Category: benzothiophene

Garay, Ricardo P. published the artcileStimulation of potassium fluxes by diuretic drugs in human red cells, COA of Formula: C13H8Cl2O4S, the main research area is diuretic potassium transport erythrocyte.

Two different classes of diuretic drugs consisting of (aryloxy)acetic acid diuretics, including ethacrynic acid  [58-54-8], tienilic acid  [40180-04-9], and (-)-indacrinone  [57297-16-2], and furopyridine diuretics, including (±)-BN 50157 (I) [91868-80-3] and (±)-cycletanide  [89943-82-8], stimulate K+ movement across human red cell membranes. The kinetic properties of this effect (K+-specificity, saturability, optical isomerism, antagonism by structural analogs, etc.) strongly suggest that it is mediated by a K+-transport system with a specific binding site for some diuretic drugs. The stimulated K+ fluxes are resistant to ouabain, bumetanide, and quinine, thus suggesting that they are not mediated by the Na+, K+-pump, Na+, K+-cotransport or by the Ca2+-dependent K+-permeability (Gardos effect). The replacement of Cl- by NO3- ions can either decrease, increase or have no effect on the stimulated K+ fluxes, depending on the diuretic drug. Apparently, the K+ fluxes are not mediated by stimulation of a Cl–dependent K+ carrier. The study of structural analogs of I showed that the intensity of the stimulation of K+ fluxes is strongly correlated with the magnitude of the natriuretic effect. Curiously, some antiallergic furopyridines are able to inhibit K+ fluxes.

Biochemical Pharmacology published new progress about Biological transport. 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

Rossato, Gianluca published the artcileProbing Small-Molecule Binding to Cytochrome P450 2D6 and 2C9: An In Silico Protocol for Generating Toxicity Alerts, Related Products of benzothiophene, the main research area is pharmacophore QSAR metabolism CYP2D6 CYP2C9 binding screening interaction toxicity.

Drug metabolism, toxicity, and their interaction profiles are major issues in the drug-discovery and lead-optimization processes. The cytochromes P 450 (CYPs) 2D6 and 2C9 are enzymes involved in the oxidative metabolism of a majority of marketed drugs. Therefore, the prediction of the binding affinity towards CYP2D6 and CYP2C9 would be beneficial for identifying cytochrome-mediated adverse effects triggered by drugs or chems. (e.g., toxic reactions, drug-drug, and food-drug interactions). By identifying the binding mode by using pharmacophore prealignment, automated flexible docking, and by quantifying the binding affinity by multidimensional QSAR (mQSAR), we validated a model family of 56 compounds (46 training, 10 test) and 85 compounds (68 training, 17 test) for CYP2D6 and CYP2C9, resp. The correlation with the exptl. data (cross-validated r2=0.811 for CYP2D6 and 0.687 for CYP2C9) suggests that our approach is suited for predicting the binding affinity of compounds towards CYP2D6 and CYP2C9. The models were challenged by Y-scrambling and by testing an external dataset of binding compounds (15 compounds for CYP2D6 and 40 for CYP2C9). To assess the probability of false-pos. predictions, datasets of nonbinders (64 compounds for CYP2D6 and 56 for CYP2C9) were tested by using the same protocol. The two validated mQSAR models were subsequently added to the VirtualToxLab (VTL, ).

ChemMedChem published new progress about Drug interactions, adverse. 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

Han, Zhengyu published the artcileEnantiodivergent Synthesis of Chiral Tetrahydroquinoline Derivatives via Ir-Catalyzed Asymmetric Hydrogenation: Solvent-Dependent Enantioselective Control and Mechanistic Investigations, COA of Formula: C6H6OS, the main research area is chiral tetrahydroquinoline preparation enantioselective; quinoline hydrogenation iridium catalyst.

