy this flaw, we proposed and implemented a variable number nearest neighbor method. The advantages of the variable number nearest neighbor method over other QSAR methods include (1) allowing more reliable predictions to be achieved by applying a tighter mol. distance threshold and (2) automatic detection for when a prediction should not be made because the compound is outside the applicable domain.

Chemical Research in Toxicology published new progress about Drug screening. 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, Category: benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Schuster, Daniela published the artcileDevelopment and validation of an in silico P450 profiler based on pharmacophore models, SDS of cas: 40180-04-9, the main research area is Cytochrome P450 inhibitor pharmacophore model enzyme kinetics.

In today’s drug discovery process, the very early consideration of ADME properties is aimed at a reduction of drug candidate drop out rate in later development stages. A part from in vitro testing, in silico methods are evaluated as complementary screening tools for compounds with unfavorable ADME attributes. Especially members of the cytochrome P 450 (P 450) enzyme superfamily. e.g. P 450 1A2, P 450 2C9, P 450 2C19, P 450 2D6, and P 450 3A4, contribute to xenobiotic metabolism, and compound interaction with one of these enzymes is therefore critically evaluated. Pharmacophore models are widely used to identify common features amongst ligands for any target. In this study, both structure-based and ligand-based models for prominent drug-metabolizing members of the P 450 family were generated employing the software packages LigandScout and Catalyst. Essential chem. ligand features for substrate and inhibitor activity for all five P 450 enzymes investigated were determined and analyzed. Finally, a collection of 11 pharmacophores for substrates and inhibitors was evaluated as an in silico P 450 profiling tool that could be used for early ADME estimation of new chem. entities.

Current Drug Discovery Technologies published new progress about Drug discovery. 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, SDS of cas: 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem