Category: benzothiophene

Li, Weina published the artcileVisible-Light-Promoted Carbene Insertion and Decarbonylation for the Synthesis of α-Substituted γ-Ketoesters, Product Details of C6H6OS, the main research area is ketoester green preparation; enaminone diazoester carbene insertion decarbonylation visible light promoted.

Herein, a blue visible-light-promoted approach to prepare a variety of α-substituted γ-ketoesters derivatives RC(O)CH2C(COOR1)R2R3 [R = Ph, 3-FC6H4, 4-MeC6H4, etc.; R1 = Me, Et; R2 = H, CHO; R3 = Ph, 4-ClC6H4, 3-thienyl, etc.] through carbene insertion and the decarbonylation of enaminones and diazoesters was reported. These reactions used readily available starting materials, as well as transition-metal-free, eco-friendly procedures that were amenable to gram-scale synthesis and wide functional group tolerance. This methodol. might be useful for constructing polysubstituted heterocycles with potential biol. activity.

Journal of Organic Chemistry published new progress about Decarbonylation. 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

Rattie, Elisabeth S. published the artcileA dissolution anomaly involving ticrynafen in simulated intestinal fluid without enzyme, HPLC of Formula: 40180-04-9, the main research area is ticrynafen dissolution intestinal fluid; potassium ticrynafen dissolution.

Data are presented showing that the anomalous dissolution behavior of ticrynafen (I) [40180-04-9] in simulated intestinal fluid without enzyme is due to the presence of K+ in the dissolution medium. Solubility studies indicate that an insoluble 1:1 complex is formed between I and I K salt [81943-63-7]. This complex apparently creates an insoluble barrier that prevents complete dissolution of I. To determine whether this might also occur in clin. use, a 3-way cross-over study in 12 subjects was done. Concomitant administration of I tablets and K in the form of a com. supplement does not adversely affect bioavailability.

Journal of Pharmaceutical Sciences published new progress about Digestive tract. 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

Preusch, Peter C. published the artcileVitamin K1 2,3-epoxide and quinone reduction: mechanism and inhibition, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is vitamin K1 epoxide quinone reduction microsome; reductase vitamin K epoxide microsome; DT diaphorase vitamin K metabolism microsome.

The chem. and enzymic pathways of vitamin K1 epoxide and quinone reduction have been investigated. Na borohydride treatment resulted in carbonyl reduction generating relatively stable compounds that did not proceed to quinone in the presence of base. NAD(P)H:quinone oxidoreductase (DT-diaphorase) reduction of vitamin K to the hydroquinone was a significant process in intact microsomes, but 1/5th the rate of the dithiothreitol (DTT)-dependent reduction No evidence was found for DT-diaphorase catalyzed reduction of vitamin K1 epoxide, nor was it capable of mediating transfer of electrons from NADH to the microsomal epoxide reducing enzyme. Purified diaphorase reduced detergent-solubilized vitamin K1 10-5 as rapidly as it reduced dichlorophenylindophenol (DCPIP). Reduction of 10 μM vitamin K1 by 200 μM NADH was not inhibited by 10 μM dicoumarol, whereas DCPIP reduction was fully inhibited. In contrast to vitamin K3 (menadione), vitamin K1 (phylloquinone) did not stimulate microsomal NADPH consumption in the presence or absence of dicoumarol. DTT-dependent vitamin K epoxide reduction and vitamin K reduction were shown to be mutually inhibitory reactions, suggesting that both occur at the same enzymic site. On this basis, a mechanism for reduction of the quinone by thiols is proposed. Both the DTT-dependent reduction of vitamin K1 epoxide and quinone, and the reduction of DCPIP by purified DT-diaphorase were inhibited by dicoumarol, warfarin, lapachol, and sulfaquinoxaline.

Free Radical Research Communications published new progress about Disulfide group. 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

Uetrecht, Jack published the artcileRole of drug metabolism for breaking tolerance and the localization of drug hypersensitivity, Application In Synthesis of 40180-04-9, the main research area is review drug reactive metabolite tolerance hypersensitivity penicillamine nevirapine modeling.

There are 3 major working hypotheses for the mechanism of drug hypersensitivity reactions: the hapten hypotheses, the danger hypothesis and the PI hypothesis. These hypotheses are difficult to test because of the idiosyncratic nature of hypersensitivity reactions. There is evidence that reactive metabolites are involved in many hypersensitivity reactions, and the reactive metabolite is often formed in the target organ of toxicity, presumably because the half-life of most reactive metabolites is too short to allow them to reach distant sites. In the case of less reactive species that freely circulate the pattern of hypersensitivity usually fits that expected of an extracellular antigen, specifically, an antibody-mediated reaction. The authors have used 2 animal models: penicillamine-induced autoimmunity and nevirapine-induced skin rash in Brown Norway rats to test hypotheses. The authors have found that tolerance is readily induced with a lower dose of the drug, although the nature of tolerance is different in the 2 models. In the penicillamine model, tolerance is immune-mediated and can be overcome by agents that act as a danger signal. Reactive metabolites may also act as a danger signal. The models can also be used to test the role of reactive species in the mechanism of hypersensitivity reactions.

