Heterocyclic Building Blocks-Benzothiophene

Dahlinger, Dominik published the artcileDevelopment and validation of an in vitro, seven-in-one human cytochrome P 450 assay for evaluation of both direct and time-dependent inhibition, Formula: C13H8Cl2O4S, the main research area is cytochrome P450 isoform human assay time dependent inhibition validation; Cytochrome P450; Drug–drug interactions; Methods; N-in-one; Single point inactivation; Time-dependent inhibition.

Direct and time-dependent inhibition (TDI) of cytochrome P 450 (CYP) isoforms raises drug safety concerns and has major implications in drug development. This study describes the development of a liquid chromatog.-tandem mass spectrometry (LC-MS/MS)-based screening tool to simultaneously assess both the direct and the time-dependent inhibitory potential of xenobiotics on the 7 major CYPs using a 2-step approach. The in vitro cocktail of FDA-recognized model substrates was incubated with human liver microsomes (HLM) and consisted of caffeine (CYP1A2), bupropion (CYP2B6), rosiglitazone (CYP2C8), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A4). Direct and time-dependent inhibitory profiles of direct and time-dependent reference inhibitors for each CYP were studied. For validation, the results were compared to those obtained with the traditional single substrate approach. Statistical uncertainty was quantified using the bootstrap method. The direct inhibition assay showed an acceptable fold bias of 1.35 (geometric mean fold absolute deviation, range 1.01-2.61) in the IC50 values for the cocktail assay compared to the single substrate results with no trend for under- or overestn. Using a single point inactivation assay to assess TDI, the authors were able to identify all 7 tested time-dependent reference inhibitors, without any false negatives. The presented design enhanced throughput by assessing the 7 major CYPs simultaneously and allowed for the detection of and discrimination between direct and time-dependent CYP inhibition via IC50 and single point inactivation experiments For the latter, a threshold of 10% TDI was proposed for carrying out more detailed inactivation kinetic experiments

Journal of Pharmacological and Toxicological Methods published new progress about Drug interactions. 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

Parmentier, Yannick published the artcileDirect and quantitative evaluation of the major human CYP contribution (fmCYP) to drug clearance using the in vitro Silensomes model, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is drug metabolism clearance CYP Silensome; Phenotyping; cytochrome; drug–drug interaction; mechanism based inhibitor; metabolism; microsomes.

We have applied the concept of using MBIs to produce CYP-Silensomes to quantify the contribution of the major CYPs to drug metabolism (fmCYP). The target CYPs were extensively and selectivity inhibited by the selected MBIs, while non-target CYPs were inhibited by less than 20% of the homologous control activities. Only CYP2D6-Silensomes exhibited a CYP2B6 inhibition that could be easily and efficiently encountered by subtracting the fmCYP2B6 measured using CYP2B6-Silensomes to adjust the fmCYP2D6.3. To validate the use of a panel of 6 CYP-Silensomes, we showed that the fmCYP values of mono- and multi-CYP metabolized drugs were well predicted, with 70% within ± 15% accuracy. Moreover, the correlation with observed fmCYP values was higher than that for rhCYPs, which were run in parallel using the same drugs (<45% within ±15% accuracy). Moreover, the choice of the RAF substrate in rhCYP predictions was shown to affect the accuracy of the fmCYP measurement. These results support the use of CYP1A2-, CYP2B6-, CYP2C8-, CYP2C9-, CYP2D6 and CYP3A4-Silensomes to accurately predict fmCYP values during the in vitro enzyme phenotyping assays in early, as well as in development, phases of drug development. Xenobiotica published new progress about Drug interactions. 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

Zuniga, Freddi I. published the artcileIdiosyncratic reactions and metabolism of sulfur-containing drugs, Application In Synthesis of 40180-04-9, the main research area is review sulfur containing idiosyncratic drug reaction metabolism toxicity.

Introduction: Idiosyncratic drug reactions (IDRs) that involve the formation of toxic metabolites followed by covalent binding to cellular proteins often go undiscovered until after post-marketing. The goal of this article is to review the current status of IDRs, potential mechanisms and the challenges associated with predicting drug toxicity.Areas covered: The authors review the metabolic pathways of five select classes of sulfur-containing drugs (captopril, troglitazone, tienilic acid, zileuton, methimazole and sudoxicam) suggesting that bioactivation plays a crucial role in the occurrence of IDRs. The reader will gain further awareness that the sulfur atom can propagate as the bioactivation site for the formation of reactive and conceivably toxic metabolites. As such, it is the body’s capacity to detoxify these drug products that may determine whether IDRs occur.Expert opinion: Incomplete understanding of mechanisms culminating in IDR occurrence represents a monumental impediment toward their abrogation. Moreover, current technol. utilized to predict their manifestation (including structure-toxicity relationships) is not infallible and thus, development of novel tools and strategies is indispensible. In an attempt to streamline clin. development and drug approval processes, consortiums have been instated under the US FDA Critical Path Initiative. Collectively, these parameters along with the availability of validated biomarkers and new/updated regulatory guidance could pos. influence the outcome of drug toxicity profiles and direct future drug development.

