Category: benzothiophene

Gross, Aaron D. published the artcileToxicity and synergistic activities of chalcones against Aedes aegypti (Diptera: Culicidae) and Drosophila melanogaster (Diptera: Drosophilidae), Quality Control of 40180-04-9, the main research area is Aedes Drosophila chalcone synergist insecticide; insecticide; larvicide; mosquito; synergist.

Mosquito-borne illnesses are of great concern throughout the world, and chem. insecticides are commonly employed to decrease mosquito populations. However, the developmental insecticide pipeline for vector control has primarily been filled by repurposed agricultural products, and is hampered by their widespread use and insecticide resistance. The present study was performed in the search for new chem. insecticides or insecticide synergists. Screening of 31 chalcone analogs was performed using Aedes aegypti (Linnaeus) first-instar larval toxicity assay, and oral feeding to Drosophila melanogaster’s proper authority should be (Meigen). Synergism studies were performed by topically applying chalcones to adult female Ae. aegypti mosquitoes to examine its impact on activity of carbaryl, which was compared to piperonyl butoxide alone. Fourteen chalcone analogs had LC50 values in the range of 0.4-38ppm against first-instar Ae. aegypti larvae, and three chalcones displayed toxicity against D. melanogaster via feeding (LC50 values ranged from 146-214μg/mL). Two chalcones synergized carbaryl toxicity against adult Ae. aegypti with efficacy similar to piperonyl butoxide. As a result, it is concluded that chalcones may serve as novel insecticides and synergists after further structural optimization.

Journal of Medical Entomology published new progress about Aedes aegypti. 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

Obach, R. Scott published the artcileCan In Vitro Metabolism-Dependent Covalent Binding Data in Liver Microsomes Distinguish Hepatotoxic from Nonhepatotoxic Drugs? An Analysis of 18 Drugs with Consideration of Intrinsic Clearance and Daily Dose, COA of Formula: C13H8Cl2O4S, the main research area is drug hepatotoxicity screening metabolism covalent binding liver.

In vitro covalent binding assessments of drugs have been useful in providing retrospective insights into the association between drug metabolism and a resulting toxicol. response. On the basis of these studies, it has been advocated that in vitro covalent binding to liver microsomal proteins in the presence and the absence of NADPH be used routinely to screen drug candidates. However, the utility of this approach in predicting toxicities of drug candidates accurately remains an unanswered question. Importantly, the years of research that have been invested in understanding metabolic bioactivation and covalent binding and its potential role in toxicity have focused only on those compounds that demonstrate toxicity. Investigations have not frequently queried whether in vitro covalent binding could be observed with drugs with good safety records. Eighteen drugs (nine hepatotoxins and nine nonhepatotoxins in humans) were assessed for in vitro covalent binding in NADPH-supplemented human liver microsomes. Of the two sets of nine drugs, seven in each set were shown to undergo some degree of covalent binding. Among hepatotoxic drugs, acetaminophen, carbamazepine, diclofenac, indomethacin, nefazodone, sudoxicam, and tienilic acid demonstrated covalent binding, while benoxaprofen and felbamate did not. Of the nonhepatotoxic drugs evaluated, buspirone, diphenhydramine, meloxicam, paroxetine, propranolol, raloxifene, and simvastatin demonstrated covalent binding, while ibuprofen and theophylline did not. A quant. comparison of covalent binding in vitro intrinsic clearance did not sep. the two groups of compounds, and in fact, paroxetine, a nonhepatotoxin, showed the greatest amount of covalent binding in microsomes. Including factors such as the fraction of total metabolism comprised by covalent binding and the total daily dose of each drug improved the discrimination between hepatotoxic and nontoxic drugs based on in vitro covalent binding data; however, the approach still would falsely identify some agents as potentially hepatotoxic.

Chemical Research in Toxicology published new progress about Covalent bond. 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

Melet, Armelle published the artcileSubstrate selectivity of human cytochrome P450 2C9: importance of residues 476, 365, and 114 in recognition of diclofenac and sulfaphenazole and in mechanism-based inactivation by tienilic acid, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is substrate recognition cytochrome P450 2C9 diclofenac sulfaphenazole tienilic acid.

