Day: November 17, 2022

Gershbein, Leon L. published the artcileAction of drugs and chemical agents on rat liver regeneration, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is liver regeneration chem drug; hormone liver regeneration; vaccine liver regeneration.

A large number (> 270) of drugs, chems., and other agents were tested for their effects on the regeneration of liver in hepatectomized rats. Seven anticonvulsants, 4 antiinflammatory drugs, 4 sedatives-hypnotics, the antipyretic-analgesic aminopyrine  [58-15-1], the antifungal griseofulvin  [126-07-8], a uricosuric, a muscle relaxant, a hydrocholeretic, an antihypertensive, and a thyroid inhibitor were hepatotrophic. Most the remaining drugs were inactive in this screening, whereas a few suppressed liver regeneration.

Drug and Chemical Toxicology (1977) published new progress about Analgesics. 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

Sangion, Alessandro published the artcilePBT assessment and prioritization of contaminants of emerging concern: Pharmaceuticals, Application In Synthesis of 40180-04-9, the main research area is persistence bioaccumulation toxicity assessment prioritization contaminant emerging concern pharmaceutical; PBT; Pharmaceuticals; Prioritization; QSAR; Screening.

The strong and widespread use of pharmaceuticals, together with incorrect disposal procedures, has recently made these products contaminants of emerging concern (CEC). Unfortunately, little is known about pharmaceuticals’ environmental behavior and ecotoxicity, so that EMEA (European Medicines Agency) released guidelines for the pharmaceuticals’ environmental risk assessment. In particular, there is a severe lack of information about persistence, bioaccumulation and toxicity (PBT) of the majority of the thousands of substances on the market. Computational tools, like QSAR (Quant. Structure Activity Relationship) models, are the only way to screen large sets of chems. in short time, with the aim of ranking, highlighting and prioritizing the most environmentally hazardous for focusing further exptl. studies. In this work we propose a screening method to assess the potential persistence, bioaccumulation and toxicity of more than 1200 pharmaceutical ingredients, based on the application of two different QSAR models. We applied the Insubria-PBT Index, a MLR (Multiple Linear Regression) QSAR model based on four simple mol. descriptors, implemented in QSARINS software, and able to synthesize the PBT potential in a unique cumulative value and the US-EPA PBT Profiler that assesses the PBT behavior evaluating sep. P, B and T. Particular attention was given to the study of Applicability Domain in order to provide reliable predictions. An agreement of 86% was found between the two models and a priority list of 35 pharmaceuticals, highlighted as potential PBTs by consensus, was proposed for further exptl. validation. Moreover, the results of this computational screening are in agreement with preliminary exptl. data in the literature. This study shows how in silico models can be applied in the hazard assessment to perform preliminary screening and prioritization of chems., and how the identification of the structural features, mainly associated with the potential PBT behavior of the prioritized pharmaceuticals, is particularly relevant to perform the rational a priori design of new, environmentally safer, pharmaceuticals.

Environmental Research published new progress about Analgesics. 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

Chan, Alix I. published the artcileDiscovery of a Covalent Kinase Inhibitor from a DNA-Encoded Small-Molecule Library × Protein Library Selection, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is human kinase MAP2K6 inhibitor DNA encoded small mol library.

We previously reported interaction determination using unpurified proteins (IDUP), a method to selectively amplify DNA sequences encoding ligand:target pairs from a mixture of DNA-linked small mols. and unpurified protein targets in cell lysates. In this study we applied IDUP to libraries of DNA-encoded bioactive compounds and DNA-tagged human kinases to identify ligand:protein binding partners out of 32,096 possible combinations in a single solution-phase library × library experiment The results recapitulated known small mol.:protein interactions and also revealed that ethacrynic acid is a novel ligand and inhibitor of MAP2K6 kinase. Ethacrynic acid inhibits MAP2K6 in part through alkylation of a non-conserved cysteine residue. This work validates the ability of IDUP to discover ligands for proteins of biomedical relevance.

