Day: November 16, 2022

Preusch, Peter C. published the artcileMechanism of ticrynafen potentiation of coumarin anticoagulant action, HPLC of Formula: 40180-04-9, the main research area is coumarin anticoagulant ticrynafen interaction.

Ticrynafen (I) [40180-04-9] enhanced the degree of hypoprothrombinemia and altered plasma and hepatic vitamin K epoxide  [25486-55-9] concentrations in warfarin (II) [81-81-2]-treated rats. Ticrynafen did not affect vitamin K-dependent carboxylase  [81181-72-8] or vitamin K epoxide reductase  [55963-40-1] activities in vitro. Cytosolic DT-diaphorase  [9032-20-6] was very sensitive to ticrynafen inhibition in vitro, and inhibition of vitamin K  [12001-79-5] reduction via this enzyme is a possible mechanism by which ticrynafen potentiates coumarin anticoagulant action. Inhibition of this enzyme may also contribute to the reported hepatotoxicity of ticrynafen.

Biochemical Pharmacology published new progress about Blood coagulation. 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

Rudik, A. V. published the artcilePrediction of metabolites of epoxidation reaction in MetaToxdol, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is xenobiotics epoxide metabolite epoxidation reaction MetaTox; AUC, area under the ROC curve; Epoxidation; IAP, invariant accuracy of prediction; LMNA, labelled multilevel neighbourhoods of atom; LOO CV, leave-one-out cross-validation; MNA, multilevel neighbourhoods of atom; PASS; SOE, acute toxicity; SOM, site of metabolism; SoLA, structure with one labelled atom; biotransformation; metabolism; prediction; prediction of activity spectra for substances; reactive metabolite; tienilic acid; toxic metabolite; xenobiotics metabolism.

Biotransformation is a process of the chem. modifications which may lead to the reactive metabolites, in particular the epoxides. Epoxide reactive metabolites may cause the toxic effects. The prediction of such metabolites is important for drug development and ecotoxicol. studies. Epoxides are formed by some oxidation reactions, usually catalyzed by cytochromes P 450, and represent a large class of three-membered cyclic ethers. Identification of mols., which may be epoxidized, and indication of the specific location of epoxide functional group (which is called SOE – site of epoxidation) are important for prediction of epoxide metabolites. Datasets from 355 mols. and 615 reactions were created for training and validation. The prediction of SOE is based on a combination of LMNA (Labeled Multilevel Neighborhood of Atom) descriptors and Bayesian-like algorithm implemented in PASS software and MetaTox web-service. The average invariant accuracy of prediction (AUC) calculated in leave-one-out and 20-fold cross-validation procedures is 0.9. Prediction of epoxide formation based on the created SAR model is included as the component of MetaTox web-service (http://www.way2drug.com/mg)..

SAR and QSAR in Environmental Research published new progress about Biotransformation. 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

David, C. published the artcileSubstrate specificity of the luminal sodium-dependent sulfate transport system in the proximal renal tubule as compared to the contraluminal sulfate exchange system, COA of Formula: C13H8Cl2O4S, the main research area is sulfate transporter specificity kidney proximal tubule.

The efflux of [35S]sulfate from the lumen of the proximal renal tubule into tubular cells of rats was measured by the stop-flow tubular-lumen microperfusion technique. The transport parameters obtained and the apparent Ki values of competing substrates were compared with those of the contraluminal influx of [35S]-sulfate from the interstitium into tubular cells. For the luminal (l) sulfate efflux a Km(l, SO42-) of 0.8 mmol/L and a Jmax(l, SO42-) of 0.2 pmol s-1 cm-1 were found. The corresponding contraluminal (cl) values were Km(cl,SO42-) 2.5 mmol/L and Jmax(cl,SO42-) 1.2 pmol s-1 cm-1. Omission of Na+ from the perfusates reduced the luminal efflux of sulfate by 83%, while the contraluminal influx of sulfate was not changed. The most effective inhibitors of both sulfate transport systems are 8-anilino-1-naphthalenesulfonate, orange G, and H2-DIDS. The data indicate that the Na+-dependent luminal and the Na+-independent contraluminal sulfate transport systems accommodate a similar spectrum of anionic substrates, whereby the inhibitory potency against the luminal Na+-dependent sulfate transport system is identical or smaller than against the contraluminal transporter.

Pfluegers Archiv published new progress about Biological efflux. 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, COA of Formula: C13H8Cl2O4S.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Naidek, Naiane published the artcileAnchoring conductive polymeric monomers on single-walled carbon nanotubes: towards covalently linked nanocomposites, Recommanded Product: 3-Acetylthiophene, the main research area is anchoring conductive polymeric monomer walled carbon nanotube covalently nanocomposite.