A series of six site-directed mutants of CYP 2C9 were constructed with the aim to better define the amino acid residues that play a critical role in substrate selectivity of CYP 2C9, particularly in three distinctive properties of this enzyme: (i) its selective mechanism-based inactivation by tienilic acid (TA), (ii) its high affinity and hydroxylation regioselectivity toward diclofenac, and (iii) its high affinity for the competitive inhibitor sulfaphenazole (SPA). The S365A mutant exhibited kinetic characteristics for the 5-hydroxylation of TA very similar to those of CYP 2C9; however, this mutant did not undergo any detectable mechanism-based inactivation by TA, which indicates that the OH group of Ser 365 could be the nucleophile forming a covalent bond with an electrophilic metabolite of TA in TA-dependent inactivation of CYP 2C9. The F114I mutant was inactive toward the hydroxylation of diclofenac; moreover, detailed analyses of its interaction with a series of SPA derivatives by difference visible spectroscopy showed that the high affinity of SPA to CYP 2C9 (Ks=0.4 μM) was completely lost when the Ph substituent of Phe 114 was replaced with the alkyl group of Ile (Ks=190±20 μM), or when the Ph substituent of SPA was replaced with a cyclohexyl group (Ks=120±30 μM). However, this cyclohexyl derivative of SPA interacted well with the F114I mutant (Ks=1.6±0.5 μM). At the opposite end, the F94L and F110I mutants showed properties very similar to those of CYP 2C9 toward TA and diclofenac. Finally, the F476I mutant exhibited at least three main differences compared to CYP 2C9: (i) big changes in the kcat and Km values for TA and diclofenac hydroxylation, (ii) a 37-fold increase of the Ki value found for the inhibition of CYP 2C9 by SPA, and (iii) a great change in the regioselectivity of diclofenac hydroxylation, the 5-hydroxylation of this substrate by CYP 2C9 F476I exhibiting a kcat of 28 min-1. These data indicate that Phe 114 plays an important role in recognition of aromatic substrates of CYP 2C9, presumably via Π-stacking interactions. They also provide the first exptl. evidence showing that Phe 476 plays a crucial role in substrate recognition and hydroxylation by CYP 2C9.

Archives of Biochemistry and Biophysics published new progress about Covalent bond. 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, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Chen, Minjun published the artcileA Model to predict severity of drug-induced liver injury in humans, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is human drug liver injury.

Drug-induced liver injury (DILI) is a major public health concern, and improving its prediction remains an unmet challenge. Recently, we reported the Rule-of-2 (RO2) and found lipophilicity (logP ≥3) and daily dose ≥100 mg of oral medications to be associated with significant risk for DILI; however, the RO2 failed to estimate grades of DILI severity. In an effort to develop a quant. metrics, we analyzed the association of daily dose, logP, and formation of reactive metabolites (RM) in a large set of Food and Drug Administration-approved oral medications and found factoring RM into the RO2 to highly improve DILI prediction. Based on these parameters and by considering n = 354 drugs, an algorithm to assign a DILI score was developed. In univariate and multivariate logistic regression analyses the algorithm (i.e., DILI score model) defined the relative contribution of daily dose, logP, and RM and permitted a quant. assessment of risk of clin. DILI. Furthermore, a clear relationship between calculated DILI scores and DILI risk was obtained when applied to three independent studies. The DILI score model was also functional with drug pairs defined by similar chem. structure and mode of action but divergent toxicities. Specifically, for drug pairs where the RO2 failed, the DILI score correctly identified toxic drugs. Finally, the model was applied to n = 159 clin. cases collected from the National Institutes of Health’s LiverTox database to demonstrate that the DILI score correlated with the severity of clin. outcome. Conclusions: Based on daily dose, lipophilicity, and RM, a DILI score algorithm was developed that provides a scale of assessing the severity of DILI risk in humans associated with oral medications. (Hepatol. 2016;64:931-940).

Hepatology (Hoboken, NJ, United States) published new progress about Drug toxicity. 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

Darnell, Malin published the artcileSignificantly Different Covalent Binding of Oxidative Metabolites, Acyl Glucuronides, and S-Acyl CoA Conjugates Formed from Xenobiotic Carboxylic Acids in Human Liver Microsomes, Related Products of benzothiophene, the main research area is metabolite acyl glucuronide xenobiotic human liver microsome.