Ir-catalyzed asym. hydrogenation of quinolines I (R = Me, Ph, naphthalen-2-yl, 2H-1,3-benzodioxol-5-yl, thiophen-3-yl, etc.; R1 = H, Me, Et, n-Pr; R2 = H, 5-Cl, 6-OMe, 7-Me, etc.) was developed, and both enantiomers of chiral tetrahydroquinoline derivatives ((R)/(S)/cis/trans)-II could be easily obtained, resp., in high yields with good enantioselectivities through the adjustment of reaction solvents (toluene/dioxane: up to 99% yield, 98% ee (R), TON = 680; EtOH: up to 99% yield, 94% ee (S), TON = 1680). It provided an efficient and simple synthetic strategy for the enantiodivergent synthesis of chiral tetrahydroquinolines ((R)/(S)/cis/trans)-II, and gram-scale asym. hydrogenation proceeded well with low-catalyst loading in these two reaction systems. A series of deuterium-labeling experiments, control experiments, and 1H NMR and electrospray ionization-mass spectrometry experiments have been conducted, and a reasonable and possible reaction process was revealed on the basis of these useful observations.

ACS Catalysis published new progress about Enantioselective synthesis. 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

Lim, Heng-Keang published the artcileAutomated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is inactivation cytochrome CYP3A4 CYP2C9 CYP2C19 CYP2D6 CYP1A2 microsome.

A strategy is proposed to profile compounds for mechanism-based inactivation of CYP3A4, CYP2C19, CYP2C9, CYP2D6, and CYP1A2 based on an apparent partition ratio screen. Potent positives from the screen are confirmed by time- and concentration-dependent inactivation assays. Quasi-irreversible inhibitions are then differentiated from irreversible inactivations by oxidation with potassium ferricyanide and/or dialysis. The three-step screening procedure has been validated with acceptable accuracy and precision for detection and confirmation of mechanism-based inactivators in drug discovery. We report here the apparent partition ratios for 19 mechanism-based inactivators and four quasi-irreversible inhibitors obtained under the same exptl. conditions. The apparent partition ratio screen was automated to provide throughput for determining structure-mechanism-based inactivation relationships. Information about reversibility can be used to assess potential toxicity mediated by covalent adducts, as well as the potential for pharmacokinetic drug-drug interactions. Direct comparison of known mechanism-based inactivators and quasi-irreversible inhibitors, based on our screening of apparent partition ratios, has identified ritonavir, mibefradil, and azamulin as highly effective mechanism-based inactivators; e.g., 1 mol of CYP3A4 was inactivated on turnover of about 2 mol of compound Other mechanism-based inactivators we identified include bergamottin (CYP1A2 besides previously reported CYP3A4), troglitazone (CYP3A4), rosiglitazone (CYP3A4), and pioglitazone (CYP3A4). Comparison of the apparent partition ratios and inactivation clearance data for the three glitazones suggests that the chromane moiety on troglitazone contributes to its greater potency for mechanism-based inactivation.

Drug Metabolism and Disposition published new progress about Enzyme inhibition kinetics. 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

Ha-Duong, Nguyet-Thanh published the artcileTiclopidine as a Selective Mechanism-Based Inhibitor of Human Cytochrome P450 2C19, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is ticlopidine inhibition cytochrome P450 2C19.