Journal of the American Chemical Society published new progress about Alkylation. 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

Lopez-Garcia, M. Pilar published the artcileThiophene derivatives as new mechanism-based inhibitors of cytochromes P-450: Inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic acid, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is thiophene derivative cytochrome P4502C9 suicide substrate; tienilate metabolite cytochrome P4502C9 suicide substrate; immunoallergic hepatitis tienilate metabolite cytochrome P4502C9.

Oxidation of tienilic acid (TA) by microsomes of yeast expressing two closely related human liver cytochrome P-450s (P 450), P 450 2C9 and 2C10, led to catalysis-dependent loss of activity of these P450s. Under identical conditions, oxidation of a tienilic acid isomer (TAI) failed to give any P 450 inactivation. The loss of P 450 activity during TA oxidation was concomitant with product (5-hydroxytienilic acid, 5-OHTA) formulation, showed pseudo-first-order and saturation kinetics, and was inhibited by an alternative substrate, tolbutamide. Covalent binding of TA metabolites to microsomal proteins occurred in parallel with enzyme inactivation and was partially inhibited by the presence of glutathione in the reaction medium. However, glutathione did not protect P 450 enzyme from inactivation. Thus, TA exhibited all of the characteristics of a mechanism-based inactivator for P 450 2C9 and 2C10 enzymes. The following kinetic parameters were determined in the case of P 450 2C10: t1/2,max = 3.4 min, kinact = 3.6 10-3 s-1, KI = 4.3 μM, kinact/K1 = 813 L mol-1 s-1, and partition ratio = 11.6. Moreover, a specific covalent binding of 0.9 mol of TA metabolite per mol of P 450 2C10 was found to occur before the complete loss of enzyme activity (in incubations performed in the presence of glutathione). A plausible mechanism for P 450 2C10 (2C9) inactivation during TA oxidation is proposed. It involves the intermediate formation of an electrophilic thiophene sulfoxide, which may react at position 5 of its thiophene ring either with H2O to give 5-OHTA or with a nucleophilic group of an amino acid residue of the P 450 active site, which results in its covalent binding to P 450 protein. This alkylation and inactivation of P 450 2C9 (2C10) by TA could be a starting point for the appearance of anti-P 4502C antibodies detected in patients treated with TA and suffering from immunoallergic hepatitis.

Biochemistry published new progress about Alkylation. 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

Wang, Guang-Zu published the artcilePhotocatalytic decarboxylative alkylations of C(sp3)-H and C(sp2)-H bonds enabled by ammonium iodide in amide solvent, Quality Control of 1468-83-3, the main research area is alkylate glycine heteroarene regioselective; aryl glycine heteroarene hydroxyphthalimide redox ester; ammonium iodide salt catalyst decarboxylative alkylation.

A simple ammonium iodide salt in amide solvent catalyzes regioselective decarboxylative alkylation of C(sp3)-H bonds of N-aryl glycine derivatives, of C(sp2)-H bond of heteroarenes, and cascade radical addition to unsaturated bond followed by intramol. addition to arene, with a broad scope of N-hydroxyphthalimide derived redox active esters under visible light irradiation The reactions are suggested to proceed through photoactivation of a transiently assembled chromophore from electron-deficient phthalimide moiety and iodide anion through an anion-π interaction in solvent cage followed by diffusion to generate solvated free radical species to react with C-H substrates. The simplicity, practicality, and broad substrate scope of this method highlight the synthetic power of photocatalysis through transiently assembled chromophore, and will hopefully inspire further developments of low cost photocatalysis based on various non-covalent interactions, which are prevalent in supramol. chem. and biosystems, for sustainable organic synthesis.

Science China: Chemistry published new progress about Alkylation. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Quality Control of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Wang, Shifang published the artcileCopper-Catalyzed Ring-Opening Defluorinative Alkylation of Siloxydifluorocyclopropanes: Synthesis of γ-Fluoro-δ-Ketoesters and γ,δ-Diketonitriles, Category: benzothiophene, the main research area is fluoro ketoester diketonitrile preparation ring opening defluorinative alkylation; copper catalyzed defluorinative alkylation siloxydifluorocyclopropane bromo carboxylic ester amide.

