Category: 40180-04-9

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

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

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

Shinosaki, Toshihiro published the artcileStop-flow studies on tubular transport of uric acid in rats, Synthetic Route of 40180-04-9, the main research area is kidney tubule urate transport uricosuric.

A stop-flow technique using pyrazinoic acid (PZO)-treated and -untreated rats was devised to evaluate drug effects on bi-directional transport of uric acid in the tubules. Constant venous infusion of test drugs to PZO-untreated rats was used to estimate their inhibitory effects on urate secretion, while their inhibitory effects on urate reabsorption was studied by i.v. administration as a bolus to PZO-treated rats. Probenecid, tienilic acid and R(+)-enantiomer of S-8666, which is the uricosuric component of a new uricosuric diuretic, decreased the (Tua/Pua)/(Tin-Pin) value in the distal and proximal tubules by inhibiting urate secretion in PZO-untreated rats. On the other hand, all of these drugs increased the (Tua/Pua)/(Tin/Pin) value in the tubules in PZO-treated rats, which suggested that they also inhibited the reabsorptive flux of urate. This stop-flow technique in rat kidney showed the possibilities of bi-directional inhibition by these drugs of urate transport in the tubules.

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, Synthetic Route of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Kahela, Paavo published the artcilePolymorphism of tienilic acid, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is polymorphism tienilic acid.

One amorphous and 3 crystalline forms of tienilic acid (I) [40180-04-9] were characterized by using IR spectroscopy and X-ray diffraction. Form A is stable at room temperature, while forms B and C and the amorphous form are metastable. Form B changes to form A near the m.p. and the amorphous form into form C at 120°. Further, during mech. grinding, the mixed form containing forms A and B changes to form A and the amorphous form into form C.

Acta Pharmaceutica Fennica published new progress about polymorphism tienilic acid. 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

Freis, Edward published the artcileComparative effects of ticrynafen and hydrochlorothiazide in the treatment of hypertension, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is ticrynafen hydrochlorothiazide hypertension.

Two dose levels of ticrynafen (I) [40180-04-9], a new uricosuric diuretic, and of hydrochlorothiazide [58-93-5] were randomly assigned double-blind to 240 men with initial diastolic blood pressures in the range of 95 to 114 mm Hg. A dose of 500 mg of I once daily exerted an antihypertensive effect comparable to that of 50 or 100 mg of hydrochlorothiazide. Whereas serum uric acid [69-93-2] levels rose in patients treated with hydrochlorothiazide, they fell markedly in those receiving I. Otherwise, both diuretics produced similar chem. changes in serum. Patients tolerated I as well as they did hydrochlorothiazide over a period of 6 mo of observation, and there was no evidence of serious toxicity or loss of therapeutic effect with I. This antihypertensive agent, in appropriate doses, appears to be as effective and well tolerated as hydrochlorothiazide, and in addition I prevents hyperuricemia.

New England Journal of Medicine published new progress about ticrynafen hydrochlorothiazide hypertension. 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

Guariglia, A. published the artcileMetabolic effects of a natriuretic-uricosuric drug, Ticrynafen, in man, Related Products of benzothiophene, the main research area is Ticrynafen urate sodium potassium metabolism; acid base equilibrium Ticrynafen.

Ticrynafen (I) [40180-04-9] (500 mg) has a maximal diuretic and natriuretic effect in human subjects during the 1st 2 and 3 days after treatment, resp. A significant natriuretic effect was also observed in subjects with reduced glomerular filtration rates. During a period of maximum water and Na+ excretion, the urinary K+ losses were not significant. The urinary K+ losses were only late, after the maximal natriuretic effect. The observed changes in acid-base balance indicated that the development of metabolic acidosis was related to K+ depletion and that it might be prevented by administration of K+-sparing diuretics. Increases in blood and urine uric acid [69-93-2] were observed in all subjects treated with I, including patients with reduced glomerular filteration rates.

