Heterocyclic Building Blocks-Benzothiophene

Gibson, T. published the artcileTienilic acid in the treatment of gout and hypertension, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is tienilic acid gout hypertension; health hazard tienilic acid.

Tienilic acid (I) [40180-04-9] (125 mg, twice daily) was given to patients with hypertension and gouty arthritis. In hypertensive patients, the supine and standing diastolic values declined progressively from 101 to 92 and 102 to 94 mm/Hg resp., over a period of 4 wk. There was a significant decrease in serum uric acid and K. I decreased hyperuricemic levels in gouty patients by 50%. Precipitation of acute gout by I probably reflects its profound effect on blood uric acid levels.

Advances in Experimental Medicine and Biology published new progress about Gout. 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

Fehring, Susan I. published the artcileEffect of the glutathione S-transferase inhibitor, tienilic acid, on biliary excretion of sulfobromophthalein, Product Details of C13H8Cl2O4S, the main research area is tienilate interaction sulfobromophthalein biliary excretion; glutathione transferase inhibitor sulfobromophthalein biliary excretion.

Tienilic acid, a phenoxyacetic acid diuretic, reduces the amount of total sulfobromophthalein (BSP) excretion in the isolated perfused rat liver (IPRL). This reduction was primarily by reduction in excretion of conjugated BSP, with excretion of unchanged BSP being relatively unaffected. TA also reduces the amount of conjugated BSP formed in vitro, indicating that its effect in the IPRL may be by means of inhibiting the glutathione S-transferase enzymes involved in the formation of the conjugate. It would appear that a reduction in the biliary excretion of BSP cannot be taken to be an indication of reduced liver function in a general sense.

Chemico-Biological Interactions published new progress about Bile. 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

Zou, Tingting published the artcileFlavour precursor peptide from an enzymatic beef hydrolysate Maillard reaction-II: Mechanism of the synthesis of flavour compounds from a sulphur-containing peptide through a Maillard reaction, Application of 3-Acetylthiophene, the main research area is beef hydrolyzate Maillard reaction product dimethylthiazole isobutylpyrazine.

This study aims to investigate the Maillard reaction products (MRPs) generated between enzymic beef hydrolyzated sulfur-containing oligopeptides and xylose subjected to heat treatment. The priority of the meat aroma contribution is Cys-Gly-Val > GSH > Leu-Cys, whereas Val-Met is relatively Maillard inert. Two peptide-specific aroma compounds, namely, 2-Isobutylpyrazine and 4-butyl-2,5-dimethylthiazole, were produced in a Leu-Cys Maillard reaction system at pH 5.5, showing that the dipeptides with Leu in the N-terminus exhibited high Maillard reactivity. The carbon source and generation pathway of the aroma-active compounds were demonstrated by carbohydrate module labeling (CAMOLA). A new pyrazine generation pathway with xylose-contributed C2 was proposed using this method specifically. Ultra-performance liquid chromatog.-electrospray ionization/quadrupole-time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF MS/MS) was then used to analyze the peptide-specific MRPs to reveal the peptide cleavage, cyclization, and crosslinking with other reactants and intermediates. The main results of this study include that crosslinking between reactants and their intermediates largely occurred in a peptide-specific Maillard reaction; its oligopeptide-specific MRPs were first demonstrated; and the crosslinking products from cyclopeptides and two xyloses and/or their fragments were observed for the first time.

LWT–Food Science and Technology published new progress about Beef. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Application of 3-Acetylthiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Ahokas, J. T. published the artcileInhibition of soluble glutathione S-transferase by diuretic drugs, Formula: C13H8Cl2O4S, the main research area is diuretic liver glutathione transferase inhibition; toxicity diuretic glutathione transferase.

Among several high-ceiling diuretics (bumetanide  [28395-03-1], ethacrynic acid  [58-54-8], furosemide  [54-31-9], indacrynic acid  [56049-88-8], and tienilic acid  [40180-04-9]) only ethacrynic acid was conjugated in vitro to GSH in rat liver cytosol. Ethacrynic, indacrynic, and tienilic acids were all potent inhibitors of glutathione S-aryltransferase  [50812-37-8] in the same preparation; glutathione S-alkyltransferase  [50812-37-8] and glutathione S-epoxide transferase  [50812-37-8] activities were also inhibited by these diuretics, but to a lesser extent. The most potent enzyme inhibitors are related in structure to ethacrynic acid. These observations are discussed with respect to the effect this enzyme inhibition may have on the toxicity of diuretics as well as the toxicity of other coadministered drugs which are also detoxified by the glutathione S-transferase  [50812-37-8] pathway.

