Category: 40180-04-9

Stote, R. M. published the artcileTicrynafen: site of natriuretic activity, Product Details of C13H8Cl2O4S, the main research area is ticrynafen diuresis natriuresis mechanism.

In normal subjects given ticrynafen (I) [40180-04-9] 500 and 1000 mg oral doses under conditions of water diuresis, there was a decrease in free water excretion as osmolar clearance increased. During hydropenia, there was no change in free-water reabsorption as osmolar clearance increased. Maximum Na excretion reached 5.2% of the filtered load. At 500 mg doses, there was no effect on phosphate excretion; with 1000 mg doses, there was a reduction in phosphate excretion. During bicarbonate infusion, there was no change in the absolute or percent reabsorption of bicarbonate. After chronic administration of I, there was no impairment of excretion of an acute acid load. Uric acid excretion increased at least 3-fold in all studies. Thus, at 500 and 1000 mg oral doses, I has the characteristics of a diuretic which is active in the cortical diluting segment of the distal nephron.

Nephron published new progress about Diuresis. 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

Dan, Takashi published the artcileMechanism of uricosuric action of AA-193 in DBA/2N mice, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is AA193 uricosuric urate mouse.

Six strains of mice were investigated to find an animal model suitable for researching the mechanism of uricosuric agents. A clearance method and a pyrazinamide suppression test were used to examine the mechanism of urate excretion in the kidney and the mode of action of uricosurics, resp. The neg. correlation between the urinary urate excretion and the endogenous plasma urate level was observed, suggesting the net reabsorption of urate may vary between strains. DBA/2N mice showed the lowest fractional excretion of urate (0.278), and the effects of uricosurics on DBA/2N mice are analogous to those of human. This mouse strain is a useful model for the study of uricosurics. AA-193 (I), a potent new uricosuric agent, was tested in DBA/2N mice and found to have a mode of action different from well-known uricosuric agents. It appeared to inhibit presecretory reabsorption in the proximal tubules.

Journal of Pharmacology and Experimental Therapeutics published new progress about Diuresis. 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

Dan, Takashi published the artcileA selective uricosuric action of AA-193 in rats: comparison with its effect on PAH secretion in vivo and in vitro, Quality Control of 40180-04-9, the main research area is AA193 kidney urate diuresis PAH.

The uricosuric action of AA-193 was compared with the effect on PAH secretion in rats. I.v. administration of AA-193 elevated the fractional excretion of urate (FEu4ate) in a dose-dependent manner at doses 0.1-10 mg/kg. Only at the highest dose caused a momentary decrease in FEPAH. Tienilic acid and probenecid reduced FEPAH at uricosuric EDs. To compare the inhibitory effects of uricosurics on urate reabsorption and PAH secretion more directly, the effects of uricosurics on the OH- gradient-dependent urate uptake were studied in brush-border membrane vesicles and the net PAH accumulation in cortical renal slices. The relation between the affinity of uricosuric drug for urate and PAH transporters corresponded well with the difference between the effects on FEurate and FEPAH. The relative affinity of AA-193 for the urate uptake was 83-fold greater than that for the PAH accumulation. In contrast with other uricosurics, AA-193 has a much higher affinity for urate reabsorption system than for the common pathway of weak organic acids in rats.

Naunyn-Schmiedeberg’s Archives of Pharmacology published new progress about Diuresis. 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

Koechel, Daniel A. published the artcileAcute effects of alkylating agents on canine renal function and ultrastructure: high-dose ethacrynic acid vs. dihydroethacrynic acid and ticrynafen, Category: benzothiophene, the main research area is kidney function ultrastructure ethacrynate derivative.

The renal effects of 2 relatively high doses of ethacrynic acid (EA) [58-54-8] (i.e., 66 and 151 μmol/kg i.v.) and an equivalent high dose (i.e., 151 μmol/kg) of 2 nonalkylating derivatives of EA dihydroethacrynic acid (EA-H2) [5378-94-9] and, ticrynafen  [40180-04-9] were studied in dogs. Both doses of EA produced a profound diuresis of similar magnitude. However, only the larger dose was associated with a concomitant reduction in the glomerular filtration rate, a downward trend in the renal blood flow, a proteinuric response in 4 of the 7 dogs in the treatment group, and a reproducible vacuolation of the initial portion of the proximal convoluted tubules (i.e., the S1 cells). EA-H2 induced a small, transient increase in the excretion rates of Na, Cl, and K, but failed to elicit a proteinuric response or alter proximal tubular ultrastructure. Ticrynafen, a far more efficacious diuretic agent than EA-H2, likewise failed to trigger a proteinuric response or changes in renal ultrastructure. The combination of acidic (anionic) and alkylating properties of EA is thought to be responsible for the proximal tubular effects observed in this study.

Journal of Pharmacology and Experimental Therapeutics published new progress about Diuresis. 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

Minor, Steve published the artcileThe effects of ticrynafen in the rat, Category: benzothiophene, the main research area is ticrynafen diuresis uricosuria.

The i.v. infusion of ticrynafen (I) [40180-04-9] (50 mg/kg/h) in rats had no effect on glomerular filtration rate, but increased the urine flow from 4.4 μL/min/g kidney to 19.2; urinary Na excretion increased from 0.14 μEq/min/g kidney to 2.35 and urate [69-93-2] excretion from 2.8 μg/min/g kidney to 4.0. There was no change in the urinary phosphate excretion. In awake animals, I administration decreased the free water clearance from 6.47 to 3.50, but no change in free water reabsorption was observed Thus, I is a uricosuric and diuretic agent in the rat. The natriuresis appears to derive from an inhibitory action of this agent in the cortical diluting segment of the nephron. In comparison to a related uricosuric diuretic, MK-196, I is less potent with respect to both its uricosuric and diuretic properties in the rat.