Experiments using recombinant yeast-expressed human liver cytochromes P 450 confirmed previous literature data indicating that ticlopidine is an inhibitor of CYP 2C19. The present studies demonstrated that ticlopidine is selective for CYP 2C19 within the CYP 2C subfamily. UV-visible studies on the interaction of a series of ticlopidine derivatives with CYP 2C19 showed that ticlopidine binds to the CYP 2C19 active site with a Ks value of 2.8 ± 1 μM. Derivatives that do not involve either the o-chlorophenyl substituent, the free tertiary amine function, or the thiophene ring of ticlopidine did not lead to such spectral interactions and failed to inhibit CYP 2C19. Ticlopidine is oxidized by CYP 2C19 with formation of two major metabolites, the keto tautomer of 2-hydroxyticlopidine (1) and the dimers of ticlopidine S-oxide (TSOD) (Vmax = 13 ± 2 and 0.4 ± 0.1 min-1). During this oxidation, CYP 2C19 was inactivated; the rate of its inactivation was time and ticlopidine concentration dependent. This process meets the chem. and kinetic criteria generally accepted for mechanism-based enzyme inactivation. It occurs in parallel with CYP 2C19-catalyzed oxidation of ticlopidine, is inhibited by an alternative well-known substrate of CYP 2C19, omeprazole, and correlates with the covalent binding of ticlopidine metabolite(s) to proteins. Moreover, CYP 2C19 inactivation is not inhibited by the presence of 5 mM glutathione, suggesting that it is due to an alkylation occurring inside the CYP 2C19 active site. The effects of ticlopidine on CYP 2C19 are very analogous with those previously described for the inactivation of CYP 2C9 by tienilic acid. This suggests that a similar electrophilic intermediate, possibly a thiophene S-oxide, is involved in the inactivation of CYP 2C19 and CYP 2C9 by ticlopidine and tienilic acid, resp. The kinetic parameters calculated for ticlopidine-dependent inactivation of CYP 2C19, i.e., t1/2max = 3.4 min, kinact = 3.2 10-3 s-1, KI = 87 μM, kinact/KI = 37 L·mol-1·s-1, and r (partition ratio) = 26 (in relation with formation of 1 + TSOD), classify ticlopidine as an efficient mechanism-based inhibitor although somewhat less efficient than tienilic acid for CYP 2C9. Importantly, ticlopidine is the first selective mechanism-based inhibitor of human liver CYP 2C19 and should be a new interesting tool for studying the topol. of the active site of CYP 2C19.

Biochemistry published new progress about Enzyme inhibition kinetics. 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

Food and Drug Administration, HHS published the artcileList of drug products that have been withdrawn or removed from the market for reasons of safety or effectiveness, SDS of cas: 40180-04-9, the main research area is drug safety effectiveness standard.

The Food and Drug Administration (FDA) is amending its regulations to include a list of drug products that may not be used for pharmacy compounding under the exemptions under section 503A of the Federal Food, Drug, and Cosmetic Act because they have had their approval withdrawn or were removed from the market because the drug product or its components have been found to be unsafe or not effective. The list has been compiled under the new statutory requirements of the Food and Drug Administration Modernization Act of 1997 (Modernization Act).

Federal Register published new progress about Adrenal cortex (extracts). 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

Biagini, Christine P. published the artcileInvestigation of the hepatotoxicity profile of chemical entities using Liverbeads and WIF-B9 in vitro models, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is hepatotoxicity chem Liverbeads WIFB9 bioassay.

The cytotoxicity profile of various chem. entities was evaluated using 2 in vitro hepatocyte models. Liverbeads is a cryopreserved model consisting of primary hepatocytes entrapped in alginate beads. WIF-B9 is a hybrid cell line obtained by fusion of rat hepatoma (Fao) and human fibroblasts (WI38). Various reference hepatotoxicants were tested and ranked according to their equivalent concentration 50 (EC50) for various biochem. endpoints (lactate dehydrogenase (LDH) release, 3-(4,5 dimethylthiazol 2yl)-2,5-diphenyl-2H tetrazolium bromure (MTT) activity, ATP (ATP) and glutathione (GSH) levels). The ranking obtained was comparable in both models and consistent with previously published results on hepatocyte monolayers. Ketoconazole, erythromycin estolate, retinoic acid, telithromycin and α-naphthyl-isothiocyanate were among the most toxic chems. in both models, with an EC50 < 200 μM. Troleandomycin, spiramycin, erythromycin, diclofenac, taurodeoxycholate, warfarin, galactosamine, valproic acid and isoniazid were found to be less toxic. Few marked differences, potentially linked to metabolism pathways, were observed between EC50s in the two models for compounds such as cyclosporine A (10 and >831 μM) and warfarin (5904 and 1489 μM) in WIF-B9 and Liverbeads, resp. The results obtained indicate that Liverbeads and WIF-B9 cells are reliable in vitro models to evaluate the hepatotoxic potential of a wide range of chems., irresp. of structure and pharmaceutical class.