Biochemical Pharmacology published new progress about Liver. 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

Dayan, J. published the artcileStudy of the mutagenic activity of 6 hepatotoxic pharmaceutical drugs in the Salmonella typhimurium microsome test, and the HGPRT and sodium-potassium ATPase system in cultured mammalian cells, SDS of cas: 40180-04-9, the main research area is hepatotoxic drug mutagenicity.

Several pharmaceutical drugs show strong hepatotoxicity during therapeutic use: aminophenazone  [58-15-1], clofibrate  [637-07-0], nifuroxazide  [965-52-6], oxamniquine  [21738-42-1], perhexiline maleate  [6724-53-4], and tienilic acid  [40180-04-9]. Their mutagenicity was assessed in the Ames test on 6 strains of S. typhimurium, and in V79 Chinese hamster lung cells with a rat-hepatocyte-mediated metabolic activation system and the hypoxanthine-guanine phosphoribosyl transferase test and the Na+/K+ ATPase assay. Nifuroxazide was pos. in the Ames test in 2 Salmonella strains (TA100 and TA100 Frl). In the hepatocyte-mediated mammalian V79 cell system, nifuroxazide, clofibrate, and aminophenazone were neg. Oxamniquine and tienilic acid were pos. with and without metabolic activation in tests for ouabain and 6-thioguanine resistance. Perhexiline maleate was neg. for the direct induction of 6-thioguanine resistance without metabolic activation, and pos. after metabolization mediated by primary rat hepatocytes. These results suggest the need for some caution in the use of some pharmaceutical drugs because of hepatotoxicity and because 3 out of 6 drugs were shown to be slightly mutagenic in mammalian cells.

Mutation Research, Genetic Toxicology Testing published new progress about Liver. 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

Dansette, P. M. published the artcileHydroxylation and formation of electrophilic metabolites of tienilic acid and its isomer by human liver microsomes: catalysis by a cytochrome P450 IIC different from that responsible for mephenytoin hydroxylation, Related Products of benzothiophene, the main research area is tienilate isomer metabolism liver microsome; cytochrome P450 tienilate isomer metabolism liver.

Tienilic acid (TA; I) is metabolized by human liver microsomes in the presence of NADPH with the major formation of 5-hydroxytienilic acid (5-OHTA) which is derived from the hydroxylation of the thiophene ring of TA. Besides this hydroxylation, TA is oxidized into reactive metabolites which covalently bind to microsomal proteins. Oxidation of an isomer of tienilic acid (TAI) by human liver microsomes, gives a much high level of covalent binding to proteins. Both covalent binding of TA and TAI metabolites are almost completely suppressed in the presence of glutathione. These three activities of human liver microsomes (TA 5-hydroxylation, covalent binding of TA and TAI metabolites) seem dependent on the same cytochrome P 450 of the IIC subfamily, since (i) antibodies against human liver cytochromes P 450 IIC strongly inhibit these three activities, (ii) there is a clear correlation between these activities in various human liver microsomes, and (iii) TA acts as a competitive inhibitor for TAI activation into electrophilic metabolites (Ki ≃ 25 μM) and TAI inhibits TA 5-hydroxylation. However cross inhibition experiments indicate that tienilic acid hydroxylation and mephenytoin hydroxylation, a typical reaction of some human liver P 450 IIC isoenzymes, are not catalyzed by the same member of the P 450 IIC subfamily.

Biochemical Pharmacology published new progress about Liver. 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

Dansette, P. M. published the artcileOxidative activation of the thiophene ring by hepatic enzymes. Hydroxylation and formation of electrophilic metabolites during metabolism of tienilic acid and its isomer by rat liver microsomes, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is thiophene metabolism liver monooxygenase cytochrome; tienilic acid metabolism liver cytochrome P450.