Xenobiotic carboxylic acids may be metabolized to oxidative metabolites, acyl glucuronides, and/or S-acyl-CoA thioesters (CoA conjugates) in vitro, e.g., in hepatocytes, and in vivo. These metabolites can potentially be reactive species and bind covalently to tissue proteins and are generally considered to mediate adverse drug reactions in humans. Acyl glucuronide metabolites have been the focus of reactive metabolite research for decades, whereas drug-CoA conjugates, which have been shown to be up to 40-70 times more reactive, have been given much less attention. In an attempt to dissect the contribution of different pathways to covalent binding, we utilized human liver microsomes supplemented with NADPH, uridine 5′-diphosphoglucuronic acid (UDPGA), or CoA to evaluate the reactivity of each metabolite sep. Seven carboxylic acid drugs were included in this study. While ibuprofen and tolmetin are still on the market, ibufenac, fenclozic acid, tienilic acid, suprofen, and zomepirac were stopped before their launch or withdrawn. The reactivities of the CoA conjugates of ibuprofen, ibufenac, fenclozic acid, and tolmetin were higher compared to those of their corresponding oxidative metabolites and acyl glucuronides, as measured by the level of covalent binding to human liver microsomal proteins. The highest covalent binding was observed for ibuprofenyl-CoA and ibufenacyl-CoA, to levels of 1000 and 8600 pmol drug eq/mg protein, resp. In contrast and in agreement with the proposed P 450-mediated toxicity for these drug mols., the reactivities of oxidative metabolites of suprofen and tienilic acid were higher compared to the reactivities of their conjugated metabolites, with NADPH-dependent covalent binding of 250 pmol drug eq/mg protein for both drugs. The seven drugs all formed UDPGA-dependent acyl glucuronides, but none of these resulted in covalent binding. This study shows that, unlike studies with hepatocytes or in vivo, human liver microsomes provide an opportunity to investigate the reactivity of individual metabolites.

Chemical Research in Toxicology published new progress about Drug toxicity. 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, Related Products of benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Beaune, Philippe H. published the artcileImmunotoxicology of the liver: adverse reactions to drugs, Category: benzothiophene, the main research area is liver immunotoxicol drug adverse reaction review.

A review, with 45 references Liver is a frequent target for drug-induced hepatitis. They can be classified in two categories: the hepatitis in which the drug or a metabolite reach a vital target in the cell and the hepatitis in which the drug triggers an adverse immune response directed against the liver. We will discuss essentially this second kind of disease. They have key clin. features such as the low frequency, the dose independence, the delay between the beginning of drug intake and the triggering of the disease, the shortening of the delay upon rechallenge and very often the presence of autoantibodies in the serum of the patients. Such signs were found in hepatitis triggered by drugs such as halothane, tienilic acid, dihydralazine, anticonvulsants. They will be taken as examples to show the recent progress in the understanding of the mechanisms leading to the disease. It has been postulated that the drug is metabolized into a reactive metabolite binding to the enzyme which generated it; therefore the neoantigen might trigger an immune response characterized by the production of antibodies recognizing the native and or the modified protein. Most of these steps were proven in the cases of halothane, tienilic acid and dihydralazine. Several points seem important in the development of the disease: the equilibrium between toxication and detoxication pathways, the nature and amount of neoantigen, the individual immune response. However, many points remain unclear: for instance, the reason for the very low frequency of this kind of disease; the precise mechanism of the adverse immune response; the risk factors for developing such adverse reactions. Efforts should be made to better understand the mechanisms of this kind of disease: for instance, an animal model, tests to identify drugs at risk for such reactions, the role of these drugs in the processing of P450s and the processing of the neoantigens for their presentation to the immune system.

Journal of Hepatology published new progress about Drug toxicity. 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

Mansuy, Daniel published the artcileMolecular structure and hepatotoxicity: compared data about two closely related thiophene compounds, Related Products of benzothiophene, the main research area is review thiophene compound hepatotoxicity metabolism structure; cytochrome P450 thiophene metabolism hepatotoxicity review; tienilic acid isomer hepatotoxicity structure review.