Research Communications in Chemical Pathology and Pharmacology published new progress about Diuresis. 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

Ahokas, J. T. published the artcileThe effect of tienilic acid on paracetamol toxicity, Related Products of benzothiophene, the main research area is tienilate paracetamol toxicity glutathione transferase.

Tienilic acid (I) [40180-04-9] inhibited the activity of mouse liver cytosolic glutathione-S-transferase (GSH-t) [50812-37-8] in vitro, with inhibition ranging 23-48%. In mice, the administration of paracetamol (II) [103-90-2] (302 mg/kg, i.p.), a drug normally detoxified through conjugation by the GSH-t system, along with I (40 mg/kg, i.p.) did not result in an increase of II toxicity. Thus, the interaction between II and a strong GSH-t inhibitor, I, does not lead to enhanced II toxicity. Results are discussed with respect to II detoxification via GSH-t.

IRCS Medical Science published new progress about Cytosol. 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

Dan, Takashi published the artcileUricosurics inhibit urate transporter in rat renal brush border membrane vesicles, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is uricosuric urate transporter kidney brush border.

It has been proposed that a urate-anion exchanger system in brush border membrane vesicles (BBMV), which mediates hydroxyl ion (OH-) gradient-dependent urate uptake, is the most likely route for the mediation of urate transport in the first step of urate reabsorption in the proximal tubules. Luminal drugs which inhibit urate reabsorption would inhibit the transport of urate into the cell by blocking the urate-anion exchanger. To confirm this hypothesis, the inhibitory effects of well-known uricosuric drugs on the OH-/urate exchange in BBMV were studied. The rank order of potency was benzbromarone > tienilic acid > sulfinpyrazone > probenecid, which is consistent with clin. doses in man. AA-193 (5-chloro-7,8-dihydro-3-phenylfuro[2,3-g]-1,2-benzisoxazole-7-carboxylic acid), an excellent candidate for a uricosuric, exerted the most potent inhibition on urate uptake (Ki = 0.12 μM). In contrast with that by stilbene disulfonates, the inhibition by AA-193 or benzbromarone was reversible.

European Journal of Pharmacology published new progress about Anions. 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

Ullrich, Karl J. published the artcileContraluminal organic anion and cation transport in the proximal renal tubule: V. Interaction with sulfamoyl- and phenoxy diuretics, and with β-lactam antibiotics, SDS of cas: 40180-04-9, the main research area is kidney tubule contraluminal ion transport; xenobiotic ion transport kidney tubule; antibiotic ion transport kidney tubule; diuretic ion transport kidney tubule.

In order to study the interaction of sulfamoyl- and phenoxy-diuretics as well as of β-lactam antibiotics with the contraluminal anion and cation transport systems, the inhibitory potency of these substances against the influx of [3H]p-aminohippurate, [14C]succinate, [35S]sulfate, and [3H]N1-methylnicotinamide into cortical tubular cells were determined The results show that the probenecid, the diuretics furosemide, piretanide, hydrochlorothiazide, acetazolamide, ethacrynic, and tielinic acid, and the β-lactam antibiotics of the penicillin and cephalosporin type interact with the anion and cation transport systems in a predictable fashion.

Kidney International published new progress about Anions. 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

Lemieux, G. published the artcileThe renal handling of tienilic acid (ticrynafen), a new diuretic with uricosuric properties, HPLC of Formula: 40180-04-9, the main research area is tienilic acid diuresis kidney; ticrynafen diuresis mechanism.

Tienilic acid (I) [40180-04-9] was highly bound to plasma proteins of dogs at 37° (>95% at drug concentrations of 3.0-20.0 mg/dL). Thus, glomerular filtration of the drug is negligible and I must reach the kidney at the antiluminal site of the tubule. During free-flow studies, the clearance of I at stable plasma concentrations (3.0-20.0 mg/dL) ranged from 11-22% of glomerular filtration. These values are 3-5 times greater than that accounted for by filtration of the drug alone and are highly suggestive of tubular secretion. Secretion becomes more apparent during alkalinization of the urine when the clearance of I may rise to 40 and even 100% of glomerular filtration. During stop-flow studies, the urine over plasma ratio of the drug (U/P TA) over that of creatinine (U/P Cr) decreased along the nephron indicating progressive reabsorption. At equivalent plasma concentration, I markedly depressed p-aminohippuric acid (PHA) transport in the proximal tubule. When plasma I concentration was kept low (5 mg/dL) and PAH concentration was raised to 30 mg/dL, the (U/P TA)/(U/P Cr) dropped by 50%. These results indicate active secretion of I in the proximal tubule followed by passive pH dependent reabsorption along the nephron. The drug is transported through the common organic acid pathway by a carrier having higher affinity for I than for PAH.

Nephron published new progress about Kidney. 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

Oker-Blom, Christian published the artcileToxicological studies on tienilic acid in rats, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is tienilic acid toxicity; sex tienilic acid toxicity.

The subacute oral toxicity of tienilic acid (I) [40180-04-9] in male and female rats was studied. Animals were given 0, 30, 120, and 480 mg I/kg as a 3% gum arabic suspension for 28 days. At 30 mg I/kg, blood pressure and serum uric acid [69-93-2] decreased. At the 2 higher dose levels, a slight decrease in Hb and an increase in serum glutamic-pyruvic transaminase [9000-86-6] activity was noticed, and there was a significant increase in the liver weight and serum Mg concentration of male rats, while the liver weight of female rats increased only slightly. One microscopic examination, unicellular necrosis of small groups of liver cells was noted, together with focal round-cell infiltration and some stasis of the 2 higher dose levels in some animals. I had no noticeable effects on other organs or parameters.

Toxicology Letters published new progress about Blood. 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