Tienilic acid (TA) is metabolized by liver microsomes from phenobarbital-treated rats in the presence of NADPH with the major formation of 5-hydroxytienilic acid (5-OHTA) which is derived from the regioselective hydroxylation of the thiophene ring of TA. During this in vitro metabolism of TA, reactive electrophilic intermediates which bind irreversibly to microsomal proteins are formed. 5-Hydroxylation of TA and activation of TA to reactive metabolites which covalently bind to proteins required intact microsomes, NADPH and O and are inhibited by metyrapone and SKF 525A, indicating that they are dependent on monooxygenases using cytochromes P 450. Microsomal oxidation of an isomer of TA (TAI) bearing the aroyl substituent on position 3 (instead of 2) of the thiophene ring also leads to reactive intermediates able to bind covalently to microsomal proteins. Covalent binding of TAI, as that of TA, depends on cytochrome P 450-dependent monooxygenases and is almost completely inhibited in the presence of S-containing nucleophiles such as glutathione, cysteine or cyteamine. These results show that 5-OHTA, which has been reported as the major metabolite of TA in vivo in humans, is formed by liver microsomes by a cytochrome P 450-dependent reaction. They also show that 2 thiophene derivatives, TA and TAI, bind to microsomal proteins after in vitro metabolic activation, TAI giving a much higher level of covalent binding than TA (about 5-fold higher) and a much higher covalent binding:stable metabolites ratio (4 instead of 0.5).

Biochemical Pharmacology published new progress about Liver. 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

Ayotte, P. published the artcileFailure of phenobarbital or butanediol pretreatment to potentiate tienilic acid hepatotoxicity in vivo in the rat, Product Details of C13H8Cl2O4S, the main research area is tienilate liver toxicity phenobarbital butanediol.

Tienilic acid  [40180-04-9], a uricosuric diuretic, has been associated with hepatocellular injury in humans as a low-incidence adverse reaction. This phenomenon suggests that a metabolic idiosyncrasy may be involved. The effect of phenobarbital  [50-06-6] and 1,3-butanediol  [107-88-0] pretreatment, prior to tienilic acid challenge (50 or 100 mg/kg, i.v.) on rat hepatic function was studied in vivo. The following parameters were assessed: plasma alanine aminotransferase activity, plasma bilirubin concentration, and bile flow. The results show that neither pretreatment would reveal that tienilic acid possesses hepatotoxic properties in the rat. The discrepancies between these results observed in vivo and those obtained by others in the isolated perfused rat liver suggest: a) that a metabolite formed (under normal conditions) via the phenobarbital- or butanediol-inducible forms of cytochrome P 450  [9035-51-2] is not a likely part of the hepatotoxic sequence of events; b) that the isolated perfused rat liver model in this case is not representative of the in vivo situation.

Archives Internationales de Pharmacodynamie et de Therapie published new progress about Liver. 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

Hildebrandt, E. published the artcileIndirect inhibition of vitamin K epoxide reduction by salicylate, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is salicylate vitamin K epoxide reductase.

Salicylate  [69-72-7] antagonizes the vitamin K  [12001-79-5]-dependent biosynthesis of clotting factors in the rat and produces an elevation of the ratio of vitamin K epoxide  [25486-55-9] to vitamin K in the liver. Vitamin K epoxide is reduced to vitamin k by a vitamin K epoxide reductase  [55963-40-1], and 1 mM salicylate was required to cause a 50% inhibition of the dithiothreitol-dependent in-vitro reduction of vitamin K epoxide by this enzyme. This enzyme was, however, inhibited 50% by as little as 70-80 μM salicylate when reducing equivalent for the reaction were furnished by endogenous cytosolic reductants. This effect on the cytosolic reductant supply was shown to be unrelated to a previously demonstrated inhibition of DT-diaphorase by salicylate. The concentrations of salicylate at which significant inhibitory effects are exerted are in-vitro (50-100 μM) are below the 200 μM levels observed in the livers of rats given an anticoagulating dose of salicylate.

Journal of Pharmacy and Pharmacology published new progress about Liver. 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

Acosta, Daniel published the artcileLack of cytotoxicity of ticrynafen in primary cultures of rat liver cells, HPLC of Formula: 40180-04-9, the main research area is tricrynafen cytotoxicity liver.

Primary cultures of hepatocytes obtained from neonatal Sprague-Dawley rats were grown in arginine-deficient, ornithine-supplemented medium to inhibit fibroblastic overgrowth and to selectively isolate relatively pure cultures of parenchymal hepatocytes. This system of primary hepatocytes was used to study the potential cytotoxicity of ticrynafen (I) [40180-04-9] by measuring cytoplasmic enzyme leakage, cell viability, and total protein per culture dish. Hepatic cultures were treated with the drug in concentrations ranging from 10-3 M to 10-6 M and for durations from 2 to 8 h. The results of the study indicate that ticrynafen was minimally toxic to the hepatocytes.

Toxicology Letters published new progress about Liver. 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