Toxicology published new progress about Drug metabolism. 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

Gramec, Darja published the artcileBioactivation Potential of Thiophene-Containing Drugs, SDS of cas: 40180-04-9, the main research area is review thiophene derivative metabolism hepatotoxicity.

Thiophene is a five-membered, sulfur-containing heteroaromatic ring commonly used as a building block in drugs. It is considered to be a structural alert, as its metabolism can lead to the formation of reactive metabolites. Thiophene S-oxides and thiophene epoxides are highly reactive electrophilic thiophene metabolites whose formation is cytochrome P 450-dependent. These reactive thiophene-based metabolites are quite often responsible for drug-induced hepatotoxicity. Tienilic acid is an example of a thiophene-based drug that was withdrawn from the market after only a few months of use, due to severe cases of immune hepatitis. However, inclusion of the thiophene moiety in drugs does not necessarily result in toxic effects. The presence of other, less toxic metabolic pathways, as well as an effective detoxification system in our body, protects us from the bioactivation potential of the thiophene ring. Thus, the presence of a structural alert itself is insufficient to predict a compound’s toxicity. The question therefore arises as to which factors significantly influence the toxicity of thiophene-containing drugs. There is no easy way to answer this question. However, the findings presented here indicate that, for a number of reasons, daily dose and alternative metabolic pathways are important factors when predicting toxicity and will therefore be discussed together with examples.

Chemical Research in Toxicology published new progress about Drug metabolism. 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

Masubuchi, Noriko published the artcilePrediction of in Vivo Potential for Metabolic Activation of Drugs into Chemically Reactive Intermediate: Correlation of in Vitro and in Vivo Generation of Reactive Intermediates and in Vitro Glutathione Conjugate Formation in Rats and Humans, Formula: C13H8Cl2O4S, the main research area is drug metabolic activation glutathione conjugate formation toxicity.

The covalent binding of reactive intermediates to macromols. might have potential involvement in severe adverse drug reactions. Thus, quantification of reactive metabolites is necessary during the early stage of drug discovery to avoid serious toxicity. In this study, the relation between covalent binding and glutathione (GSH) conjugate formation in rat and human liver microsomes were investigated using 10 representative radioactive compounds that have been reported as hepatotoxic or having other toxicity derived from their reactive intermediates: acetaminophen, amodiaquine, carbamazepine, clozapine, diclofenac, furosemide, imipramine, indomethacin, isoniazid, and tienilic acid, all at a concentration of 10 μM. The GSH conjugate formation rate correlates well with the covalent binding of radioactivity (both rat and human, r2 = 0.93), which suggests that quantification of the GSH conjugate can be used to estimate covalent binding. To quantify the GSH-conjugation rate with non-radiolabeled compounds in vitro, the validation study for the determination of GSH conjugate formation using 35S-GSH by radio-HPLC was useful to predict metabolic activation. Following oral administration of 20 mg/kg of the radiolabeled compounds to rats, radioactivity that covalently bound to plasma and liver proteins was determined The in vivo maximum covalent binding level in liver based on the free fraction of plasma area under the concentration curve (AUC) and in vitro covalent binding rate was found to correlate well (r2 = 0.79). Therefore, this model for in vitro covalent binding studies in human and rat and in vivo rat studies might be useful in predicting human metabolic activation of compounds

Chemical Research in Toxicology published new progress about Drug metabolism. 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

Yu, Ke published the artcileHigh daily dose and being a substrate of cytochrome P450 enzymes are two important predictors of drug-induced liver injury, HPLC of Formula: 40180-04-9, the main research area is drug induced liver injury cytochrome P450.

Drug-induced liver injury (DILI) is complicated and difficult to predict. It has been observed that drugs with extensive hepatic metabolism have a higher likelihood of causing DILI. Cytochrome P 450 (P 450) enzymes are primarily involved in hepatic metabolism Identifying the associations of DILI with drugs that are P 450 substrates, inhibitors, or inducers will be extremely helpful to clinicians during the decision-making process of caring for a patient suspected of having DILI. We collected metabolism data on P 450 enzymes for 254 orally administered drugs in the Liver Toxicity Knowledge Base Benchmark Dataset with a known daily dose, and applied logistic regression to identify these associations We revealed that drugs that are substrates of P 450 enzymes have a higher likelihood of causing DILI [odds ratio (OR), 3.99; 95% confidence interval (95% CI), 2.07-7.67; P < 0.0001], which is dose-independent, and drugs that are P 450 inhibitors have a higher likelihood of generating DILI only when they are administered at high daily doses (OR, 6.03; 95% CI, 1.32-27.5; P = 0.0098). However, drugs that are P 450 inducers are not observed to be associated with DILI (OR, 1.55; 95% CI, 0.65-3.68; P = 0.3246). Our findings will be useful in identifying the suspected medication as a cause of liver injury in clin. settings. Drug Metabolism & Disposition published new progress about Drug metabolism. 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

Tay, Suzanne published the artcileMechanistic studies of the cationic binding pocket of CYP2C9 in vitro and in silico: metabolism of nonionizable analogs of tienilic acid, HPLC of Formula: 40180-04-9, the main research area is CYP2C9 tienilic acid metabolism liver microsome.

