Heterocyclic Building Blocks-Benzothiophene

Kerremans, A. L. M. published the artcilePharmacokinetic and pharmacodynamic studies of tienilic acid in healthy volunteers, Category: benzothiophene, the main research area is tienilic acid pharmacokinetics pharmacodynamics.

In 8 healthy adult volunteers the plasma and urinary levels of tienilic acid and its alc. metabolite, and plasma and urinary levels of Na, creatinine  [60-27-5] and uric acid  [69-93-2] were measured after oral administration of tienilic acid (I) [40180-04-9] 250 mg. A high-performance liquid chromatog. method was developed for the determination of I and its metabolite in plasma and urine. The pharmacokinetic parameters differed only slightly from those reported in the literature, as there was faster absorption and a shorter half-life. I was probably excreted by a saturable renal tubular transport mechanism. The pharmacodynamic effects of tienilic acid developed quickly, showing a uricosuric effect and a moderate natriuretic effect. These effects disappeared in about 8 h. An inverse relationship was found between the starting plasma uric acid level in an individual and the maximal uric acid clearance: the higher the plasma uric acid level, the lower was the maximum effect. Correlation between plasma tienilic acid level and natriuretic effect were seen within individuals and intraindividually. Urinary tienilic acid levels and natriuretic effect were also correlated but only intraindividually. No correlation between drug level and uricosuric effect was found.

European Journal of Clinical Pharmacology published new progress about Blood analysis. 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

Vukusic, Ivo published the artcileQuantitative thin-layer chromatographic determination of ticrynafen in canine plasma, SDS of cas: 40180-04-9, the main research area is ticrynafen determination blood; chromatog thin layer ticrynafen blood.

After extraction from plasma with CHCl3, ticrynafen (I) [40180-04-9] was chromatographed on silica-gel K6F thin-layer-chromatog. plates with EtOAc-HOAc (95:5) as the developing solvent. I was determined with a dual-wavelength thin-layer-chromatog. scanner, using 300 nm and 400 nm as the dual wavelengths. The lowest amount of I detectable was 0.1 μg/spot (33 μg/mL), and linear responses were obtained up to 7.5 μg/spot. The relative standard deviations for plasma samples of 3.3-25.0 μg/mL ranged 3.6-13.6%. Recoveries were 75.3% at 3.3 μg/mL and 82.3% at 16.7 μg/mL. The accuracy of the assay was good, the difference between the observed and theor. concentrations for plasma samples of 1.0-7.5 μg/spot being 5.2%. The assay was used to determine I pharmacokinetics in the dog.

Journal of Chromatography, Biomedical Applications published new progress about Blood analysis. 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

Stueber, Wolfgang published the artcileDetermination of ethacrynic and tienilic acid in plasma by gas-liquid chromatography-mass spectrometry, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is ethacrynate tienilate determination blood; gas chromatog ethacrynate tienilate; mass spectrometry ethacrynate tienilate.

ethacrynic acid (I) [58-54-8] and tienilic acid (II) [40180-04-9] were extracted from plasma with (Et)2O. I and II were derivatized with pentafluorobenzyl bromide before being subjected to gas chromatog. on a column packed with 1% OV-17 on Chromosorb W, 80-100 mesh, with He as the carrier gas and the column temperature increasing from 200 to 300° at 30°/min. Using mass spectrometry in the electron-impact mode, detection of the mol. ion peak was possible for both I and II (m/e = 511 and 483, resp.). The recoveries of I and II were 94.5 and 95%, resp. Linear regression of the calibration graph gave a value of 0.998 for 0.5-1μg/mL and the limit of detection was ∼10-20 ng/mL plasma.

Journal of Chromatography, Biomedical Applications published new progress about Blood analysis. 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

Lewis, David F. V. published the artcileOn the estimation of binding affinity (ΔGbind) for human P450 substrates (based on Km and KD values), Synthetic Route of 40180-04-9, the main research area is P450 binding energy method drug substrate QSAR.

A straightforward methodol., based on first principles, for the estimation of human cytochrome P 450-substrate binding energies is outlined, and the system has then been applied successfully to a relatively large dataset of P 450 substrates totaling 90 compounds The results of Quant. Structure-Activity Relationship (QSAR) anal. on the same dataset of cytochrome P 450 (CYP) substrates from the CYP1, CYP2, and CYP3 families, involving a total of 90 compounds, agree favorably with the original anal. based on first principles, thus confirming the use of average values for hydrogen bond and π-π stacking energies, together with utilizing log P values as an estimation of desolvation energies. This method is based on a linear summation of the various contributary factors to the process, including: desolvation, hydrogen bonding, π-π stacking, restricted bond rotation and other energies relating to loss in translational and rotational energy. It is found that, for the majority of P 450 substrates investigated, the first four terms are required for a relatively good estimation (R = 0.98) of the substrate binding affinity (ΔGbind) towards CYP1 and CYP2 enzymes. Consequently, it would appear that the loss in rotational and translational energy, which is thought to occur on substrate binding, apparently has little effect in most cases, possibly due to some degree of residual motion of the enzyme-substrate complex within the endoplasmic reticulum membrane. However, the appearance of a small constant term in the QSAR equation could possibly relate to an average loss in translational and rotational energy for the 90 compounds studied in this investigation.