International Congress Series published new progress about Ticrynafen urate sodium potassium metabolism; acid base equilibrium Ticrynafen. 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

Mansuy, Daniel published the artcileMetabolic hydroxylation of the thiophene ring: isolation of 5-hydroxytienilic acid as the major urinary metabolite of tienilic acid in man and rat, Application In Synthesis of 40180-04-9, the main research area is tienilate metabolism.

The metabolism of tienilic acid (I) [40180-04-9], a drug containing a thiophene ring, was reinvestigated with man, rat and dog. The major urinary metabolite in man and rat was isolated and completely characterized by comparison with a synthetic compound This metabolite derives from the hydroxylation of the thiophene ring of tienilic acid in position 5. Its isomers, 3-  [90966-20-4] and 4-hydroxytienilic acid  [90966-19-1], were synthesized but could be detected neither in man nor in rat urine. Because of its particular behavior toward electrophiles, 5-hydroxytienilic acid  [90966-18-0] reacted with diazomethane with the formation of a complex mixture of methylated products. This made difficult its measurement by a previously described GLC technique, after acidic extraction and methylation by diazomethane. A new very simple assay using HPLC and direct injection of urine is described in this paper. This assay led to a very precise and reproducible determination of tienilic acid and its hydroxylated metabolite in urine. Up to 50% of tienilic acid is excreted in man or rat urine as 5-hydroxytienilic acid whereas this metabolite does not appear in dog urine. These data describe the first example of metabolic hydroxylation of the thiophene ring.

Biochemical Pharmacology published new progress about tienilate 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

Dubb, J. W. published the artcileTienilic acid: pharmacokinetics, salicylate interaction and creatinine secretion studies, Quality Control of 40180-04-9, the main research area is tienilate pharmacokinetics creatinine salicylate.

Oral doses of 250 mg tienilic acid (I) [40180-04-9] given to normal human volunteers provided peak blood levels of 10-11 μg/mL at 3-4 h after administration. Approx. 40% of the dose was recovered in 24 h, 30% as the parent compound, and 10% as the alc. and diacid metabolites. A 650 mg dose of acetylsalicylic acid [50-78-2] decreased the uricosuric effect of I by inhibiting uric acid secretion. Urine pH decreased with I administration. I inhibited salicylate excretion by either competition for tubular secretion or by increasing passive, pH dependent reabsorption. In normal subjects given a creatinine load, I did not inhibit creatinine [60-27-5] secretion.

Postgraduate Medical Journal, Supplement published new progress about tienilate pharmacokinetics creatinine salicylate. 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

Vinay, Patrick published the artcileMetabolism of tienilic acid (ticrynafen) in man. Pharmacokinetic and mass spectrometric studies, Product Details of C13H8Cl2O4S, the main research area is tienilic acid pharmacokinetics.

The pharmacokinetics and metabolism of tienilic acid (I) [40180-04-9] a new diuretic with uricosuric properties, were studied in human volunteers following single ingestion of 250, 500, or 1000 mg. I was found to be extensively (more than 98%) bound to plasma proteins but not to displace the fraction of urate bound to plasma proteins at the usual therapeutic dosage (250 to 500 mg). The uricosuric and natriuretic effects of I lasted 8-12 h. A peak concentration of 2.5, 4.2 or 10.1 mg/dL was noted in the plasma 2 h following ingestion of each dose. The apparent volume of distribution of the drug was close to that of plasma volume I disappeared rapidly from the plasma according to a first order kinetics and the plasma half-life ranged from 1.6-2.4 h. Gas chromatog. and mass spectrometric studies revealed that 21% of the ingested I is excreted as such in urine over 24 h. Three major metabolites of I were identified in urine: a monohydroxylated I [55901-78-5], a dihydroxylated I [75278-66-9], and a diacid I [66584-08-5]. Including metabolites, 36-47% of the drug was excreted in the urine within 24 h. No significant glucuro- or sulfoconjugation of the drug or its metabolites could be detected in the urine. Excretion of the drug and its metabolites was also noted in the bile. It is concluded that I is rapidly metabolized and excreted in humans with normal kidney and liver function.

European Journal of Drug Metabolism and Pharmacokinetics published new progress about tienilic acid pharmacokinetics. 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