Toxicology in Vitro published new progress about Animal cell line (WIF-B9). 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

Zhuang, Shi-Yi published the artcileI2-DMSO Mediated N-H/α-C(sp3)-H Difunctionalization of Tetrahydroisoquinoline: Formal [2 + 2 + 1] Annulation for the Construction of Pyrrolo[2,1-a]isoquinoline Derivatives, SDS of cas: 1468-83-3, the main research area is pyrroloisoquinoline preparation; methyl ketone tetrahydroisoquinoline cascade formal cyclization iodine dimethyl sulfoxide.

An I2-DMSO mediated cascade reaction using Me ketones and 1,2,3,4-tetrahydroisoquinolines (THIQs) as com. available substrates has been developed for construction of pyrrolo[2,1-a]isoquinoline derivatives This metal-free process involves N-H/α-C(sp3)-H difunctionalization of THIQ. Two C-C bonds and one C-N bond are formed in one pot under mild conditions. Besides, a quaternary carbon center has been constructed in this transformation efficiently.

Organic Letters published new progress about Cyclization ([2 + 2 + 1]). 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, SDS of cas: 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Masubuchi, Yasuhiro published the artcileToxicological significance of mechanism-based inactivation of cytochrome P450 enzymes by drugs, Category: benzothiophene, the main research area is review cytochrome terfenadine astemizole griseofulvin tienilic acid dihydralazine.

Cytochrome P 450 (P 450) enzymes oxidize xenobiotics into chem. reactive metabolites or intermediates as well as into stable metabolites. If the reactivity of the product is very high, it binds to a catalytic site or sites of the enzyme itself and inactivates it. This phenomenon is referred to as mechanism-based inactivation. Many clin. important drugs are mechanism-based inactivators that include macrolide antibiotics, calcium channel blockers, and selective serotonin uptake inhibitors, but are not always structurally and pharmacol. related. The inactivation of P450s during drug therapy results in serious drug interactions, since irreversibility of the binding allows enzyme inhibition to be prolonged after elimination of the causal drug. The inhibition of the metabolism of drugs with narrow therapeutic indexes, such as terfenadine and astemizole, leads to toxicities. On the other hand, the fate of P450s after the inactivation and the toxicol. consequences remains to be elucidated, while it has been suggested that P450s modified and degraded are involved in some forms of tissue toxicity. Porphyrinogenic drugs, such as griseofulvin, cause mechanism-based heme inactivation, leading to formation of ferrochelatase-inhibitory N-alkylated protoporphyrins and resulting in porphyria. Involvement of P 450-derived free heme in halothane-induced hepatotoxicity and catalytic iron in cisplatin-induced nephrotoxicity has also been suggested. Autoantibodies against P450s have been found in hepatitis following administration of tienilic acid and dihydralazine. Tienilic acid is activated by and covalently bound to CYP2C9, and the neoantigens thus formed activate immune systems, resulting in the formation of an autoantibody directed against CYP2C9, named anti-liver/kidney microsomal autoantibody type 2, whereas the pathol. role of the autoantibodies in drug-induced hepatitis remains largely unknown.

Critical Reviews in Toxicology published new progress about 5-HT reuptake inhibitors. 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

Verbitskiy, Egor V. published the artcileSynthesis, and structure-activity relationship for C(4) and/or C(5) thienyl substituted pyrimidines, as a new family of antimycobacterial compounds, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is thienyl pyrimidine preparation antimycobacterial agent crystal structure; Antimicobacterial; Cross-coupling; Nucleophilic aromatic substitution of hydrogen; Pyrimidine; Tuberculosis.

Combination of the Suzuki cross-coupling and nucleophilic aromatic substitution of hydrogen (SHN) reactions proved to be a convenient method for the synthesis of C(4) and/or C(5) mono(thienyl) and di(thienyl) substituted pyrimidines from com. available 5-bromopyrimidine. All new pyrimidines are active in micromolar concentrations in vitro against H37Rv, avium, terrae, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The data for acute in vivo toxicity in mice were obtained for these compounds which appear to be promising antitubercular agents.

European Journal of Medicinal Chemistry published new progress about Antimycobacterial agents. 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