Day: November 17, 2022

Li, Junhao published the artcileEffects of protein flexibility and active site water molecules on the prediction of sites of metabolism for cytochrome P450 2C19 substrates, COA of Formula: C13H8Cl2O4S, the main research area is mol docking protein structure prediction CYP2C19 water metabolism.

Structure-based prediction of sites of metabolism (SOMs) mediated by cytochrome P450s (CYPs) is of great interest in drug discovery and development. However, protein flexibility and active site water mols. remain a challenge for accurate SOM prediction. CYP2C19 is one of the major drug-metabolizing enzymes and has attracted considerable attention because of its polymorphism and capability of metabolizing ∼7% clin. used drugs. In this study, we systematically evaluated the effects of protein flexibility and active site water mols. on SOM prediction for CYP2C19 substrates. Multiple conformational sampling techniques including GOLD flexible residues sampling, mol. dynamics (MD) and tCONCOORD side-chain sampling were adopted for assessing the influence of protein flexibility on SOM prediction. The prediction accuracy could be significantly improved when protein flexibility was considered using the tCONCOORD sampling method, which indicated that the side-chain conformation was important for accurate prediction. However, the inclusion of the crystallog. or MD-derived water mol.(s) does not necessarily improve the prediction accuracy. Finally, a combination of docking results with SMARTCyp was found to be able to increase the SOM prediction accuracy.

Molecular BioSystems published new progress about Dealkylation. 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

Sykes, Matthew J. published the artcilePrediction of Metabolism by Cytochrome P450 2C9: Alignment and Docking Studies of a Validated Database of Substrates, Related Products of benzothiophene, the main research area is cytochrome P450 2C9 substrate docking metabolism.

A validated database of 70 mols. known to undergo biotransformation by CYP2C9 was collated. The mol. alignment program ROCS was used with the query mol. flurbiprofen as a basis for predicting the correct active site orientation of the CYP2C9 database mols. The quality of the results obtained was excellent, with 39 of the first 44 mols. (89%) sorted by ROCS combination score having alignments that accounted for the exptl. observed site of oxidation Transposition of the first 39 correctly aligned mols. into the CYP2C9 active site yielded an average site of metabolism to iron heme distance of 5.21 A, in good agreement with previous exptl. observations. Mol. docking studies were also undertaken, but the results were less successful than the ROCS-based alignment method, indicating that ligand-based approaches with chem. typing are important in the prediction of metabolism by CYP2C9.

Journal of Medicinal Chemistry published new progress about Conformation. 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, Related Products of benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Lechi, A. published the artcileAn evaluation of tienilic acid, a new diuretic uricosuric agent, in the therapy of arterial hypertension, Product Details of C13H8Cl2O4S, the main research area is tienilate hydrochlorothiazide hypertension.

Tienilic acid (I) [40180-04-9] and hydrochlorothiazide (II) [58-93-5] (250 and 50 mg/day, resp.) produced similar decreases in blood pressure and similar changes in plasma or serum electrolytes, urea, creatinine, glucose, cholesterol, and triglycerides and in creatinine clearance in hypertensive patients. I caused a significant decrease in serum uric acid [69-93-2] and an increase in urate clearance, whereas II produced a small increase in serum uric acid but had no effect on urate clearance. Thus, the diuretic and antihypertensive actions of I and II are very similar; the uricosuric/hypouricemic effect of I could assume clin. relevance in long-term therapy of hypertensive patients.

Clinical Science published new progress about Blood plasma. 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

Acharjee, Binkey published the artcileSynthesis, characterization and in vitro evaluation of 3-(4-(methylthio)phenyl)-1-(thiophene-3-yl)prop-2-en-1-one, Product Details of C6H6OS, the main research area is methylthiophenyl thiophenyl propanone chalcone reaction.