Tienilic acid (TA) is selectively oxidized at the C-5 position of the thiophene ring by the human liver enzyme cytochrome P 450 2C9 (CYP2C9). This oxidation is mediated by the proximal positioning of the thiophene over the heme iron, which is proposed to be coordinated by an interaction of the TA carboxylic acid to a cationic binding pocket in the enzyme active site. In this study, we investigated how chem. modification of TA influences the bioactivation by CYP2C9. For this investigation, nine analogs of TA were chosen with substitutions on either side of the mol. We tested three parameters, including CYP2C9 inhibition, metabolic profiling, and in silico docking. Of the 10 compounds tested, only two (TA and a noncarboxyl analog) resulted in competitive and time-dependent inhibition of CYP2C9. Metabolic profiling revealed a trend in which substitution of the carboxylate with nonionizable functional groups resulted in metabolic switching from oxidation of the aromatic ring to dealkylation reactions at the opposite side of the structure. The in silico modeling predicted an opposite binding orientation to that of TA for many analogs, including the 3-thenoyl regio-isomer analog, which contradicts previous models. Together these data show that disrupting interactions with the cationic binding pocket of CYP2C9 will impact the sites of metabolism and inhibition of the enzyme.

Drug Metabolism & Disposition published new progress about Drug metabolism. 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

Berry, Loren M. published the artcileDynamic modeling of cytochrome P450 inhibition in vitro: impact of inhibitor depletion on IC50 shift, HPLC of Formula: 40180-04-9, the main research area is CYP3A4 CYP2C9 CYP2D6 protein inhibitor liver microsome clarithromycin dasatinib.

The impact of inhibitor depletion on the determination of shifted IC50 (IC50 determined after 30 min of preincubation with inhibitor) is examined In addition, IC50-shift data are analyzed using a mechanistic model that incorporates the processes of inhibitor depletion, as well as reversible and time-dependent inhibition. Anomalies such as a smaller-than-expected shift in IC50 and even increases in IC50 with preincubation were explained by the depletion of inhibitor during the preincubation. The IC50-shift assay remains a viable approach to characterizing a wide range of reversible and time-dependent inhibitors. However, as with more traditional time-dependent inactivation methods, it is recommended that IC50-shift exptl. data be interpreted with some knowledge of the magnitude of inhibitor depletion. For the most realistic classification of time-dependent inhibitors using IC50-shift methods, shifted IC50 should be calculated using observed inhibitor concentrations at the end of the incubation rather than nominal inhibitor concentrations Finally, a mechanistic model that includes key processes, such as competitive inhibition, enzyme inactivation, and inhibitor depletion, can be used to describe accurately the observed IC50 and shifted IC50 curves. For compounds showing an IC50 fold shift >1.5 based on the observed inhibitor concentrations, reanalyzing the IC50-shift data using the mechanistic model appeared to allow for reasonable estimation of KI, KI, and kinact directly from the IC50 shift experiments

Drug Metabolism & Disposition published new progress about Drug metabolism. 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

Sheridan, Robert P. published the artcileEmpirical Regioselectivity Models for Human Cytochromes P450 3A4, 2D6, and 2C9, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is QSAR regioselectivity model cytochrome P450 isoform drug metabolism.

Cytochromes P 450 3A4, 2D6, and 2C9 metabolize a large fraction of drugs. Knowing where these enzymes will preferentially oxidize a mol., the regioselectivity, allows medicinal chemists to plan how best to block its metabolism The authors present QSAR-based regioselectivity models for these enzymes calibrated against compiled literature data of drugs and drug-like compounds These models are purely empirical and use only the structures of the substrates, in contrast to those models that simulate a specific mechanism like hydrogen radical abstraction, and/or use explicit models of active sites. The authors most predictive models use three substructure descriptors and two phys. property descriptors. Descriptor importance from the random forest QSAR method show that other factors than the immediate chem. environment and the accessibility of the hydrogen affect regioselectivity in all three isoforms. The cross-validated predictions of the models are compared to predictions from the authors earlier mechanistic model (Singh et al. J. Med. Chem. 2003, 46, 1330-1336) and predictions from MetaSite (Cruciani et al. J. Med. Chem. 2005, 48, 6970-6979).

Journal of Medicinal Chemistry published new progress about Drug metabolism. 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