Category: 40180-04-9

Beaune, Ph. published the artcileImmunotoxicology and expression of human cytochrome P450 in microorganisms, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is autoimmune hepatitis drug cytochrome P450; microorganism human cytochrome P450 expression.

Drug-induced hepatitis can be caused by an abnormal immunol. response. In the case of tienilic acid- and dihydralazine-induced hepatitis, the authors postulated a scheme in which a P 450 produced a reactive metabolite (step 1); this reactive metabolite bound to the P 450 producing it (step 2) leading to a neoantigen triggering the immune response (step 3); the autoantibodies produced during the immune response recognized the P 450 producing the reactive metabolite (step 4). The use of microorganisms (yeast or bacteria) expressing cloned human P 450 helped in proving some steps of this postulated scheme, particularly steps 1 and 4.

Toxicology published new progress about Autoimmune hepatitis. 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

Garay, R. P. published the artcileThe significance of the relative effects of loop diuretics and anti-brain edema agents on the sodium-potassium-chloride cotransport system and the chloride/NaCO3- anion exchanger, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is biol transport diuretic brain edema.

3-Amino-5-sulfamoylbenzoic acids and several series of (aryloxy)alkanoic acids were evaluated for their inhibitory effects on 2 human erythrocyte ion transport systems – the Na+,K+ cotransport system and the DIDS-sensitive anion carrier. Several classic loop diuretics, including the (aryloxy)alkanoic acid ethacrynic acid  [58-54-8] and several 3-amino-5-sulfamoylbenzoic acids, like bumetanide  [28395-03-1] and furosemide  [54-31-9], displayed relatively strong inhibitory activity vs. the cotransport system with relatively weaker action vs. the anion carrier. Furthermore, diuretic potency correlated with cotransport inhibitory potency. Another class of (aryloxy)alkanoic acids, namely the [(2,3-dihydro-1H-inden-5-yl)oxy]acetic acids, such as indacrinone  [56049-88-8] and MK-473  [53108-00-2], which exhibit less potent loop diuretic activity, were less potent cotransport inhibitors and more effective inhibitors of the anion carrier. Still other (aryloxy)alkanoic acids, with little saliuretic activity, namely a subclass of [(2,3-dihydro-1H-inden-5-yl)oxy]alkanoic acids and a series of [(2,3,9,9a-tetrahydro-1H-fluoren-7-yl)oxy]acetic acids displayed little or no inhibitory action on the cotransport system but enhanced inhibitory action on the anion carrier. The relative anion carrier inhibitory potency correlated well with the relative inhibitory activity of each compound on bicarbonate-stimulated cell swelling in cat cerebrocortical slices.

Naunyn-Schmiedeberg’s Archives of 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, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Roch-Ramel, Francoise published the artcileEffects of uricosuric and antiuricosuric agents on urate transport in human brush-border membrane vesicles, Related Products of benzothiophene, the main research area is urate transport brush border uricosuric antiuricosuric; kidney brush border urate transport uricosuric.

Inhibition of [14C]-urate uptake by uricosuric and antiuricosuric agents was investigated in human brush-border membrane vesicles, urate being transported either by anion exchange mechanisms or by voltage sensitive pathway. The IC50 for drugs on [14C]-urate uptake in vesicles loaded with 1 mM cold urate or with 5 mM lactate was, resp.: 0.7 and 0.3 μM for benzbromarone; 6 and 4 μM for salicylate; 133 and 13 μM for losartan; 520 and 190 μM for sulfinpyrazone and 807 and 150 μM, for probenecid. The IC50 ratio for [14C]-urate uptake in exchange for cold urate or for lactate varied from about 1 for salicylate to 10 for losartan, supporting the hypothesis that two distinct anion exchangers are involved in urate transport. Application of Hill equation revealed that urate/anion exchangers have more than one binding site, possibly two binding sites with high cooperativity, for benzbromarone and sulfinpyrazone, but only one for probenecid, salicylate and losartan. The uricosuric diuretic, tienilic acid was 10 to 50 times more potent than hydrochlorothiazide, chlorothiazide and furosemide, for inhibiting [14C]-urate uptake in exchange for cold urate. This higher potency is the reason of its uricosuric properties. All uricosuric agents, as well as the antiuricosuric agents, pyrazinoate and ethambutol, had a much lower potency for inhibiting [14C]-urate uptake through the voltage sensitive pathway (apical secretory step) than through the urate/anion exchangers. This suggests that antiuricosuria, induced by pyrazinoate and ethambutol, as well as by low concentrations of uricosuric agents, does not result from an inhibition of the apical voltage sensitive pathway.

Journal of Pharmacology and Experimental Therapeutics 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, Related Products of benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Maass, Alfred R. published the artcileRenal pharmacology of tienilic acid, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is tienilic acid pharmacol kidney; diuresis tienilic acid; natriuresis tienilic acid.

Tienilic acid (I) [40180-04-9] (10 mg/kg), administered i.v. to hydrated dogs, caused a moderate natriuresis, an increased osmolal clearance, and a neg. free water clearance, whereas I (15 mg/kg, i.v.) administration to hydropenic dogs caused a natriuresis and a diuresis. I resembled hydrochlorothiazide in the pattern of electrolyte response, the maximum natriuresis obtained, the comparable chloruresis, the modest kaliuresis, the prolonged duration of activity and natriuresis in the alkalotic and acidotic dog but differed from hydrochlorothiazide in being uricosuric in the dog. p-Aminohippurate (PAH) inhibited the renal secretion of I, and I inhibited renal PAH secretion. Apparently, the secretion of I is an active process and the site of the natriuretic activity of I is within the lumen of the renal tubule.

Postgraduate Medical Journal, Supplement 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, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

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

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