In view of the importance of both fluorinated synthons and homoenolate equivalent, synthetic application of difluorocyclopropanols is desired but remains challenging due to their thermodn. instability. Herein, we use siloxydifluorocyclopropanes as difluorocyclopropanol precursors to carry out new Cu-catalyzed ring-opening defluorinative alkylation. With α-bromo carboxylic esters as coupling partners, the reaction affords γ-fluoro-δ-ketoesters via a CuI/CuII catalytic cycle. Interestingly, by the use of α-bromoamides, the ring-opening defluorinative alkylation is followed by an addnl. intramol. C-N oxidative coupling to deliver a lactam intermediate, which further undergoes defluorination, hydrolysis, ring opening, and dehydration cascade via a CuI/CuII/CuIII catalytic pathway, leading to γ,δ-diketonitriles as the final products.

Journal of Organic Chemistry published new progress about Alkylation. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Category: benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Atallah, Emile published the artcileHydrothermal carbonization of spent mushroom compost waste compared against torrefaction and pyrolysis, Product Details of C6H6OS, the main research area is hydrochar cellulose spent mushroom compost waste hydrothermal carbonization pyrolysis.

The effects of operating conditions (temperature, residence time, and water contents) of hydrothermal carbonization (HTC) of spent mushroom compost (SMC) waste on the hydrochars (HCs) and liquid effluent characteristics were exptl. revised and ranked in increasing order: residence time < dilution factor < temperature HTC upgraded the energy capabilities by doubling their heating values and increasing their fixed carbon contents four times. HTC also enhanced the soil amendment characteristics of SMC feedstock in terms of increasing the adsorption polar heads concentration, enriching its calcium and heavy metals contents after a thorough inorganic contents evaluation, doubling the surface area and increasing the pore size by a factor of five. When compared against biocoal from torrefaction in another study, HCs contained less toxic oxygenated compounds and had an 11% higher HHV at lower temperature (i.e. lower energy cost). On the other hand, HCs showed higher surface area (25 m2/g at 250 °C in HTC compared to 16 m2/g at 550 °C in pyrolysis), close adsorption characteristic, and comparable energy capabilities (22.72 MJ/kg at 700 °Cs in pyrolysis compared to 20.7 MJ/kg at 250 °C in HTC) to pyrolysis at significantly lower temperature GCMS along with UV were used to verify the reviewed degradation mechanism and evaluate the effect of process parameters on this mechanism and on the composition and toxicity of the HTC liquid effluent. They showed that acetic and formic acids, ethanol, phenol, and acetaldehyde were the major compounds that had resulted from the degradation of cellulose, hemicellulose, and lignin. Their concentrations increased with temperature and residence time, but was dependent on temperature in the case of increasing the dilution factor. Nevertheless, HTC degradation enhanced the total acids-phenols concentration in the liquid effluent by 700%. Fuel Processing Technology published new progress about Adsorption. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Product Details of C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Chen, Shixiong published the artcileEffects of C3 -aromatic heterocycles on 1,3,5-triaryl-2-pyrazoline sulfonium salt photoacid generators as light-emitting diode-sensitive cationic photoinitiators, Related Products of benzothiophene, the main research area is aromatic heterocycle triaryl pyrazoline sulfonium salt photoacid cationic photoinitiator.

