Category: benzothiophene

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

Marko, Jason A. published the artcileElectrochemical benzylic oxidation of C-H bonds, HPLC of Formula: 1468-83-3, the main research area is electrochem benzylic oxidation carbon hydrogen bond.

Oxidized products have become increasingly valuable as building blocks for a wide variety of different processes and fine chem., especially in the benzylic position. The authors report herein a sustainable protocol for this transformation through C-H functionalization and was performed using electrochem. as the main power source and tert-Bu hydroperoxide as the radical source for the C-H abstraction. The temperature conditions reported here do not increase >50° and use an aqueous-based medium. A broad substrate scope is explored, along with bioactive mols., to give comparable and increased product yields when compared to prior reported literature without the use of electrochem.

Chemical Communications (Cambridge, United Kingdom) published new progress about C-H bond. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, HPLC of Formula: 1468-83-3.

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

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