The functionalization of carbon nanotubes (CNTs) has long been a challenge due to the low reactivity of CNTs. Herein we present a novel approach to covalently functionalize CNTs directly on the carbon surface with three different monomers of conductive polymers. A covalently linked polymeric nanocomposite derived from polypyrrole was also obtained. Highly reactive single-walled carbon nanotube (SWCNT) salts were functionalized with the monomers: 3-bromothiophene, 3-acetylthiophene and 1-(2-bromoethyl)-1H-pyrrole. After the functionalization, a “”grafted from”” approach was used to polymerize the pyrrole-derived SWCNTs and obtain a covalently linked polymeric nanocomposite. All samples were characterized by XPS, thermogravimetric anal., SEM, and IR and Raman spectroscopy. Overall, the results evidence the efficiency of the covalent functionalization directly on the skeleton of the SWCNTs, followed by the polymerization and formation of a novel covalently linked nanocomposite. These materials can benefit future optimal applications such as supercapacitors and artificial muscles.

New Journal of Chemistry published new progress about Artificial muscle. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Recommanded Product: 3-Acetylthiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Matsunaga, Norikazu published the artcileAnalysis of the metabolic pathway of bosentan and of the cytotoxicity of bosentan metabolites based on a quantitative modeling of metabolism and transport in sandwich-cultured human hepatocytes, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is bosentan cytotoxicity metabolism transport hepatocyte.

To quant. understand the events in the human liver, we modeled a hepatic disposition of bosentan and its three known metabolites (Ro 48-5033, Ro 47-8634, and Ro 64-1056) in sandwich cultured human hepatocytes based on the known metabolic pathway. In addition, the hepatotoxicity of Ro 47-8634 and Ro 64-1056 was investigated because bosentan is well known as a hepatotoxic drug. A model illustrating the hepatic disposition of bosentan and its three metabolites suggested the presence of a novel metabolic pathway(s) from the three metabolites. By performing in vitro metabolism studies on human liver microsomes, a novel metabolite (M4) was identified in Ro 47-8634 metabolism, and its structure was determined Moreover, by incorporating the metabolic pathway of Ro 47-8634 to M4 into the model, the hepatic disposition of bosentan and its three metabolites was successfully estimated In hepatocyte toxicity studies, the cell viability of human hepatocytes decreased after exposure to Ro 47-8634, and the observed hepatotoxicity was diminished by pretreatment with tienilic acid (CYP2C9-specific inactivator). Pretreatment with 1-aminobenzotriazole (broad cytochrome P 450 inactivator) also tended to maintain the cell viability. Furthermore, Ro 64-1056 showed hepatotoxicity in a concentration dependent manner. These results suggest that Ro 64-1056 is directly involved in bosentan-induced liver injury partly because CYP2C9 specifically mediates hydroxylation of the t-Bu group of Ro 47-8634. Our findings demonstrate the usefulness of a quant. modeling of hepatic disposition of drugs and metabolites in sandwich cultured hepatocytes. In addition, the newly identified metabolic pathway may be an alternative route that can avoid Ro 64-1056- induced liver injury.

Drug Metabolism & Disposition published new progress about Anxiety disorders. 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, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Ames, Richard P. published the artcileAntihypertensive therapy and the risk of coronary heart disease, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is antihypertensive therapy heart disease health; health hazard antihypertensive.

Diuretic drugs, when used in the treatment of hypertension in patients caused an increase in the serum concentration of total cholesterol and triglycerides. High d. lipoprotein (HDL) cholesterol remains stable with thiazide-type diuretic drugs. Treatment with furosemide  [54-31-9], spironolactone  [52-01-7], reserpine  [50-55-5], and methyldopa  [555-30-6] does not affect serum total cholesterol or triglyceride concentrations However, methyldopa decreases HDL cholesterol, and furosemide increases the ratio of total to HDL cholesterol. When reserpine, methyldopa, or β-blocking drugs are added to diuretic therapy, triglyceride increases and HDL cholesterol decreases. The mechanism of the lipid-lipoprotein alterations is unknown, but the changes correlate with changes in glycoHb and serum glucose noted during diuretic-based therapy. The changes in total cholesterol and HDL cholesterol caused by some antihypertensive agents counterbalance the benefits on the development of coronary heart disease (CHD) expected from the control of blood pressure. Thus, treatment regimens with a more favorable influence on serum lipids may be crucial to better control of CHD. Apparently therapy which does not disturb glucose metabolism is likely to be free of lipid effect, and, therefore, would qualify as preferred therapy for hypertension.

