Category: 40180-04-9

Suleiman, Muhammad R. published the artcileDiscovery of small molecule inhibitors through pharmacophore modeling, molecular docking, molecular dynamics simulation and experimental validation against myeloid cell leukemia-1 (Mcl-1), COA of Formula: C13H8Cl2O4S, the main research area is myeloid cell leukemia inhibitor pharmacophore MD simulation; MM/GBSA; Molecular dynamics simulation; Myeloid cell leukemia-1; virtual screening.

Myeloid cell leukemia-1 (Mcl-1) protein is a family of Bcl-2 (B cell lymphoma 2) rich proteases of the most common increase threshold for genetic aberrations observed in human cancer, including lung, breast, pancreatic, cervical, and ovarian cancers as well as leukemia and lymphoma. Mcl-1 is recognized as an attractive drug target in number of diseases, including cancer. In the present study we surveyed and collected queries compounds from PDB database of Mcl-1 protein and generated pharmacophore-based models adapted to screen the drug-like compounds from FDA approved database. The 206 best lead mols. from pharmacophore-screening were further evaluated by mol. docking, mol. dynamics simulation, MM-GBSA calculation, as well as exptl. validation. Two hits, ZINC00601272 and ZINC00002166, showed the best docking scores, which showed a tendency to inhibit cell viability of HL60 and K562 leukemia cells with Mcl-1 expressions. Conclusively, the present study provides structural information of Mcl-1 inhibitors for next generations of cancer therapeutics through computational and exptl. validation approach.

Journal of Biomolecular Structure and Dynamics published new progress about Antitumor agents. 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

Kobayashi, Kaoru published the artcileCytotoxic effects of benzbromarone and its 1′-hydroxy metabolite in human hepatocarcinoma FLC4 cells cultured on micro-space cell culture plates, Formula: C13H8Cl2O4S, the main research area is benzbromarone hydroxybenzbromarone CYP3A protein glutathione hepatocellular carcinoma anticancer.

Treatment with benzbromarone (BBR), a potent uricosuric drug, can be associated with liver injury. Recently, we reported that culture of human hepatocellular carcinoma FLC-4 cells on micro-space cell culture plates could increase the functional expression of drug-metabolizing enzymes including CYP3A4 and CYP2C9, which are involved in 1′-hydroxylation and 6-hydroxylation of BBR, resp. Therefore, we examined whether BBR and its two metabolites (1′-hydroxy BBR and 6-hydroxy BBR) have cytotoxic effects in FLC4 cells cultured on micro-space cell culture plates. The present study showed that BBR and 1′-hydroxy BBR, but not 6-hydroxy BBR, have cytotoxic effects in cells cultured on micro-space cell culture plates. BBR-induced cytotoxicity was decreased by CYP3A inhibitors (itraconazole and ketoconazole), an Nrf2 activator (tert-butylhydroquinone) and a GSH precursor (N-acetyl-L-cystein). In contrast, BBR-induced cytotoxicity was increased by a GSH biosynthesis inhibitor (buthionine sulfoximine) and an inhibitor of NAD(P)H quinone oxidoreductase 1 (dicoumarol). These results suggested that metabolic activation of 1′-hydroxy BBR via CYP3A, formation of quinone metabolites and the decrease in GSH levels were involved in the BBR-induced cytotoxicity observed in FLC4 cells cultured on micro-space cell culture plates.

Drug Metabolism and Pharmacokinetics published new progress about Antitumor agents. 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, Formula: C13H8Cl2O4S.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Mersch-Sundermann, Volker published the artcileSOS induction in Escherichia coli and Salmonella mutagenicity: a comparison using 330 compounds, SDS of cas: 40180-04-9, the main research area is SOS induction Escherichia Salmonella mutagenicity.

To examine the concordance of two microbial genotoxicity short-term assays, 330 exptl. results for the SOS chromotest using tester strain Escherichia coli PQ37 were compared with the results of the Salmonella/mammalian microsome mutagenicity assay with Salmonella typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and/or TA1538. With respect to qual. features, the concordance between SOS chromotest and Salmonella mutagenicity test results was 86.4% (sensitivity, 78.6%; specificity, 100%; χ2 = 188.6). None of the non-mutagens (N = 120) were able to induce the SOS system. Addnl., 45 of the 210 S. typhimurium mutagens (21.5%) did not induce the SOS repair system. On closer examination, the majority of these 45 compounds (84%) were mutagens with activities between 0.001 and 10 rev/nmol. Even though the exptl. protocols of both systems were not standardized, the correlation coefficient for the exptl. results of the two test systems was 0.7 for the 330 chems. Except for aliphatic epoxides (r = 0.47), the mutagenicity/SOS induction correlations for congeneric data sets (polycyclic aromatic hydrocarbons, nitroarenes, nitroarenofurans, mycotoxins) were even better (r = 0.72-0.95). Addnl., computer automated structure evaluation (CASE) analyses of the nature of the structural determinants associated with each endpoint indicate extensive homologies. The data can be taken to indicate that the two phenomena reflect common mechanisms of action.

Mutagenesis published new progress about Escherichia coli. 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

King, Adam M. published the artcileCapillary ultra performance liquid chromatography-tandem mass spectrometry analysis of tienilic acid metabolites in urine following intravenous administration to the rat, Computed Properties of 40180-04-9, the main research area is capillary UPLC MS tienilate metabolite determination urine pharmacokinetics; Bioanalysis; Capillary UPLC; DMPK; Metabolites; Tienilic acid.

Capillary scale (100 mm × 150 μm id) UPLC/MS/MS, performed using reversed-phase gradient chromatog. on sub 2μm particles, has been successfully employed for the characterization of the metabolites of the drug tienilic acid (TA) excreted via the urine following oral administration to the rat. The capillary LC system provided a significant increase (range ∼11-33-fold) in sensitivity compared with a conventional 150 mm × 2.1 mm id UPLC system. An investigation of the effect of the injection volume and sample mass loading on the capillary column on the results obtained for both endogenous metabolites and TA was performed. This demonstrated that the injection of up to 2μL of rat urine onto the system was permitted while still providing excellent chromatog. results and robustness. Qual. anal. of the urine revealed the presence of TA itself and a total of 15 metabolites of the drug, including those resulting from biotransformations such as hydroxylation or conjugation. The capillary chromatog. system was shown to be robust, and capable of providing comprehensive drug metabolite profiles from small format urine samples such as those obtained from preclin. studies in rodents.

Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences published new progress about Conjugation (bond). 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

Snow, Ina B. published the artcileRenal sites of natriuretic and uricosuric activity of ticrynafen in the mongrel dog, Quality Control of 40180-04-9, the main research area is ticrynafen natriuresis uricosuria mechanism; resorption uric acid sodium ticrynafen.

Following establishment of steady state plasma concentrations of ticrynafen (I) [40180-04-9] in the mongrel dog, the i.v. injection of large doses of p-aminohippurate (PAH) or Na salicylate reduced or blocked the urinary excretion of I. In a similar manner, the i.v. administration of I reduced the urinary excretion of PAH in preloaded dogs. Since PAH and salicylate are actively secreted by a renal tubular organic anion transport system, these data provided evidence for an active tubular secretion of I. The natriuresis and uricosuria from the administration of I to the mongrel dog were reduced by PAH and salicylate at doses which effectively blocked the secretion of I. Apparently, in the dog, the natriuretic and uricosuric activity of I results from the presence of I in the tubular lumen.

Nephron published new progress about Resorption, animal. 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

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

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

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

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

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