Four 1,5-diphenyl-3-aromatic heterocyclyl-2-pyrazoline-based sulfonium salt photoacid generators (PAGs) with different aromatic heterocycles substituted on C3 atom and di-Me sulfonium group on C5 atom were synthesized. These PAGs were highly photosensitive in the 365-425 nm light-emitting diode region, and the intramol. charge transfer from the pyrazoline ring to sulfonium salts induced efficient photolysis and high ΦH+. The heterocycles as well as their substituted positions significantly influenced the energy of the S2 orbital, which was determined by the electrochem. and absorption properties of the PAGs. The raising of the S2 orbital energy enlarged the energy gap of S0-S2 and S1-S2, resulting in blue shift of the absorption spectra and increase in the quantum yield of photoacid generation (ΦH+), resp. When the energy of excited electrons was higher than that of the S2 orbital, the transition from S0 to S2 (π-π*) occurred before the C-S cleavage on S1 and the PAGs showed high ΦH+ values (0.52-0.72). The transition from S0 to S1 (π-σ*) occurred when the energy of electrons is lower than that of the S2 orbital, and the PAGs showed low ΦH+ value. The photopolymerization kinetics demonstrated that these PAGs were highly efficient cationic photoinitiators.

Journal of Polymer Science (Hoboken, NJ, United States) published new progress about Absorption. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Related Products of benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Surapaneni, Sekhar published the artcileAbsorption, metabolism, and excretion, in vitro pharmacology, and clinical pharmacokinetics of ozanimod, a novel sphingosine 1-phosphate receptor modulator, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is ozanimod sphingosine phosphate receptor modulator absorption metabolism excretion pharmacol.

Ozanimod is approved for the treatment of relapsing forms of multiple sclerosis. Absorption, metabolism, and excretion of ozanimod were investigated after a single oral dose of 1.0 mg [14C]ozanimod hydrochloride to six healthy subjects. In vitro experiments were conducted to understand the metabolic pathways and enzymes involved in the metabolism of ozanimod and its active metabolites. The total mean recovery of the administered radioactivity was ∼63%, with ∼26% and ∼37% recovered from urine and feces, resp. Based on exposure, the major circulating components were active metabolite CC112273 and inactive metabolite RP101124, which together accounted for 50% of the circulating total radioactivity exposure, whereas ozanimod accounted for 6.7% of the total radioactive exposure. Ozanimod was extensively metabolized, with 14 metabolites identified, including two major active metabolites (CC112273 and CC1084037) and one major inactive metabolite (RP101124) in circulation. Ozanimod is metabolized by three primary pathways, including aldehyde dehydrogenase and alc. dehydrogenase, cytochrome P 450 isoforms 3A4 and 1A1, and reductive metabolism by gut microflora. The primary metabolite RP101075 is further metabolized to form major active metabolite CC112273 by monoamine oxidase B, which further undergoes reduction by carbonyl reductases to form CC1084037 or CYP2C8-mediated oxidation to form RP101509. CC1084037 is oxidized rapidly to form CC112273 by aldo-keto reductase 1C1/1C2 and/or 3β- and 11β-hydroxysteroid dehydrogenase, and this reversible oxidoredn. between two active metabolites favors CC112273. The ozanimod example illustrates the need for conducting timely radiolabeled human absorption, distribution, metabolism, and excretion studies for characterization of disproportionate metabolites and assessment of exposure coverage during drug development.

Drug Metabolism & Disposition published new progress about Absorption. 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

Lewis, David F. V. published the artcileHomology modeling of human cytochromes P450 involved in xenobiotic metabolism and rationalization of substrate selectivity, COA of Formula: C13H8Cl2O4S, the main research area is cytochrome P450 xenobiotic metabolism substrate selectivity.

Mol. modeling of human cytochrome P 450 (CYP) isoforms is described, based on amino acid sequence homol. with a unique bacterial P 450 (CYP102) of known crystal structure. It is found that for the human hepatic P450s involved in the metabolism of xenobiotics, ie. CYP1A2, CYP1A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4, there is a satisfactory agreement between specific substrate characteristics and topog. features of the putative active sites, including complementarity with key amino acid residues in the P 450 hem environments. A combination of homol. model interactions with substrates and certain mol. properties of the compounds themselves provides a methodol. for the evaluation of potential P 450 selectivity in new chem. entities (NCEs).

Experimental and Toxicologic Pathology published new progress about Xenobiotics. 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