Category: benzothiophene

Wang, Guang-Zu published the artcilePhotocatalytic decarboxylative alkylations of C(sp3)-H and C(sp2)-H bonds enabled by ammonium iodide in amide solvent, Quality Control of 1468-83-3, the main research area is alkylate glycine heteroarene regioselective; aryl glycine heteroarene hydroxyphthalimide redox ester; ammonium iodide salt catalyst decarboxylative alkylation.

A simple ammonium iodide salt in amide solvent catalyzes regioselective decarboxylative alkylation of C(sp3)-H bonds of N-aryl glycine derivatives, of C(sp2)-H bond of heteroarenes, and cascade radical addition to unsaturated bond followed by intramol. addition to arene, with a broad scope of N-hydroxyphthalimide derived redox active esters under visible light irradiation The reactions are suggested to proceed through photoactivation of a transiently assembled chromophore from electron-deficient phthalimide moiety and iodide anion through an anion-π interaction in solvent cage followed by diffusion to generate solvated free radical species to react with C-H substrates. The simplicity, practicality, and broad substrate scope of this method highlight the synthetic power of photocatalysis through transiently assembled chromophore, and will hopefully inspire further developments of low cost photocatalysis based on various non-covalent interactions, which are prevalent in supramol. chem. and biosystems, for sustainable organic synthesis.

Science China: Chemistry published new progress about Alkylation. 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

Lopez-Garcia, M. Pilar published the artcileThiophene derivatives as new mechanism-based inhibitors of cytochromes P-450: Inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic acid, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is thiophene derivative cytochrome P4502C9 suicide substrate; tienilate metabolite cytochrome P4502C9 suicide substrate; immunoallergic hepatitis tienilate metabolite cytochrome P4502C9.

Oxidation of tienilic acid (TA) by microsomes of yeast expressing two closely related human liver cytochrome P-450s (P 450), P 450 2C9 and 2C10, led to catalysis-dependent loss of activity of these P450s. Under identical conditions, oxidation of a tienilic acid isomer (TAI) failed to give any P 450 inactivation. The loss of P 450 activity during TA oxidation was concomitant with product (5-hydroxytienilic acid, 5-OHTA) formulation, showed pseudo-first-order and saturation kinetics, and was inhibited by an alternative substrate, tolbutamide. Covalent binding of TA metabolites to microsomal proteins occurred in parallel with enzyme inactivation and was partially inhibited by the presence of glutathione in the reaction medium. However, glutathione did not protect P 450 enzyme from inactivation. Thus, TA exhibited all of the characteristics of a mechanism-based inactivator for P 450 2C9 and 2C10 enzymes. The following kinetic parameters were determined in the case of P 450 2C10: t1/2,max = 3.4 min, kinact = 3.6 10-3 s-1, KI = 4.3 μM, kinact/K1 = 813 L mol-1 s-1, and partition ratio = 11.6. Moreover, a specific covalent binding of 0.9 mol of TA metabolite per mol of P 450 2C10 was found to occur before the complete loss of enzyme activity (in incubations performed in the presence of glutathione). A plausible mechanism for P 450 2C10 (2C9) inactivation during TA oxidation is proposed. It involves the intermediate formation of an electrophilic thiophene sulfoxide, which may react at position 5 of its thiophene ring either with H2O to give 5-OHTA or with a nucleophilic group of an amino acid residue of the P 450 active site, which results in its covalent binding to P 450 protein. This alkylation and inactivation of P 450 2C9 (2C10) by TA could be a starting point for the appearance of anti-P 4502C antibodies detected in patients treated with TA and suffering from immunoallergic hepatitis.

Biochemistry published new progress about Alkylation. 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

Chan, Alix I. published the artcileDiscovery of a Covalent Kinase Inhibitor from a DNA-Encoded Small-Molecule Library × Protein Library Selection, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is human kinase MAP2K6 inhibitor DNA encoded small mol library.

We previously reported interaction determination using unpurified proteins (IDUP), a method to selectively amplify DNA sequences encoding ligand:target pairs from a mixture of DNA-linked small mols. and unpurified protein targets in cell lysates. In this study we applied IDUP to libraries of DNA-encoded bioactive compounds and DNA-tagged human kinases to identify ligand:protein binding partners out of 32,096 possible combinations in a single solution-phase library × library experiment The results recapitulated known small mol.:protein interactions and also revealed that ethacrynic acid is a novel ligand and inhibitor of MAP2K6 kinase. Ethacrynic acid inhibits MAP2K6 in part through alkylation of a non-conserved cysteine residue. This work validates the ability of IDUP to discover ligands for proteins of biomedical relevance.

Journal of the American Chemical Society published new progress about Alkylation. 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, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Sangion, Alessandro published the artcilePBT assessment and prioritization of contaminants of emerging concern: Pharmaceuticals, Application In Synthesis of 40180-04-9, the main research area is persistence bioaccumulation toxicity assessment prioritization contaminant emerging concern pharmaceutical; PBT; Pharmaceuticals; Prioritization; QSAR; Screening.

The strong and widespread use of pharmaceuticals, together with incorrect disposal procedures, has recently made these products contaminants of emerging concern (CEC). Unfortunately, little is known about pharmaceuticals’ environmental behavior and ecotoxicity, so that EMEA (European Medicines Agency) released guidelines for the pharmaceuticals’ environmental risk assessment. In particular, there is a severe lack of information about persistence, bioaccumulation and toxicity (PBT) of the majority of the thousands of substances on the market. Computational tools, like QSAR (Quant. Structure Activity Relationship) models, are the only way to screen large sets of chems. in short time, with the aim of ranking, highlighting and prioritizing the most environmentally hazardous for focusing further exptl. studies. In this work we propose a screening method to assess the potential persistence, bioaccumulation and toxicity of more than 1200 pharmaceutical ingredients, based on the application of two different QSAR models. We applied the Insubria-PBT Index, a MLR (Multiple Linear Regression) QSAR model based on four simple mol. descriptors, implemented in QSARINS software, and able to synthesize the PBT potential in a unique cumulative value and the US-EPA PBT Profiler that assesses the PBT behavior evaluating sep. P, B and T. Particular attention was given to the study of Applicability Domain in order to provide reliable predictions. An agreement of 86% was found between the two models and a priority list of 35 pharmaceuticals, highlighted as potential PBTs by consensus, was proposed for further exptl. validation. Moreover, the results of this computational screening are in agreement with preliminary exptl. data in the literature. This study shows how in silico models can be applied in the hazard assessment to perform preliminary screening and prioritization of chems., and how the identification of the structural features, mainly associated with the potential PBT behavior of the prioritized pharmaceuticals, is particularly relevant to perform the rational a priori design of new, environmentally safer, pharmaceuticals.

Environmental Research published new progress about Analgesics. 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, Application In Synthesis of 40180-04-9.

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

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

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

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

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

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