Current Drug Metabolism published new progress about Binding energy. 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, Synthetic Route of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Mei, Haibo published the artcileIntramolecular Appel Reaction of Trifluoromethylated β-Keto Diazos Enabling Assembly of Trifluoromethylpyrazoles, Recommanded Product: 3-Acetylthiophene, the main research area is trifluoromethylpyrazole preparation; trifluoromethylated keto diazo compound intramol Appel.

A method for the generation of trifluoromethylated β-keto diazos, and their applications in intramol. Appel type reactions was reported for the synthesis of trifluoromethylpyrazoles I [R = Ph, 2-naphthyl, 2-furyl, etc.; R1 = CF3, CF2Cl, C2F5, etc.]. The key success of this reaction was diazo species as an N-nucleophile in Appel reactions. This reaction was conducted under mild conditions and had a broad substrate scope, affording trifluoromethylpyrazoles with up to 94% yields. This protocol represented a new type of Appel reaction and also a new reaction mode of fluoro diazoalkanes.

Organic Letters published new progress about Appel reaction. 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

Xu, Jun published the artcileMulticomponent Bifunctionalization Of Methyl Ketones Enabled By Heterogeneous Catalysis And Solar Photocatalysis In Water, COA of Formula: C6H6OS, the main research area is quinoxalinone derivative green preparation; ketone quinoxalinone tert butyl hypochlorite three component solar photocatalyst.

A novel and green multicomponent transformation for the α-bifunctionalization of Me ketones, quinoxalinones and tBuOCl enabled by heterogeneous catalysis and solar photocatalysis was described to afford quinoxalinone derivatives I [R1 = H, 5-Me, 6-F, etc.; R2 = Me, Bn, 2-FC6H4, et .; R3 = Me, 2-furyl, Ph, etc.]. This reaction was performed in water and under an air atm., afforded the corresponding products I in a moderate-to-good yield.

ACS Sustainable Chemistry & Engineering published new progress about Green chemistry. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, COA of Formula: C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Lopez Garcia, M. Pilar published the artcileHuman liver cytochromes P-450 expressed in yeast as tools for reactive-metabolite formation studies. Oxidative activation of tienilic acid by cytochromes P-450 2C9 and 2C10, SDS of cas: 40180-04-9, the main research area is oxidative activation tienilic acid cytochrome yeast; Saccharomyces cytochrome P 450 tienilic acid.

Human liver cytochromes P 450 (P 450) 2C9 and 2C10 expressed in yeast reproduce all the metabolic features of the oxidation of tienilic acid (2-aryloxo-thiophene) and its isomer (3-aroylthiophene) by human liver microsomes. Microsomes of yeast expressing either P 450 2C9 or P 450 2C10 catalyze (a) the 5-hydroxylation of tienilic acid by NADPH and O2 (Km = 6 μM, Vmax = 2.5 turnover/min), (b) the activation of tienilic acid and its isomer into electrophilic metabolites which covalently bind to proteins, and (c) the formation of a mercaptoethanol adduct which results from the trapping of the tienilic acid isomer sulfoxide by this thiol. Microsomes of yeast expressing human liver P 450 3A4, 1A1 and 1A2 are unable to catalyze these reactions. There is a striking similarity between the quant. characteristics of the oxidation of tienilic acid (and its isomer) by yeast-expressed P 450 2C9 (or 2C10) and by human liver microsomes: (a) analogous Km values (around 10 μM) for tienilic acid 5-hydroxylation, (b) a strong inhibition of tienilic acid oxidation by human sera containing anti-(liver kidney microsomes type 2) (anti-LKM2) antibodies, and (c) almost identical relative ratios of tienilic acid metabolic activation/5-hydroxylation and of tienilic acid activation/the activation of its isomer with both systems. Rates of oxidation of tienilic acid (and its isomer) by yeast microsomes are 6-8-fold higher than those found in human liver microsomes, which would be in agreement with the previously reported amount of P 450 2C9 in human liver. These results not only suggest the important role of P 450 2C9 in the oxidative metabolism of tienilic acid in human liver, but also indicate that the 5-hydroxylation reaction could be a useful marker for P 450 2C9 activity and underline the interest of human liver P 450s expressed in yeast as tools for studying the formation of reactive metabolites.

European Journal of Biochemistry published new progress about Enzyme kinetics. 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

Jean, Pascale published the artcileOxidation of tienilic acid by human yeast-expressed cytochromes P-450 2C8, 2C9, 2C18, and 2C19. Evidence that this drug is a mechanism-based inhibitor specific for cytochrome P-450 2C9, Application In Synthesis of 40180-04-9, the main research area is tienilic acid metabolism liver microsome; cytochrome P450 tienilic acid metabolism.