Journal of Cardiovascular Pharmacology published new progress about Antihypertensives. 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, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Roberts, C. J. C. published the artcileComparison of natriuretic, uricosuric, and antihypertensive properties of tienilic acid, bendrofluazide, and spironolactone, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is diuretic tienilate uricosuric antihypertensive; urate blood tienilate diuretic.

In a double-blind cross-over study, 13 previously untreated hypertensive patients were treated orally for 30 days with tienilic acid (I) [40180-04-9], bendrofluazide (II) [73-48-3], or spironolactone (III) [52-01-7], 250, 5, and 100 mg resp.; II caused the greatest natriuresis on the first treatment day, and the most rapid fall in blood pressure. The ultimate antihypertensive effects of I, II, and III were similar. I caused a reduction in serum urate concentrations, and rise in urate clearance, but II and III caused slight urate retention. I and II caused decreases, and III caused an increase in plasma K concentration No untoward effects were observed from I, II, or III. I is thus a moderately potent diuretic which lowers plasma urate concentrations and may be the drug of first choice for hypertensive patients who either already have gout, or are likely to develop it when taking thiazide diuretics.

British Medical Journal published new progress about Antihypertensives. 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

Yonetani, Yukio published the artcileHyperuricemia induced by some antihypertensives and uricosuric drugs in oxonate-treated rats, Application In Synthesis of 40180-04-9, the main research area is antihypertensive uricosuric hyperuricemia pharmacol model.

The effects of antihypertensive and uricosuric drugs were studied on plasma and urinary levels of uric acid [69-93-2] in K oxonate [2207-75-2]-treated rats. Animals with a catheterized aorta were used to successively collect blood samples and this procedure simplified the evaluation of progressive changes of plasma uric acid, under successive loading with K oxonate. The plasma uric acid level of the oxonate-treated rats was increased even with a single administration of diuretic chlorothiazides, furosemide [54-31-9] and diazoxide [364-98-7], and also uricosuric drugs such as tienilic acid [40180-04-9] and probenecid [57-66-9]. A well-maintained plasma uric acid level was also produced by exogenously administered uric acid in rats given allopurinol and K oxonate. Diazoxide, tienilic acid, and probenecid increased the plasma uric acid, whereas diuretic chlorothiazides did not. Furosemide tended to decrease the plasma uric acid level at the early stage of administration in rats treated with allopurinol [315-30-0], oxonate, and uric acid, but increased these levels several hours later when the effect was studied by uric acid loading with rats treated with allopurinol and oxonate. These effects also appeared as changes in the urine-excreted uric acid. Thus, the oxonate-treated rats demonstrated an acutely induced hyperuricemia not only with certain antihypertensives, but also with uricosuric drugs. The utility of these procedures for evaluating the hyperuricemic and uricosuric effects of drugs is discussed.

Japanese Journal of Pharmacology published new progress about Antihypertensives. 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

Cusi, Daniele published the artcileThe effect of tienilic acid on sodium(1+) and potassium(1+) transport in human red cells, HPLC of Formula: 40180-04-9, the main research area is tienilate sodium potassium erythrocyte.

The effect of tienilic acid (I) [40180-04-9] and other antihypertensive drugs with diuretic properties on Na+ and K+ transport in human red cells was investigated. I is a less efficient inhibitor of erythrocyte Na+, K+ cotransport than furosemide [54-31-9], as well as being a weaker diuretic. In addition, the thiazides and K+-sparing diuretics do not inhibit the Na+,K+-cotransport system. Under conditions in which the erythrocytes have all of their saturable Na+ and K+ transport systems blocked, the addition of I increases K+ permeability. This effect shows saturation kinetics with the increase in the internal K+ concentration and could not be blocked by specific inhibitors of K+ channels. Thus, I may affect the opening of transient or permanent K+ channels.

Molecular Pharmacology published new progress about Antihypertensives. 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

Shiradkar, Mahendra Ramesh published the artcileA novel approach to cyclin-dependent kinase 5/p25 inhibitors: A potential treatment for Alzheimer’s disease, Product Details of C13H8Cl2O4S, the main research area is thienyl triazole derivative preparation structure cyclin dependent kinase inhibitor.

Based on the earlier results of the inhouse database and compound library, a series of novel clubbed thienyl triazoles was designed which may emerge as potential cdk5/p25 inhibitors, for the treatment of Alzheimer’s disease. A benign synthesis was planned so as to take an advantage of MAOS (Microwave Assisted Organic Synthesis) method. Evaluation of the SAR of this series has allowed the identification of compounds 4, 5, 7 and 8 from series I while 13, 14, 16 and 17 from series II as significant cdk5/p25 inhibitors and thus have potential as possible treatments for Alzheimer’s disease.

Bioorganic & Medicinal Chemistry published new progress about Alzheimer disease. 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