Day: November 10, 2022

Liu, Ruifeng published the artcile2D SMARTCyp Reactivity-Based Site of Metabolism Prediction for Major Drug-Metabolizing Cytochrome P450 Enzymes, Formula: C13H8Cl2O4S, the main research area is SMARTCyp cytochrome P450 3A4 2D6 2C9 2C19 1A2 human.

Cytochrome P 450 (CYP) 3A4, 2D6, 2C9, 2C19, and 1A2 are the most important drug-metabolizing enzymes in the human liver. Knowledge of which parts of a drug mol. are subject to metabolic reactions catalyzed by these enzymes is crucial for rational drug design to mitigate ADME/toxicity issues. SMARTCyp, a recently developed 2D ligand structure-based method, is able to predict site-specific metabolic reactivity of CYP3A4 and CYP2D6 substrates with an accuracy that rivals the best and more computationally demanding 3D structure-based methods. In this article, the SMARTCyp approach was extended to predict the metabolic hotspots for CYP2C9, CYP2C19, and CYP1A2 substrates. This was accomplished by taking into account the impact of a key substrate-receptor recognition feature of each enzyme as a correction term to the SMARTCyp reactivity. The corrected reactivity was then used to rank order the likely sites of CYP-mediated metabolic reactions. For 60 CYP1A2 substrates, the observed major sites of CYP1A2 catalyzed metabolic reactions were among the top-ranked 1, 2, and 3 positions in 67%, 80%, and 83% of the cases, resp. The results were similar to those obtained by MetaSite and the reactivity + docking approach. For 70 CYP2C9 substrates, the observed sites of CYP2C9 metabolism were among the top-ranked 1, 2, and 3 positions in 66%, 86%, and 87% of the cases, resp. These results were better than the corresponding results of StarDrop version 5.0, which were 61%, 73%, and 77%, resp. For 36 compounds metabolized by CYP2C19, the observed sites of metabolism were found to be among the top-ranked 1, 2, and 3 sites in 78%, 89%, and 94% of the cases, resp. The computational procedure was implemented as an extension to the program SMARTCyp 2.0. With the extension, the program can now predict the site of metabolism for all five major drug-metabolizing enzymes with an accuracy similar to or better than that achieved by the best 3D structure-based methods. Both the Java source code and the binary executable of the program are freely available to interested users.

Journal of Chemical Information and Modeling published new progress about Algorithm (SMARTCyp, 2D ligand structure-based method). 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

Yu, Rongrong published the artcileHighly Enantioselective Nickel-Catalyzed Hydrocyanation of Disubstituted Methylenecyclopropanes Enabled by TADDOL-based Diphosphite Ligands, Application In Synthesis of 1468-83-3, the main research area is nickel catalyzed enantioselective hydrocyanation methylenecyclopropane TADDOL phosphite.

A vast range of novel TADDOL-based diphosphite ligands were first synthesized and applied in the nickel-catalyzed asym. hydrocyanation of disubstituted methylenecyclopropanes. By employing these new catalysts, the conversion of diverse methylenecyclopropanes into their corresponding allylic nitriles was first enabled, in good yield with excellent enantioselectivities.

Organic Letters published new progress about Cyclopropanes Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation) (methylenecyclopropanes). 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Application In Synthesis of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Petersen, Karina published the artcileToxicity of organic compounds from unresolved complex mixtures (UCMs) to primary fish hepatocytes, HPLC of Formula: 19156-54-8, the main research area is Oncorhynchus hepatocyte toxicity unresolved complex mixture; AhR agonist; Cytotoxicity; ER agonist; EROD; Naphthenic acids; Vitellogenin; Xenoestrogen; in vitro.

In the present study, several chems. with structures typical of those found in some UCMs, were assessed for their potential to disrupt membrane integrity, inhibit metabolic activity, activate the aryl hydrocarbon receptor (AhR), and activate the estrogen receptor (ER) in primary rainbow trout hepatocytes (Oncorhynchus mykiss). These endpoints were determined in order to screen for common toxic modes of action (MoA) in this diverse group of chems. EC50 values for cytotoxicity were obtained for 16 compounds and ranged from 77μM-24 mM, whereof aliphatic monocyclic acids, monoarom. acids, polycyclic monoarom. acids and alkylnaphthalenes were the most toxic. The observed cytotoxicity of the chems. correlated well with the hydrophobicity (LogKOW) suggesting that the toxicity was predominantly due to a non-specific MoA. Interestingly, two compounds induced the ER-mediated production of vitellogenin (Vtg) and six compounds induced the AhR-mediated Ethoxyresorufin-O-deethylase (EROD) enzymic activity to >20% of the pos. control; by doing so suggesting that they may act as ER or AhR agonists in fish. The heterogeneous group of ‘UCM compounds’ tested exhibited multiple MoA that may potentially cause adverse effects in fish. Addnl. studies to determine if these compounds may cause adverse effects in vivo at environmentally relevant concentrations, are warranted to identify if such compounds are indeed of potential environmental concern.

Aquatic Toxicology published new progress about Canned fish, rainbow trout. 19156-54-8 belongs to class benzothiophene, name is 4,5,6,7-Tetrahydrobenzo[b]thiophene-3-carboxylic acid, and the molecular formula is C9H10O2S, HPLC of Formula: 19156-54-8.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Nettles, James H. published the artcileFlexible three-dimensional pharmacophores as descriptors of dynamic biological space, COA of Formula: C13H8Cl2O4S, the main research area is flexibility three dimensional pharmacophore fuzzy pattern Algorithm modeling docking.

Development of a pharmacophore hypothesis related to small-mol. activity is pivotal to chem. optimization of a series, since it defines features beneficial or detrimental to activity. Although crystal structures may provide detailed three-dimensional interaction information for one mol. with its receptor, docking a different ligand to that model often leads to unreliable results due to protein flexibility. Graham Richards’ laboratory was one of the first groups to utilize “”fuzzy”” pattern recognition algorithms taken from the field of image processing to solve problems in protein modeling. Thus, descriptor “”fuzziness”” was partly able to emulate conformational flexibility of the target while simultaneously enhancing the speed of the search. In this work, we extend these developments to a ligand-based method for describing and aligning mols. in flexible chem. space termed FEature POint PharmacophoreS (FEPOPS), which allows exploration of dynamic biol. space. We develop a novel, combinatorial algorithm for mol. comparisons and evaluate it using the WOMBAT dataset. The new approach shows superior retrospective virtual screening performance than earlier shape-based or charge-based algorithms. Addnl., we use target prediction to evaluate how FEPOPS alignments match the mols. biol. activity by identifying the atoms and features that make the key contributions to overall chem. similarity. Overall, we find that FEPOPS are sufficiently fuzzy and flexible to find not only new ligand scaffolds, but also challenging mols. that occupy different conformational states of dynamic biol. space as from induced fits.

Journal of Molecular Graphics & Modelling published new progress about 5-HT2C receptors Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study). 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

Feng, Minghao published the artcileDeployment of Sulfinimines in Charge-Accelerated Sulfonium Rearrangement Enables a Surrogate Asymmetric Mannich Reaction, Recommanded Product: 3-Acetylthiophene, the main research area is polysubstituted amino amide preparation chemoselective diastereoselective enantioselective; carboxamide sulfinimine Mannich reaction.

β-Amino acid derivatives are key structural elements in synthetic and biol. chem. Despite being a hallmark method for their preparation, the direct Mannich reaction encounters significant challenges when carboxylic acid derivatives are employed. Indeed, not only is chemoselective enolate formation a pitfall (particularly with carboxamides), but most importantly the inability to reliably access α-tertiary amines through an enolate/ketimine coupling is an unsolved problem of this century-old reaction. Herein, authors report a strategy enabling the first direct coupling of carboxamides with ketimines for the diastereo- and enantioselective synthesis of β-amino amides. This conceptually novel approach hinges on the innovative deployment of enantiopure sulfinimines in sulfonium rearrangements, and at once solves the problems of chemoselectivity, reactivity, and (relative and absolute) stereoselectivity of the Mannich process. In-depth computational studies explain the observed, unexpected (dia)stereoselectivity and showcase the key role of intramol. interactions, including London dispersion, for the accurate description of the reaction mechanism.

Journal of the American Chemical Society published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 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

Burckhardt, Birgitta Christina published the artcileElectrophysiologic characterization of an organic anion transporter cloned from winter flounder kidney (fROAT), Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is flounder kidney anion transporter; sequence Pseudopleuronectes anion transporter.

The 2-electrode voltage clamp technique was used to demonstrate translocation of p-aminohippurate (PAH) and related compounds such as loop diuretics in Xenopus laevis oocytes expressing the renal organic anion transporter from winter flounder kidney (fROAT). In fROAT-expressing oocytes, PAH (0.1 mM) induced a depolarization of 4.2 mV and at a holding potential of -60 mV an inward current of -22.6 nA. PAH-induced current and the current calculated from [3H]PAH uptake were of similar magnitude. Depolarization, inward current, and current-to-uptake relation indicated exchange of the monovalent PAH with a divalent anion, possibly α-ketoglutarate (α-KG), causing net efflux of 1 neg. charge. The kinetic anal. of PAH-induced currents revealed that translocation is dependent on membrane potential, saturable with an apparent Km of 58 μM, and sensitive to probenecid and furosemide. In contrast to probenecid and furosemide, the loop diuretics bumetanide, ethacrynic acid, and tienilic acid and the nephrotoxic mycotoxin ochratoxin A elicited inward currents indicating translocation through fROAT. Substrate-dependent currents provide a tool to elucidate the structure/function relationship of the renal organic anion transporter.

Journal of the American Society of Nephrology published new progress about Anion transporters Role: BAC (Biological Activity or Effector, Except Adverse), BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study). 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

Chen, Nancy published the artcileIn vitro drug-drug interactions of budesonide: inhibition and induction of transporters and cytochrome P450 enzymes, Quality Control of 40180-04-9, the main research area is budesonide drug interaction transporter cytochrome enzyme inhibition; Budesonide; cytochrome P450 enzymes; drug metabolism; drug transporters; drug–drug interactions; glucocorticoid; human hepatocytes; human liver microsomes.

1. Budesonide is a glucocorticoid used in the treatment of several respiratory and gastrointestinal inflammatory diseases. Glucocorticoids have been demonstrated to induce cytochrome P 450 (CYP) 3A and the efflux transporter P-glycoprotein (P-gp). This study aimed to evaluate the potential of budesonide to act as a perpetrator or a victim of transporter- or CYP-mediated drug-drug interactions (DDIs).2. In vitro studies were conducted for P-gp, breast cancer resistance protein and organic anion and cation transporters (OATP1B1, OATP1B3, OAT1, OAT3, OCT2) in transporter-transfected cells. Changes in mRNA expression in human hepatocytes and enzyme activity in human liver microsomes by budesonide were determined for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A.3. The data indicated that budesonide is a substrate of P-gp but is not a substrate or an inhibitor of the other transporters investigated. Budesonide is neither an inducer nor an inhibitor of major CYP enzymes. The effect of P-gp on budesonide disposition is anticipated to be low owing to CYP3A-mediated clearance.4. Collectively, our data indicate there is a low risk of budesonide perpetrating clin. DDIs mediated by the transporters or CYPs studied.

Xenobiotica published new progress about Cation transporters Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Gong, Fei-Yuan published the artcileRhodium-Catalyzed Decarboxylative Hydroacylation of Vinylethylene Carbonates for Regioselective Ester Synthesis, Name: 3-Acetylthiophene, the main research area is salicylaldehyde aryl vinylethylene carbonate rhodium catalyst decarboxylative hydroacylation; aryl butenyl hydroxybenzoate preparation regioselective diastereoselective.

A rhodium(I)-catalyzed decarboxylative hydroacylation of readily available vinylethylene carbonates with salicylaldehydes for regioselective preparation of esters was developed. Reaction optimization revealed that methacrylamide might promote the hydroacylation by bidentate chelation assistance to the cationic rhodium. Mechanistic findings suggested that this one-pot coupling reaction proceeds via Markovnikov hydrorhodation-initiated site-selective β-C-O bond cleavage with concurrent release of CO2.

Advanced Synthesis & Catalysis published new progress about Aromatic esters Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Name: 3-Acetylthiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Shen, Cong published the artcileAccess to axially chiral aryl 1,3-dienes by transient group directed asymmetric C-H alkenylations, Category: benzothiophene, the main research area is axially chiral aryl diene preparation; styrene olefin palladium catalyst asym CH alkenylation.

Herein presented, a Pd-catalyzed atroposelective preparation of aryl 1,3-dienes from readily available styrenes and olefins through an aldehyde derived transient chiral auxiliary, proceeding by enantioselective olefinic C-H alkenylation of styrenes via seven-membered endo-cyclometallation. The generality of the protocol was demonstrated by the smooth conversion of a wide range of 2-vinyl benzaldehyde derivatives to afford up to 99% yields and high to excellent enantioselectivities (up to >99% ee). The derived axially chiral carboxylic acid was demonstrated to be a more efficient ligand in the Cp*Co(III)-catalyzed asym. C(sp3)-H alkylation.

Organic Chemistry Frontiers published new progress about Alkenes Role: PRP (Properties), RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 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

Huang, Mouxin published the artcileDeracemization through photochemical E/Z isomerization of enamines, Recommanded Product: 3-Acetylthiophene, the main research area is aldehyde enamine deracemization; photosensitizer aminocatalyst isomerization.

Catalytic deracemization of α-branched aldehydes is a direct strategy to construct enantiopure α-tertiary carbonyls, which are essential to pharmaceutical applications. Here, authors report a photochem. E/Z isomerization strategy for the deracemization of α-branched aldehydes by using simple aminocatalysts and readily available photosensitizers. A variety of racemic α-branched aldehydes could be directly transformed into either enantiomer with high selectivity. Rapid photodynamic E/Z isomerization and highly stereospecific iminium/enamine tautomerization are two key factors that underlie the enantioenrichment. This study presents a distinctive photochem. E/Z isomerization strategy for externally tuning enamine catalysis.

Science (Washington, DC, United States) published new progress about Diastereoselective synthesis. 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