Category: benzothiophene

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

Von Kerekjarto, Bela published the artcileThe excretion of 14C-hypoxanthine and its metabolites in rats following administration of uricostatic drugs, Computed Properties of 40180-04-9, the main research area is uricostatic drug efficacy hypoxanthine excretion; allopurinol uricostatic efficacy hypoxanthine; thiopurinol uricostatic efficacy hypoxanthine; tienilate uricostatic efficacy hypoxanthine.

A simple and rapid method to detect the uricostatic activity of hypouricemic drugs is presented. The activity was measured by the rate of excretion of 14C-labeled hypoxanthine  [68-94-0] and its metabolites in rats after administration of uricostatic drugs such as allopurinol  [315-30-0], thiopurinol  [5334-23-6], and tienilic acid  [40180-04-9]. The advantage of the method is the lack of interference by foreign compounds

Advances in Experimental Medicine and Biology published new progress about uricostatic drug efficacy hypoxanthine excretion; allopurinol uricostatic efficacy hypoxanthine; thiopurinol uricostatic efficacy hypoxanthine; tienilate uricostatic efficacy hypoxanthine. 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, Computed Properties of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Neuberger, J published the artcileImmune mechanisms in tienilic acid associated hepatotoxicity., Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is .

In order to investigate the mechanisms underlying the hepatotoxicity associated with tienilic acid (Ticrynafen) ingestion we have looked for evidence of sensitisation to drug altered liver cell determinants using an indirect antibody dependent, cell mediated cytotoxicity assay (ADCC). As targets, hepatocytes were isolated from rabbits pretreated with either tienilic acid or its isomer with or without previous enzyme induction with either phenobarbitone or B-naphthoflavone (BNF). Sera from 16 of 36 patients with presumed tienilic acid hepatotoxicity induced significant cytotoxicity to hepatocytes isolated from rabbits pretreated with BNF and subsequently tienilic acid. Three of 10 sera from patients receiving tienilic acid but without overt liver damage also induced significant cytotoxicity to these hepatocytes, however, although none of 20 normal controls or of 16 patients with other liver diseases did so. Non-organ specific autoantibodies, classified as anti-LKM2, were also detectable. These were present in association with tienilic acid associated antibodies: of the 36 patients with presumed tienilic acid hepatotoxicity, 38% had both antibodies, 18% had only anti-LKM2 antibodies and 9% only tienilic acid associated antibodies. These results suggest that this drug reaction is associated with sensitisation to drug altered liver cell antigens and autoantigens. If ticrynafen associated hepatotoxicity is immune mediated, then one possible mechanism is that the drug induced antigens break tolerance, leading to an immune attack on normal liver cell components.

Gut published new progress in MEDLINE about 40180-04-9, 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

McLain, D A published the artcileAdverse reactions associated with ticrynafen use., Computed Properties of 40180-04-9, the main research area is .

Three hypertensive patients receiving ticrynafen, a new uricosuric diuretic, experienced adverse reactions. One patient experienced acute renal failure, the second experienced a renal stone, and the third had a fatal hemorrhage while receiving anticoagulation therapy with warfarin sodium. All complications can be explained by known actions of the drug and are preventable. However, these reactions illustrate the potential hazards from widespread substitution of ticrynafen for thiazide diuretics in the treatment of hypertension.

JAMA published new progress in MEDLINE about 40180-04-9, 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, Computed Properties of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Kosman, M E published the artcileEvaluation of a new uricosuric diuretic–ticrynafen., Computed Properties of 40180-04-9, the main research area is .

Ticrynafen is an orally administered diuretic that is similar to the thiazides in its therapeutic actions, but unlike the thiazides, it increases urate excretion and lowers serum uric acid levels. Ticrynafen is useful in the treatment of hypertension and in selected cases of chronic congestive heart failure. At present, it appears to be indicated primarily in patients with these disorders who have a history of gout. Patients who are currently receiving a thiazide should not have their therapy arbitrarily changed to ticrynafen because of asymptomatic hyperuricemia.

JAMA published new progress in MEDLINE about 40180-04-9, 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, Computed Properties of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Johnson, M W published the artcileThe risks of asymptomatic hyperuricaemia and the use of uricosuric diuretics., Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is .

Introduction of new uricosuric diuretics will be accompanied by the unknown risk factors associated with the use of any new drug, as demonstrated by reports of hepatic toxicity associated with ticrynafen. In addition to unexpected reactions, there are potential risks related to induction of uricosuria, which are serious and have been reported to occur. More importantly, the risk of developing clinical gout or coronary heart disease due to mild asymptomatic hyperuricaemia appears minimal, so indications for the use of uricosuric diuretics are limited. If a uricosuric diuretic is thought necessary (and is available), it would seem prudent to measure the daily excretion rate of uric acid to identify those patients with hyperuricaemia related to overproduction of uric acid. A uricosuric diuretic should be avoided in those patients, as well as in patients with uric acid stones, and possibly in those with calcium stones. A uricosuric diuretic might be useful for patients with hypertension who also have hyperuricaemia due to a low excretion of uric acid.

Drugs published new progress in MEDLINE about 40180-04-9, 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