A review with 11 references Two closely related compounds, a diuretic drug tienilic acid (TA) and its isomer TAI have been found to exert very different toxic effects. In human liver microsomes TA is oxidized mainly by CYP 2C9 with formation of a reactive metabolite which covalently binds to CYP 2C9 in a rather specific manner. On the contrary, CYP 2C9-dependent oxidation of TAI leads to reactive metabolite(s) causing an intense covalent binding to several microsomal proteins. Based on these very different behaviors and fates of TA and TAI metabolites, it is proposed that the direct hepatotoxic effects of TAI could be due to an intense, non-specific covalent binding of its reactive metabolite(s) to liver proteins, whereas the toxic effects of the immunoallergic type of TA could be due to the very specific covalent binding of its sulfoxide metabolite to CYP 2C9.

Journal of Hepatology published new progress about Drug toxicity. 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, Related Products of benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Ramachandran, P. Veeraraghavan published the artcileTiCl4-Catalyzed Hydroboration of Ketones with Ammonia Borane, Formula: C6H6OS, the main research area is secondary alc preparation; ketone titanium chloride ammonia borane hydroboration reduction.

Investigation of a variety of Lewis acids for the hydroboration-hydrolysis (reduction) of ketones with amine-boranes has revealed that catalytic (10 mol %) titanium tetrachloride (TiCl4) in di-Et ether at room temperature immensely accelerates the reaction of ammonia borane. The product alcs. are produced in good to excellent yields within 30 min, even with ketones which typically requires 24 h or longer to reduce under uncatalyzed conditions. Several potentially reactive functionalities are tolerated, and substituted cycloalkanones are reduced diastereoselectively to the thermodn. product. A deuterium labeling study and 11B NMR anal. of the reaction have been performed to verify the proposed hydroboration mechanism.

Journal of Organic Chemistry published new progress about Hydroboration. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Formula: C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Odlind, Bo published the artcileTubular secretion and effects of tienilic acid in the hen, Product Details of C13H8Cl2O4S, the main research area is tienilic acid kidney tubule secretion.

The relationship between renal tubular secretion of the uricosuric diuretic tienilic acid (I) [40180-04-9] (10 or 30 μg/kg/min) and its saluretic effects was determined in hens using a modified Sperber technique. A true tubular excretion fraction (TTEF) of 29.9% (mean) for tienilic acid was reduced by novobiocin to 3.3%. This demonstrates active tubular secretion of the diuretic by an organic anion transport system in the hen kidney. Infusion of the diuretic into one leg vein caused a marked ipsilateral excess excretion of Cl-, Na+, and K+; these effects were reduced by novobiocin. Thus, in the hen a significant part of the saluretic effect of tienilic acid depends on the active secretion of the drug by tubular cells, as has previously been found for 3 loop diuretics i.e. ethacrynic acid, furosemide and piretanide. Apparently, the saluretic effect of tienilic acid is evoked mainly from the luminal side of the avian nephron. At an infusion rate of 20 μg/kg/min of tienilic acid, a marked saluresis occurred; there was, however, no effect on the urinary urate excretion.

European Journal of Pharmacology published new progress about Kidney tubule. 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

Pinkert, Tobias published the artcileUse of Strain-Release for the Diastereoselective Construction of Quaternary Carbon Centers, Safety of 3-Acetylthiophene, the main research area is methoxyiminoethyl arene bicyclobutanone ethyl glyoxylate rhodium catalyst three component; hydroxy methoxyiminoethyl arylvinyl succinate preparation diastereoselective.

The formation of quaternary carbon centers with excellent diastereoselectivity via a strain-release protocol were discussed. An organometallic species was generated by Cp*Rh(III)-catalyzed C-H activation, which was then coupled with strained bicyclobutanes (BCBs) and a prochiral carbon electrophile in a three-component reaction. A rare example of BCBs in transition metal catalysis and demonstrates their broad potential to access novel reaction pathways were illustrated. The method developed exhibited a ample functional group tolerance, and the obtained products were further transformed into valuable α-quaternary β-lactones. Preliminary mechanistic investigations suggested a two fold C-C bond cleavage sequence involving σ-bond insertion and an ensuing β-carbon elimination event.

Journal of the American Chemical Society published new progress about Alkenylation. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Safety of 3-Acetylthiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem