Bhattarai, Deepak’s team published research in Current Computer-Aided Drug Design in 2014-12-31 | CAS: 19156-54-8

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.

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’s team published research in Journal of Biomolecular Screening in 2016-02-29 | CAS: 40180-04-9

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.

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’s team published research in Toxicology in Vitro in 2010-10-31 | CAS: 40180-04-9

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.

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’s team published research in Chemical Research in Toxicology in 2012-10-15 | CAS: 40180-04-9

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.

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’s team published research in Current Drug Discovery Technologies in 2006-03-31 | CAS: 40180-04-9

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.

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

 

Kakutani, Nobuyuki’s team published research in Journal of Toxicological Sciences in 2019 | CAS: 40180-04-9

Journal of Toxicological Sciences 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, Application In Synthesis of 40180-04-9.

Kakutani, Nobuyuki published the artcileNovel risk assessment of reactive metabolites from discovery to clinical stage, Application In Synthesis of 40180-04-9, the main research area is quetiapine rimonabant ritonavir hepatoprotectant drug discovery liver injury; Body burden; Cyanide; Cysteine; Hepatotoxicity; Reactive metabolites; Trapping assay.

This study was aimed to predict drug-induced liver injury caused by reactive metabolites. Reactive metabolites covalently bind to proteins and could result in severe outcomes in patients. However, the relation between the extent of covalent binding and clin. hepatotoxicity is still unclear. From a perspective of body burden (human in vivo exposure to reactive metabolites), we developed a risk assessment method in which reactive metabolite burden (RM burden), an index that could reflect the body burden associated with reactive metabolite exposure, is calculated using the extent of covalent binding, clin. dose, and human in vivo clearance. The relationship between RM burden and hepatotoxicity in humans was then investigated. The results indicated that this RM burden assessment exhibited good predictability for sensitivity and specificity, and drugs with over 10 mg/day RM burden have high-risk for hepatotoxicity. Furthermore, a quant. trapping assay using radiolabeled trapping agents ([35S]cysteine and [14C]KCN) was also developed, to detect reactive metabolite formation in the early drug discovery stage. RM burden calculated using this assay showed as good predictability as RM burden calculated using conventional time- and cost-consuming covalent binding assays. These results indicated that the combination of RM burden and our trapping assay would be a good risk assessment method for reactive metabolites from the drug discovery stage.

Journal of Toxicological Sciences 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, Application In Synthesis of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

Rana, Payal’s team published research in Bioorganic & Medicinal Chemistry Letters in 2016-08-15 | CAS: 40180-04-9

Bioorganic & Medicinal Chemistry Letters 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, Category: benzothiophene.

Rana, Payal published the artcileDevelopment of a cell viability assay to assess drug metabolite structure-toxicity relationships, Category: benzothiophene, the main research area is drug metabolite toxicity assay cytochrome P 450 structure toxicity; Cytochrome P450; Drug-induced toxicity; Metabolic activation; Reactive metabolite; Structural alerts.

Many adverse drug reactions are caused by the cytochrome P 450 (CYP)-dependent activation of drugs into reactive metabolites. To reduce attrition due to metabolism-induced toxicity and to improve the safety of drug candidates, the authors developed a simple cell viability assay by combining a bioactivation system (human CYP3A4, CYP2D6 and CYP2C9) with Hep3B cells. The authors screened a series of drugs to explore structural motifs that may be responsible for CYP 450-dependent activation caused by reactive metabolite formation, which highlighted specific liabilities regarding certain phenols and anilines.

Bioorganic & Medicinal Chemistry Letters 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, Category: benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

Orr, Suvi T. M.’s team published research in Journal of Medicinal Chemistry in 2012-06-14 | CAS: 40180-04-9

Journal of Medicinal Chemistry 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, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Orr, Suvi T. M. published the artcileMechanism-Based Inactivation (MBI) of Cytochrome P450 Enzymes: Structure-Activity Relationships and Discovery Strategies To Mitigate Drug-Drug Interaction Risks, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is cytochrome P450 enzyme inhibition drug interaction metabolism SAR.

The importance of mitigating drug-drug interaction (DDI) risks, which arise from inhibition of major human cytochrome P 450 enzymes is a well-established component of the lead optimization process in drug discovery. More recently, there has been much interest in clin. DDIs potentially arising via time- and concentration-dependent cytochrome P 450 inhibition, a phenomenon consistent with mechanism-based inactivation. Inactivated P 450 is catalytically incompetent and must be replenished by newly synthesized protein. Consequently, time-dependent inhibition of P450s presents a greater safety concern compared to reversible inhibition because of the increased propensity for pharmacokinetic interactions upon multiple dosing and the sustained duration of these interactions after discontinuation of the mechanism-based inactivator. Mechanism-based or time-dependent P 450 inhibitors pose an addnl. risk of idiosyncratic drug toxicity since the mechanism of time-dependency often involves the formation of reactive metabolites, which can react with proteins other than the P 450 isoenzyme responsible for catalysis. in vitro time-dependent inhibition (TDI) of P 450 enzymes is now routinely assessed as part of lead optimization efforts in preclin. drug discovery. However, identification of an in vitro TDI liability can raise several questions such as: What is the mechanism of TDI. Does it involve the formation of reactive metabolites. Is there a 1:1 correlation between P 450 TDI and RM formation (as measured from reactive metabolite trapping studies). What is the likelihood that a P 450 time-dependent inhibitor will also cause toxicity. What are the DDI risk mitigation options when dealing with P 450 inactivators in drug discovery – compound progression or termination. Several drugs exhibit in vitro TDI of P 450 enzymes, but only a fraction thereof causes clin. DDIs. Hence, when do we initiate labor-intensive medicinal chem. efforts to design compounds devoid of P 450 TDI liability. What are the best methods to precisely predict the likelihood of occurrence of clin. DDIs with drug candidates that inactivate P 450 enzymes. What are (if any) the qualifying considerations for clin. progression of a P 450 time-dependent inactivator with projected clin. DDI risks. In an effort to address these questions and hopefully provide answers to some of them, we embarked on the present venture wherein we highlight the current state-of-the-art knowledge in this field with a special emphasis on (a) available biochem. and mechanistic approaches in drug discovery to examine TDI of P 450 isoenzymes with new chem. entities, (b) structure-activity relationship studies with marketed drugs associated with DDIs via P 450 inactivation, (c) case studies of medicinal chem. tactics to abrogate P 450 inactivation liability, (d) strategies for progression of P 450 TDI-pos. drug candidates, and (e) the utility of in silico methodol., including the use of physiol.-based pharmacokinetic simulators, in drug discovery to predict the magnitude of clin. DDIs risks anticipated with new clin. candidates.

Journal of Medicinal Chemistry 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, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

Dayan, J.’s team published research in Mutation Research, Genetic Toxicology Testing in 1987-02-28 | CAS: 40180-04-9

Mutation Research, Genetic Toxicology Testing published new progress about DNA SOS repair. 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.

Dayan, J. published the artcileApplication of the SOS chromotest to 10 pharmaceutical agents, Quality Control of 40180-04-9, the main research area is drug mutagenesis SOS chromotest assay.

The SOS function-inducing activity of 10 compounds belonging to different chem. classes was studied in Escherichia coli PQ37. The choice of these chems. was based on previously reported mutagenesis studies. This study indicated that 6 compounds which did not induce a pos. response in the Ames test and other mutagenesis tests were also neg. in the SOS chromotest. The other compounds studied had a pos. response in the SOS-inducing function in addition to the pos. results from the Ames test. In order to establish a correlation between these 2 tests a study requiring a larger selection of chem. agents is needed.

Mutation Research, Genetic Toxicology Testing published new progress about DNA SOS repair. 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

 

Davanagere, Haleshappa’s team published research in Journal of Molecular Structure in 2020-11-15 | CAS: 1468-83-3

Journal of Molecular Structure published new progress about Crystal growth. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Quality Control of 1468-83-3.

Davanagere, Haleshappa published the artcileInvestigation of structural, physical, linear, and nonlinear optical properties of two novel thiophene centred D-π-A type push-pull organic derivatives for nonlinear optical applications, Quality Control of 1468-83-3, the main research area is phys linear nonlinear optical thiophene centered organic derivative.

The aim of the present study is to investigate the different key parameters of two novel thiophene based D-π-A type push-pull organic chalcone derivatives; 3-(4-nitrophenyl)- 3-hydroxy-1-(thiophen-2-yl) propan-1-one (2ATN) and 3-(4-nitrophenyl) -3-hydroxy -1-(thiophen-3-yl) propan-1-one (3ATN) through various exptl. techniques. The 2ATN and 3ATN single crystal are grown at ambient temperature by the slow evaporation solution growth technique. The single crystal X-ray diffraction anal. confirmed that both the title compounds 3ATN and 2ATN are crystallized in the triclinic crystal system under centrosym. structure with space group P-1. The 2ATN and 3ATN crystals are thermally stable up to 147.68°C and 197.4°C resp. The linear optical properties of grown crystals are characterized by photoluminescence and UV-visible spectroscopic technique. The Vicker’s microhardness test confirms the crystal’s hardness and the Vicker’s hardness number 19 kg/mm2 and 13 kg/mm2 of 2ATN and 3ATN resp., which are indicates the phys. stability of the crystals. The third-order nonlinear optical parameters are determined using Z-Scan technique under continuous wave laser source at 532 nm wavelength. Using the Kurtz-Perry method SHG efficiency was tested for both the crystals and the 3ATN crystal shows about 0.61 times the efficiency of urea crystal. The nitro substituted effects are described in the enhancement of NLO activity using structure-property relationship. The reported crystals can therefore be used for non-linear optical applications due to its excellent optical properties.

Journal of Molecular Structure published new progress about Crystal growth. 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