Oxidation of tienilic acid by human cytochromes P 450 (CYP) 2C9, 2C18, 2C8, and 2C19 was studied using recombinant enzymes expressed in yeast. CYP 2C9 was the best catalyst for 5-hydroxylation of tienilic acid (Km = 5 μM, kcat = 1.7 min ‘), 30-fold more potent in terms of kcat/Km than CYP 2C18 (Km = 150 μM, kcat = 1.8 min ‘) and 300-fold more potent than CYP 2C8 (Km = 145 μM, kcat = 0.2 min-1). CYP 2C19 was unable to catalyze this hydroxylation under our exptl. conditions. A marked effect of the ionic strength on the activities (hydroxylations of tienilic acid and tolbutamide) of these cytochromes P 450 expressed in the yeast strain 334 was observed The effect was particularly great in the case of CYP 2C18, with a tenfold decrease of activity upon increasing ionic strength from 0.02 to 0.1. Specific-covalent binding of tienilic acid metabolites to cytochrome P 450 was markedly higher upon tienilic acid oxidation by CYP 2C9 than by CYP 2C18 and CYP 2C8. Mechanism-based inactivation of cytochrome P 450 during tienilic acid oxidation was observed in the case of CYP 2C9 but was not detectable with CYP 2C18 and CYP 2C8. Tienilic acid thus appears to be a mechanism-based inhibitor specific for CYP 2C9 in human liver. Experiments performed with human liver microsomes confirmed that tienilic acid 5-hydroxylase underwent a time-dependent inactivation during 5-hydroxylation of tienilic acid.

European Journal of Biochemistry published new progress about Enzyme kinetics. 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

Neau, E. published the artcileHydroxylation of the thiophene ring by hepatic monooxygenases. Evidence for 5-hydroxylation of 2-aroylthiophenes as a general metabolic pathway using a simple UV-visible assay, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is tienilic acid hydroxylation liver monooxygenase; thiophene aryl hydroxylation liver monooxygenase.

The 5-hydroxylation of tienilic acid (I) by rat liver microsomes was measured by a new, simple method involving the detection of 5-hydroxytienilic acid (II) by UV-visible spectroscopy. This assay allowed continuous detection of this metabolite and was easily used to determine the kinetic parameters of the reaction (Vmax and Km being resp., 1 nmol product formed/mg protein/min and 14 μM for liver microsomes from phenobarbital-treated rats). This activity was dependent on NADPH and inhibited by CO, SKF 525A and metyrapone, indicating that it is dependent on cytochromes P 450. The UV-visible assay is based on intrinsic properties of 5-hydroxy-2-aroylthiophenes which exist as highly conjugated anions at physiol. pH and exhibit large ε values around 390 nm. Its application to other 2-aroylthiophenes like suprofen, 2-p-chlorobenzoylthiophene and a series of 2-aroylthiophenes with various substituents on the aroyl group showed that, in general, thiophene compounds bearing a 2-arylketo substituent appear to be hydroxylated at position 5 by rat liver microsomes. The kinetic parameters of the 5-hydroxylation of suprofen and 2-p-chlorobenzoylthiophene by liver microsomes from phenobarbital-treated rats were determined and found to be similar to those for I hydroxylation.

Biochemical Pharmacology published new progress about Enzyme kinetics. 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

Kingsley, Laura J. published the artcileCombining Structure- and Ligand-Based Approaches to Improve Site of Metabolism Prediction in CYP2C9 Substrates, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is cytochrome p450 substrate metabolism site prediction QSAR simulation.

Purpose: Predicting atoms in a potential drug compound that are susceptible to oxidation by cytochrome P 450 (CYP) enzymes is of great interest to the pharmaceutical community. We aimed to develop a computational approach combining ligand- and structure-based design principles to accurately predict sites of metabolism (SoMs) in a series of CYP2C9 substrates. Methods: We employed the reactivity model, SMARTCyp, ensemble docking, and pseudo-receptor modeling based on quant. structure-activity relationships (QSAR) to account for influences of both the inherent reactivity of each atom and the phys. structure of the CYP2C9 binding site. Results: We tested ligand-based prediction alone (i.e. SMARTCyp), structure-based prediction alone (i.e. AutoDock Vina docking), the linear combination of the SMARTCYP and docking scores, and finally a pseudo-receptor QSAR model based on the docked compounds in combination with SMARTCyp. We found that by using the latter combined approach we were able to accurately predict 88% and 96% of the true SoMs, within the top-1 and top-2 predictions, resp. Conclusions: We have outlined a novel combination approach for accurately predicting SoMs in CYP2C9 ligands. We believe that this method may be applied to other CYP2C9 ligands as well as to other CYP systems.

Pharmaceutical Research published new progress about Drug metabolism. 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