Expert Opinion on Drug Metabolism & Toxicology published new progress about Drug interactions. 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

O’Reilly, Robert A. published the artcileTicrynafen-racemic warfarin interaction: hepatotoxic or stereoselective?, Product Details of C13H8Cl2O4S, the main research area is ticrynafen warfarin interaction stereoselective.

Normal subjects received large single doses of 1.5 mg/kg racemic warfarin (racemic I) [81-81-2] with and without daily oral doses of 250 mg ticrynafen (II) [40180-04-9] beginning 3 days before I and continuing for the duration of hypoprothrombinemia. II induced augmentations of both prothrombin time and plasma I concentration The interaction was evaluated further with separated I enantiomorphs. II induced augmentation of prothrombin times and I concentrations of S-I  [5543-57-7], but had little effect on R-I  [5543-58-8]. Thus, II probably augments the hypoprothrombinemia of racemic I by reducing metabolic clearance of S-I. The lack of effect of II on R-I suggests that the interaction is stereoselective rather than hepatotoxic.

Clinical Pharmacology & Therapeutics (St. Louis, MO, United States) published new progress about Drug interactions. 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, Product Details of C13H8Cl2O4S.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Yasuo, Kazuya published the artcileStructure-Based CoMFA As a Predictive Model – CYP2C9 Inhibitors As a Test Case, Application In Synthesis of 40180-04-9, the main research area is structure CoMFA CYP2C9 inhibitor.

In this study, we tried to establish a general scheme to create a model that could predict the affinity of small compounds to their target proteins. This scheme consists of a search for ligand-binding sites on a protein, a generation of bound conformations (poses) of ligands in each of the sites by docking, identifications of the correct poses of each ligand by consensus scoring and MM-PBSA anal., and a construction of a CoMFA model with the obtained poses to predict the affinity of the ligands. By using a crystal structure of CYP 2C9 and the twenty known CYP inhibitors as a test case, we obtained a CoMFA model with a good statistics, which suggested that the classification of the binding sites as well as the predicted bound poses of the ligands should be reasonable enough. The scheme described here would give a method to predict the affinity of small compounds with a reasonable accuracy, which is expected to heighten the value of computational chem. in the drug design process.

Journal of Chemical Information and Modeling published new progress about Crystal structure. 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

Weber, Jane E. published the artcileIdentification and characterisation of new inhibitors for the human hematopoietic prostaglandin D2 synthase, SDS of cas: 40180-04-9, the main research area is crystal structure inhibitor human hematopoietic prostaglandin D2 synthase.

Prostaglandin D2 synthesized by the hematopoietic prostaglandin D2 synthase has a pro-inflammatory effect in allergic asthma, regulating many hallmark characteristics of the disease. Here we describe identification of hematopoietic prostaglandin D2 synthase inhibitors including cibacron blue, bromosulfophthalein and ethacrynic acid. Expansion around the drug-like ethacrynic acid identified a novel inhibitor, nocodazole, and a fragment representing its aromatic core. Nocodazole binding was further characterized by docking calculations in combination with conformational strain anal. The benzyl thiophene core was predicted to be buried in the active site, binding in the putative prostaglandin binding site, and a likely hydrogen bond donor site identified. X-ray crystallog. studies supported the predicted binding mode.

European Journal of Medicinal Chemistry published new progress about Crystal structure. 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

Preusch, Peter C. published the artcileMechanism of ticrynafen potentiation of coumarin anticoagulant action, HPLC of Formula: 40180-04-9, the main research area is coumarin anticoagulant ticrynafen interaction.

Ticrynafen (I) [40180-04-9] enhanced the degree of hypoprothrombinemia and altered plasma and hepatic vitamin K epoxide  [25486-55-9] concentrations in warfarin (II) [81-81-2]-treated rats. Ticrynafen did not affect vitamin K-dependent carboxylase  [81181-72-8] or vitamin K epoxide reductase  [55963-40-1] activities in vitro. Cytosolic DT-diaphorase  [9032-20-6] was very sensitive to ticrynafen inhibition in vitro, and inhibition of vitamin K  [12001-79-5] reduction via this enzyme is a possible mechanism by which ticrynafen potentiates coumarin anticoagulant action. Inhibition of this enzyme may also contribute to the reported hepatotoxicity of ticrynafen.

