Category: 40180-04-9

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

Lant, A published the artcileDiuretics. Clinical pharmacology and therapeutic use (Part II)., Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is .

25 years have elapsed since the introduction of the first effective oral diuretic, chlorothiazide. Diuretics are now amongst the most widely prescribed drugs in clinical practice worldwide. Availability of these drugs has not only brought therapeutic benefit to countless numbers of patients but it has at the same time provided valuable research tools with which to investigate the functional behaviour of the kidney and other electrolyte-transporting tissues. Despite many remaining gaps in our knowledge of the biochemical processes involved in diuretic drug action, available compounds can be divided into 5 groups on the basis of their preferential effects on different segments of the nephron involved in tubular reabsorption of sodium chloride and water. Firstly, there is a heterogeneous group of chemicals that share the common property of powerful, short-lived diuretic effects that are complete within 4 to 6 hours. These agents act on the thick ascending limb of Henle’s loop and are known as ‘high ceiling’ or ‘loop’ diuretics. The second group are the benzothiadiazines and their many related heterocyclic variants, all of which localise their effects to the early portion of the distal tubule. The third group comprises the potassium-sparing diuretics which act exclusively on the Na+-K+/H+ exchange mechanisms in the late distal tubule and cortical collecting duct. The action of drugs in groups 2 and 3 is prolonged to between 12 and 24 hours. The fourth group consists of diuretics that are chemically related to ethacrynic acid but have the unusual property of combining within the same molecule the property of saluresis and uricosuria. These compounds have actions, to different individual extents, in the proximal tubule, thick ascending limb, and early distal tubule and are known as ‘polyvalent’ diuretics. Finally, there is a mixed group of weak or adjunctive diuretics which includes the vasodilator xanthines such as aminophylline, and the osmotically active compounds such as mannitol. The metabolic consequences of continued diuretic usage are considered along with non-metabolic sequelae such as ototoxicity or interactions with other concurrent treatments. The relationships between the clinical benefits conferred and the potential harms generated by long term diuretic therapy are also discussed.

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

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Matsuda, O published the artcileA case of familial renal hypouricemia associated with increased secretion of para-aminohippurate and idiopathic edema., Computed Properties of 40180-04-9, the main research area is .

A 42-year-old housewife had hypouricemia (serum uric acid ranging from 0.5 to 1.5 mg/dl; 30-89 mumol/l), increased uric acid clearance (47.6-83.0 ml/min), increased maximum tubular secretory capacity for para-aminohippurate, and idiopathic edema. Urate excretion was only minimally suppressed by pyrazinamide, and paradoxically decreased by probenecid. Uric acid clearance did not show any appreciable change after long-term administration of ticrynafen. In response to an increment of extracellular volume by hypertonic saline infusion or long-term 9 alpha-fluorohydrocortisone administration, urate clearance did not show any substantial increase. These data may suggest that not only presecretory but possibly also postsecretory reabsorption of urate is impaired in this patient. No other renal tubular abnormalities were detected. Family study revealed that her renal hypouricemia is hereditary. She was unable to increase urinary excretion of sodium during hypertonic saline infusion and failed to change the response to the sodium-retaining action of 9 alpha-fluorohydrocortisone, presumably accounting for her edema.

Nephron 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

Powers, D published the artcileTicrynafen-induced acute renal failure., HPLC of Formula: 40180-04-9, the main research area is .

Two cases of acute renal failure associated with ticrynafen administration are reported. Both patients had received hydrochlorothiazide prior to the institution of ticrynafen therapy and were mildly hyperuricemic. Flank pain, oliguria, and azotemia developed after the institution of ticrynafen in both cases. Clinical and laboratory features were consistent with acute uric acid nephropathy in both patients. In addition, a newly formed collection of radiolucent material was found by intravenous urography in the renal pelvis of one of the patients. Both patients were treated with intravenous fluids and sodium bicarbonate. One of the patients received allopurinol as well. Complete recovery of renal function was observed in both patients. Ticrynafen-induced hyperuricosuria in these previously volume-depleted and hyperuricemic subjects is felt to have been responsible for intrarenal and extrarenal deposition of uric acid in our patients.

Clinical toxicology 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, HPLC of Formula: 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Hiremath, Chaitanya N. published the artcileAbbreviated Profile of Drugs (APOD): modeling drug safety profiles to prioritize investigational COVID-19 treatments, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is abbreviated profile drug APOD modeling safety profiles prioritize investigational; ADMET; Abbreviated Profile of Drugs (APOD); COVID-19; Drug discovery; Drug safety profile; Pharmacokinetic prediction.

Safe and effective oral formulation of a drug that is easy to store, transport, and administer, is imperative to reach the masses including those without adequate facilities and resources, in order to combat globally transmitted coronavirus disease 2019 (COVID-19). In this decision analytic modeling study, the safety of investigational COVID-19 drugs in clin. trials was assessed using the Abbreviated Profile of Drugs (APOD) methodol. The method was extensively tested for various unbiased datasets based on different criteria such as drugs recalled worldwide for failing to meet safety standards, organ-specific toxicities, cytochrome P 450 inhibitors, and Food and Drug Administration (FDA) approved drugs with remarkable successes. Exptl. validation of the predictions made by APOD were demonstrated by comparison with a progression of multiparametric optimization of a series of cancer drugs that led to a potent drug (GDC-0941) which went into the clin. development. The drugs were classified into three categories of safety profiles: strong, moderate and weak. A total of 3556 drugs available in public databases were examined According to the results, drugs with strong safety profiles included molnupiravir (EIDD-2801), moderate safety profiles included dexamethasone, and weak safety profiles included lopinavir. In this anal., the physicochem.-pharmacokinetic APOD fingerprint was associated with the drug safety profile of withdrawn, approved, as well as drugs in clin. trials and the APOD method facilitated decision-making and prioritization of the investigational treatments.

Heliyon published new progress about COVID-19. 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

Parkinson, Andrew published the artcileAn evaluation of the dilution method for identifying metabolism-dependent inhibitors of cytochrome P450 enzymes, Quality Control of 40180-04-9, the main research area is liver microsome dilution cytochrome P450 inhibitor metabolism.

Metabolism-dependent inhibition (MDI) of cytochrome P 450 is usually assessed in vitro by examining whether the inhibitory potency of a drug candidate increases after a 30-min incubation with human liver microsomes (HLMs). To augment the IC50 shift, many researchers incorporate a dilution step whereby the samples, after being preincubated for 30 min with a high concentration of HLMs (with and without NADPH), are diluted before measuring P 450 activity. In the present study, we show that the greater IC50 shift associated with the dilution method is a consequence of data processing. With the dilution method, IC50 values for direct-acting inhibitors vary with the dilution factor unless they are based on the final (postdilution) inhibitor concentration, whereas the IC50 values for MDIs vary with the dilution factor unless they are based on the initial (predilution) concentration When the latter data are processed on the final inhibitor concentration, as is commonly done, the IC50 values for MDI (shifted IC50 values) decrease by the magnitude of the dilution factor. The lower shifted IC50 values are a consequence of data processing, not enhanced P 450 inactivation. In fact, for many MDIs, increasing the concentration of HLMs actually leads to considerably less P 450 inactivation because of inhibitor depletion and/or binding of the inhibitor to microsomes. A true increase in P 450 inactivation and IC50 shift can be achieved by assessing MDI by a nondilution method and by decreasing the concentration of HLMs. These results have consequences for the conduct of MDI studies and the development of cut-off criteria.

Drug Metabolism and Disposition published new progress about Dilution. 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