In present study, a novel 3-(4-(methylthio)phenyl)-1-(thiophene-3-yl)prop-2-en-1-one (1) was synthesized through the chalcone reaction. The FT-IR, 1H & 13C NMR and mass anal., UV-visible and fluorescent spectroscopic system were utilized to characterize the synthesized compound The charge d. data was used to explain the characteristics of mol. systems. In addition, in the form of the complete and partial d. of states, the HOMO-LUMO energy gap and electrostatic potential map, etc. and some quantum chem. insights have been obtained. Furthermore, to demonstrate the possible applications of thiophene-chalcone derivative (1) in nonlinear optics, the polarizability and first hyperpolarizability were measured. Mol. docking studies were also conducted in order to illustrate the over expression of estrogen receptor in 75% of 5J6A protein. The novel compound was tested for its anticancer and antioxidant activities of in vitro analyses. The substantial antioxidant activity was demonstrated by the newly synthesized compound 1.

Asian Journal of Chemistry published new progress about Antioxidants. 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

Mondal, Arup published the artcileCatalyst-Controlled Regiodivergent C-H Alkynylation of Thiophenes, Synthetic Route of 1468-83-3, the main research area is thiophene regiodivergent alkynylation palladium catalyst; C−H activation; alkynylation; regiodivergent; regioselectivity; thiophenes.

Alkynes are highly attractive motifs in organic synthesis due to their presence in natural products and bioactive mols. as well as their versatility in a plethora of subsequent transformations. A common procedure to insert alkynes into (hetero)arenes, such as the thiophenes studied herein, consists of a halogenation followed by a Sonogashira cross-coupling. The regioselectivity of this approach depends entirely on the halogenation step. Similarly, direct alkynylations of thiophenes were described that follow the same regioselectivity patterns. Herein the authors report the development of a palladium catalyzed C-H activation/alkynylation of thiophenes. The method is applicable to a broad range of thiophene substrates. For 3-substituted substrates where controlling the regioselectivity between the C2 and C5 position is particularly challenging, two sets of reaction conditions enable a regiodivergent reaction, giving access to each regioisomer selectively. Both protocols use the thiophene as limiting reagent and show a broad scope, rendering the authors’ method suitable for late-stage modification.

Angewandte Chemie, International Edition published new progress about Alkynylation. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Synthetic Route of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Pinkert, Tobias published the artcileUse of Strain-Release for the Diastereoselective Construction of Quaternary Carbon Centers, Safety of 3-Acetylthiophene, the main research area is methoxyiminoethyl arene bicyclobutanone ethyl glyoxylate rhodium catalyst three component; hydroxy methoxyiminoethyl arylvinyl succinate preparation diastereoselective.

The formation of quaternary carbon centers with excellent diastereoselectivity via a strain-release protocol were discussed. An organometallic species was generated by Cp*Rh(III)-catalyzed C-H activation, which was then coupled with strained bicyclobutanes (BCBs) and a prochiral carbon electrophile in a three-component reaction. A rare example of BCBs in transition metal catalysis and demonstrates their broad potential to access novel reaction pathways were illustrated. The method developed exhibited a ample functional group tolerance, and the obtained products were further transformed into valuable α-quaternary β-lactones. Preliminary mechanistic investigations suggested a two fold C-C bond cleavage sequence involving σ-bond insertion and an ensuing β-carbon elimination event.

Journal of the American Chemical Society published new progress about Alkenylation. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Safety of 3-Acetylthiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Odlind, Bo published the artcileTubular secretion and effects of tienilic acid in the hen, Product Details of C13H8Cl2O4S, the main research area is tienilic acid kidney tubule secretion.

The relationship between renal tubular secretion of the uricosuric diuretic tienilic acid (I) [40180-04-9] (10 or 30 μg/kg/min) and its saluretic effects was determined in hens using a modified Sperber technique. A true tubular excretion fraction (TTEF) of 29.9% (mean) for tienilic acid was reduced by novobiocin to 3.3%. This demonstrates active tubular secretion of the diuretic by an organic anion transport system in the hen kidney. Infusion of the diuretic into one leg vein caused a marked ipsilateral excess excretion of Cl-, Na+, and K+; these effects were reduced by novobiocin. Thus, in the hen a significant part of the saluretic effect of tienilic acid depends on the active secretion of the drug by tubular cells, as has previously been found for 3 loop diuretics i.e. ethacrynic acid, furosemide and piretanide. Apparently, the saluretic effect of tienilic acid is evoked mainly from the luminal side of the avian nephron. At an infusion rate of 20 μg/kg/min of tienilic acid, a marked saluresis occurred; there was, however, no effect on the urinary urate excretion.

European Journal of Pharmacology published new progress about Kidney tubule. 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

Ramachandran, P. Veeraraghavan published the artcileTiCl4-Catalyzed Hydroboration of Ketones with Ammonia Borane, Formula: C6H6OS, the main research area is secondary alc preparation; ketone titanium chloride ammonia borane hydroboration reduction.

Investigation of a variety of Lewis acids for the hydroboration-hydrolysis (reduction) of ketones with amine-boranes has revealed that catalytic (10 mol %) titanium tetrachloride (TiCl4) in di-Et ether at room temperature immensely accelerates the reaction of ammonia borane. The product alcs. are produced in good to excellent yields within 30 min, even with ketones which typically requires 24 h or longer to reduce under uncatalyzed conditions. Several potentially reactive functionalities are tolerated, and substituted cycloalkanones are reduced diastereoselectively to the thermodn. product. A deuterium labeling study and 11B NMR anal. of the reaction have been performed to verify the proposed hydroboration mechanism.

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

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Mansuy, Daniel published the artcileMolecular structure and hepatotoxicity: compared data about two closely related thiophene compounds, Related Products of benzothiophene, the main research area is review thiophene compound hepatotoxicity metabolism structure; cytochrome P450 thiophene metabolism hepatotoxicity review; tienilic acid isomer hepatotoxicity structure review.

A review with 11 references Two closely related compounds, a diuretic drug tienilic acid (TA) and its isomer TAI have been found to exert very different toxic effects. In human liver microsomes TA is oxidized mainly by CYP 2C9 with formation of a reactive metabolite which covalently binds to CYP 2C9 in a rather specific manner. On the contrary, CYP 2C9-dependent oxidation of TAI leads to reactive metabolite(s) causing an intense covalent binding to several microsomal proteins. Based on these very different behaviors and fates of TA and TAI metabolites, it is proposed that the direct hepatotoxic effects of TAI could be due to an intense, non-specific covalent binding of its reactive metabolite(s) to liver proteins, whereas the toxic effects of the immunoallergic type of TA could be due to the very specific covalent binding of its sulfoxide metabolite to CYP 2C9.

Journal of Hepatology published new progress about Drug toxicity. 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, Related Products of benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Beaune, Philippe H. published the artcileImmunotoxicology of the liver: adverse reactions to drugs, Category: benzothiophene, the main research area is liver immunotoxicol drug adverse reaction review.

A review, with 45 references Liver is a frequent target for drug-induced hepatitis. They can be classified in two categories: the hepatitis in which the drug or a metabolite reach a vital target in the cell and the hepatitis in which the drug triggers an adverse immune response directed against the liver. We will discuss essentially this second kind of disease. They have key clin. features such as the low frequency, the dose independence, the delay between the beginning of drug intake and the triggering of the disease, the shortening of the delay upon rechallenge and very often the presence of autoantibodies in the serum of the patients. Such signs were found in hepatitis triggered by drugs such as halothane, tienilic acid, dihydralazine, anticonvulsants. They will be taken as examples to show the recent progress in the understanding of the mechanisms leading to the disease. It has been postulated that the drug is metabolized into a reactive metabolite binding to the enzyme which generated it; therefore the neoantigen might trigger an immune response characterized by the production of antibodies recognizing the native and or the modified protein. Most of these steps were proven in the cases of halothane, tienilic acid and dihydralazine. Several points seem important in the development of the disease: the equilibrium between toxication and detoxication pathways, the nature and amount of neoantigen, the individual immune response. However, many points remain unclear: for instance, the reason for the very low frequency of this kind of disease; the precise mechanism of the adverse immune response; the risk factors for developing such adverse reactions. Efforts should be made to better understand the mechanisms of this kind of disease: for instance, an animal model, tests to identify drugs at risk for such reactions, the role of these drugs in the processing of P450s and the processing of the neoantigens for their presentation to the immune system.

Journal of Hepatology published new progress about Drug toxicity. 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