Biochemical Pharmacology published new progress about Blood coagulation. 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

Rudik, A. V. published the artcilePrediction of metabolites of epoxidation reaction in MetaToxdol, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is xenobiotics epoxide metabolite epoxidation reaction MetaTox; AUC, area under the ROC curve; Epoxidation; IAP, invariant accuracy of prediction; LMNA, labelled multilevel neighbourhoods of atom; LOO CV, leave-one-out cross-validation; MNA, multilevel neighbourhoods of atom; PASS; SOE, acute toxicity; SOM, site of metabolism; SoLA, structure with one labelled atom; biotransformation; metabolism; prediction; prediction of activity spectra for substances; reactive metabolite; tienilic acid; toxic metabolite; xenobiotics metabolism.

Biotransformation is a process of the chem. modifications which may lead to the reactive metabolites, in particular the epoxides. Epoxide reactive metabolites may cause the toxic effects. The prediction of such metabolites is important for drug development and ecotoxicol. studies. Epoxides are formed by some oxidation reactions, usually catalyzed by cytochromes P 450, and represent a large class of three-membered cyclic ethers. Identification of mols., which may be epoxidized, and indication of the specific location of epoxide functional group (which is called SOE – site of epoxidation) are important for prediction of epoxide metabolites. Datasets from 355 mols. and 615 reactions were created for training and validation. The prediction of SOE is based on a combination of LMNA (Labeled Multilevel Neighborhood of Atom) descriptors and Bayesian-like algorithm implemented in PASS software and MetaTox web-service. The average invariant accuracy of prediction (AUC) calculated in leave-one-out and 20-fold cross-validation procedures is 0.9. Prediction of epoxide formation based on the created SAR model is included as the component of MetaTox web-service (http://www.way2drug.com/mg)..

SAR and QSAR in Environmental Research published new progress about Biotransformation. 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

David, C. published the artcileSubstrate specificity of the luminal sodium-dependent sulfate transport system in the proximal renal tubule as compared to the contraluminal sulfate exchange system, COA of Formula: C13H8Cl2O4S, the main research area is sulfate transporter specificity kidney proximal tubule.

The efflux of [35S]sulfate from the lumen of the proximal renal tubule into tubular cells of rats was measured by the stop-flow tubular-lumen microperfusion technique. The transport parameters obtained and the apparent Ki values of competing substrates were compared with those of the contraluminal influx of [35S]-sulfate from the interstitium into tubular cells. For the luminal (l) sulfate efflux a Km(l, SO42-) of 0.8 mmol/L and a Jmax(l, SO42-) of 0.2 pmol s-1 cm-1 were found. The corresponding contraluminal (cl) values were Km(cl,SO42-) 2.5 mmol/L and Jmax(cl,SO42-) 1.2 pmol s-1 cm-1. Omission of Na+ from the perfusates reduced the luminal efflux of sulfate by 83%, while the contraluminal influx of sulfate was not changed. The most effective inhibitors of both sulfate transport systems are 8-anilino-1-naphthalenesulfonate, orange G, and H2-DIDS. The data indicate that the Na+-dependent luminal and the Na+-independent contraluminal sulfate transport systems accommodate a similar spectrum of anionic substrates, whereby the inhibitory potency against the luminal Na+-dependent sulfate transport system is identical or smaller than against the contraluminal transporter.

Pfluegers Archiv published new progress about Biological efflux. 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

Naidek, Naiane published the artcileAnchoring conductive polymeric monomers on single-walled carbon nanotubes: towards covalently linked nanocomposites, Recommanded Product: 3-Acetylthiophene, the main research area is anchoring conductive polymeric monomer walled carbon nanotube covalently nanocomposite.

The functionalization of carbon nanotubes (CNTs) has long been a challenge due to the low reactivity of CNTs. Herein we present a novel approach to covalently functionalize CNTs directly on the carbon surface with three different monomers of conductive polymers. A covalently linked polymeric nanocomposite derived from polypyrrole was also obtained. Highly reactive single-walled carbon nanotube (SWCNT) salts were functionalized with the monomers: 3-bromothiophene, 3-acetylthiophene and 1-(2-bromoethyl)-1H-pyrrole. After the functionalization, a “”grafted from”” approach was used to polymerize the pyrrole-derived SWCNTs and obtain a covalently linked polymeric nanocomposite. All samples were characterized by XPS, thermogravimetric anal., SEM, and IR and Raman spectroscopy. Overall, the results evidence the efficiency of the covalent functionalization directly on the skeleton of the SWCNTs, followed by the polymerization and formation of a novel covalently linked nanocomposite. These materials can benefit future optimal applications such as supercapacitors and artificial muscles.

New Journal of Chemistry published new progress about Artificial muscle. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Recommanded Product: 3-Acetylthiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem