Month: November 2022

Lewis, David F. V. published the artcileQuantitative structure-activity relationships (QSARs) within substrates of human cytochromes P450 involved in drug metabolism, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is QSAR cytochrome P450 substrate drug metabolism free energy.

The results of quant. structure-activity relation (QSAR) analyses are reported for structurally diverse series of chems. which act as substrates or inhibitors for human hepatic microsomal cytochromes P 450 (CYP). In particular, this study focuses on the major catalysts of drug metabolism in man, namely CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. It is found that good correlations (with correlation coefficients ranging from R = 0.94 to 0.99) with P 450 binding affinity (Km and KD) or competitive inhibition (Ki) values are obtained in each case, especially when consideration of hydrogen bonding parameters are included in the QSAR anal., together with the number of π-π stacking interactions.

Drug Metabolism and Drug Interactions published new progress about Free energy of binding. 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

Hutzler, J. Matthew published the artcileMechanism-based inactivation of cytochrome P450 2C9 by tienilic acid and (±)-suprofen: a comparison of kinetics and probe substrate selection, Computed Properties of 40180-04-9, the main research area is tienilic acid suprofen metabolism cytochrome P450 2C9 inactivation.

In vitro experiments were conducted to compare kinact, KI and inactivation efficiency (kintact/KI) of cytochrome P 450 (P 450) 2C9 by tienilic acid and (±)-suprofen using (S)-flurbiprofen, diclofenac, and (S)-warfarin as reporter substrates. Although the inactivation of P 450 2C9 by tienilic acid when (S)-flurbiprofen and diclofenac were used as substrates was similar (efficiency of ∼9 mL/min/μmol), the inactivation kinetics were characterized by a sigmoidal profile. (±)-Suprofen inactivation of (S)-flurbiprofen and diclofenac hydroxylation was also described by a sigmoidal profile, although inactivation was markedly less efficient (∼1 mL/min/μmol). In contrast, inactivation of P 450 2C9-mediated (S)-warfarin 7-hydroxylation by tienilic acid and (±)-suprofen was best fit to a hyperbolic equation, where inactivation efficiency was moderately higher (10 mL/min/μmol) and ∼3-fold higher (3 mL/min/μmol), resp., relative to that of the other probe substrates, which argues for careful consideration of reporter substrate when mechanism-based inactivation of P 450 2C9 is assessed in vitro. Further investigations into the increased inactivation seen with tienilic acid relative to that with (±)-suprofen revealed that tienilic acid is a higher affinity substrate with a spectral binding affinity constant (Ks) of 2 μM and an in vitro half-life of 5 min compared with a Ks of 21 μM and a 50 min in vitro half-life for (±)-suprofen. Lastly, a close analog of tienilic acid with the carboxylate functionality replaced by an oxirane ring was devoid of inactivation properties, which suggests that an ionic binding interaction with a pos. charged residue in the P 450 2C9 active site is critical for recognition and mechanism-based inactivation by these close structural analogs.

Drug Metabolism and Disposition 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, Computed Properties of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Hernandez-Olmos, Victor published the artcileDiscovery of Irbesartan Derivatives as BLT2 Agonists by Virtual Screening, SDS of cas: 40180-04-9, the main research area is irbesartan derivative preparation screening BLT2 leukotriene receptor agonist.

Leuktriene B4 receptor 2 (BLT2) is a G-protein coupled receptor modulation of which is discussed to be a therapeutic option for healing of intestinal lesions. In this work, new BLT2 agonists were identified by a virtual screening of a repurposing library and in vitro assay of the most promising compounds Irbesartan, an approved type-1 angiotensin II receptor (AT1) antagonist, was identified as a moderate BLT2 agonist. An initial SAR study on the irbesartan scaffold was performed resulting in the discovery of a new potent BLT2 agonist (8f, EC50 = 67.6 nM). Irbesartan and 8f were shown to promote proliferation of epithelial colon cells, an effect which was reversible by a BLT2 antagonist.

ACS Medicinal Chemistry Letters published new progress about Angiotensin II receptor type 1 antagonists. 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

Shang, Ya-Fang published the artcileEffect of sugar types on structural and flavor properties of peony seed derived Maillard reaction products, Recommanded Product: 3-Acetylthiophene, the main research area is peony seed derived Maillard reaction product flavor property.

Due to limited utilization of peony seed meal in the food industry, the effect of different sugars on the structural and flavor properties of Maillard reaction products (MRPs) from peony seed meal hydrolyzates (PSH) was investigated. It was noticed that the influence of ribose, xylose, and glucose on the structure of MRPs was greater than maltose and xylooligosaccharide. The MRPs prepared by ribose and xylose showed the greater browning intensity, degree of substitution (DS), and fluorescence intensity. The mol. weight (MW) distribution of 500-1,000 Da, 1,000-3,000 Da, and >3,000 Da was significantly increased in all the MRPs. Partial least squares regression (PLSR) showed that MW distribution, free amino acids, and volatile compounds contributed remarkably to the sensory attributes of MRPs. The sugars that provided the stronger meaty and umami tastes to the MRPs were ribose and xylose. Practical applications : The peony seed meal is accumulated as a main ecol. pollutant during the production of peony seed oil; however, it is an excellent source of plant protein. In the modern food industry, there is an increasing demand for plant proteins over animal derived proteins in various health foods. Therefore, we aimed to prepare flavor agent using peony seed meal protein via Maillard reaction (MR). The effects of sugar types on the color change, structure characteristics, and flavor generation of MRPs were investigated. The improvement of MRPs after the conjugation with various sugar types can increase their industrial potential as flavor enhancers.

Journal of Food Processing and Preservation published new progress about UV absorption. 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

Zhao, Jian published the artcileFormation mechanism of aroma compounds in a glutathione-glucose reaction with fat or oxidized fat, HPLC of Formula: 1468-83-3, the main research area is aroma glutathione glucose fat oxidized flavor; Fat; Formation pathway; Glutathione; Interaction; Lipid degradation; Maillard reaction; Meat flavor; [(13)C(6)]-D-glucose.

Glutathione and glucose with or without chicken fat/oxidized chicken fat were thermally reacted for generation of stewed meat-like aroma, where 42 sulfur-containing odorants were identified by gas chromatog.-mass spectrometry (GC-MS) and gas chromatog.-olfactometry (GC-O). The observed effects or interactions on meat flavor formation due to the fats were similar to previous reports of cysteine-reducing sugar reactions. Carbohydrate module labeling approach demonstrated ten alkyl chain compounds were indeed resulted from the lipid degradation-Maillard reaction interactions, whereas the fats had little effect on formation pathways of compounds only derived from the Maillard reaction. Formation pathways of 26 potent aroma compounds were proposed, particularly, involving two benzene derivatives and seven complex thiophenes. Notably, it was found for the first time just 2-ethylthiophene could result from both an intact skeleton of glucose and the lipid degradation product of 2,4-hexadienal, and the carbohydrate modules methylglyoxal and hydroxyacetone could arise from the glutamic acid of GSH.

Food Chemistry published new progress about Chicken fat Role: BSU (Biological Study, Unclassified), PEP (Physical, Engineering or Chemical Process), BIOL (Biological Study), PROC (Process). 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, HPLC of Formula: 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Lewis, David F. V. published the artcileModeling human cytochromes P450 for evaluating drug metabolism: an update, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is CYP450 drug metabolism mol modeling QSAR.

Cytochrome P 450 (CYP) enzymes represent the major catalysts for the Phase 1 metabolism of drugs and other xenobiotics in Mammalia, including Homo sapiens. There is considerable current interest in evaluating and, consequently, predicting the metabolic fate of new chem. entities (NCEs) via modeling mol. interactions with P 450 constructs, such that sites of metabolism, particular CYP involvement and binding affinities, can be estimated This paper focuses on the principles for homol. modeling of typical enzyme-substrate interactions within the putative active sites of major P450s associated with drug metabolism in man. It also represents an update on previously published work in this journal /1/.

Drug Metabolism and Drug Interactions 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

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