Shin, Young G.’s team published research in Combinatorial Chemistry & High Throughput Screening in 2011-11-30 | CAS: 40180-04-9

Combinatorial Chemistry & High Throughput Screening published new progress about Computer program (MetaSite). 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, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Shin, Young G. published the artcileComparison of metabolic soft spot predictions of CYP3A4, CYP2C9 and CYP2D6 substrates using MetaSite and StarDrop, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is site of metabolism CYP3A4 CYP2C9 CYP2D6 substrate MetaSite StarDrop.

Metabolite identification study plays an important role in determining the sites of metabolic liability of new chem. entities (NCEs) in drug discovery for lead optimization. Here we compare the two predictive software, MetaSite and StarDrop, available for this purpose. They work very differently but are used to predict the site of oxidation by major human cytochrome P 450 (CYP) isoforms. Neither software can predict non-CYP catalyzed metabolism nor the rates of metabolism For the purpose of comparing the two software packages, we tested known probe substrate for these enzymes, which included 12 substrates of CYP3A4 and 18 substrates of CYP2C9 and CYP2D6 were analyzed by each software and the results were compared. It is possible that these known substrates were part of the training set but we are not aware of it. To assess the performance of each software we assigned a point system for each correct prediction. The total points assigned for each CYP isoform exptl. were compared as a percentage of the total points assigned theor. for the first choice prediction for all substrates for each isoform. Our results show that MetaSite and StarDrop are similar in predicting the correct site of metabolism by CYP3A4 (78% vs 83%, resp.). StarDrop appears to do slightly better in predicting the correct site of metabolism by CYP2C9 and CYP2D6 metabolism (89% and 93%, resp.) compared to MetaSite (63% and 70%, resp.). The sites of metabolism (SOM) from 34 inhouse NCEs incubated in human liver microsomes or human hepatocytes were also evaluated using two prediction software packages and the results showed comparable SOM predictions. What makes this comparison challenging is that the contribution of each isoform to the intrinsic clearance (Clint) is not known. Overall the software were comparable except for MetaSite performing better for CYP2D6 and that MetaSite has a liver model that is absent in StarDrop that predicted with 82% accuracy.

Combinatorial Chemistry & High Throughput Screening published new progress about Computer program (MetaSite). 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, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

Patel, Pitambar’s team published research in Journal of Organic Chemistry in 2022-04-01 | CAS: 1468-83-3

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, SDS of cas: 1468-83-3.

Patel, Pitambar published the artcileWater-Mediated ortho-Carboxymethylation of Aryl Ketones under Ir(III)-Catalytic Conditions: Step Economy Total Synthesis of Cytosporones A-C, SDS of cas: 1468-83-3, the main research area is aryl ketone diazotized Meldrum’s acid iridium carboxymethylation alkylation mechanism; carboxymethyl acetophenone preparation; cytosporone total synthesis.

An expeditious Ir(III)-catalyzed carboxymethylation of aryl ketone with diazotized Meldrum’s acid has been developed in aqueous medium. Flavanone and chromanone were also found to be facile substrates with the developed catalytic system. Mechanistic studies revealed the active catalytic species and the role of water in the reaction process as hydroxy and proton sources. Employing the developed method, total synthesis of cytosporone A was achieved in two steps and that of cytosporones B-C was achieved in three steps starting from resorcinol.

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, SDS of cas: 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

Dang, Na Le’s team published research in Chemical Research in Toxicology in 2017-04-17 | CAS: 40180-04-9

Chemical Research in Toxicology published new progress about Biological detoxification. 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.

Dang, Na Le published the artcileComputational Approach to Structural Alerts: Furans, Phenols, Nitroaromatics, and Thiophenes, Formula: C13H8Cl2O4S, the main research area is furan phenol nitroarom thiophene metabolism toxicity modeling toxicophore.

Structural alerts are commonly used in drug discovery to identify mols. likely to form reactive metabolites, and thereby become toxic. Unfortunately, as useful as structural alerts are, they do not effectively model if, when, and why metabolism renders safe mols. toxic. Toxicity due to a specific structural alert is highly conditional, depending on the metabolism of the alert, the reactivity of its metabolites, dosage, and competing detoxification pathways. A systems approach, which explicitly models these pathways, could more effectively assess the toxicity risk of drug candidates. In this study, the authors demonstrated that math. models of P 450 metabolism can predict the context-specific probability that a structural alert will be bioactivated in a given mol. This study focuses on the furan, phenol, nitroarom., and thiophene alerts. Each of these structural alerts can produce reactive metabolites through certain metabolic pathways, but not always. The authors tested whether the metabolism modeling approach, XenoSite, can predict when a given mol.’s alerts will be bioactivated. Specifically, the authors used models of epoxidation, quinone formation, reduction, and sulfur-oxidation to predict the bioactivation of furan-, phenol-, nitroarom.-, and thiophene-containing drugs. The authors’ models separated bioactivated and not-bioactivated furan-, phenol-, nitroarom.-, and thiophene-containing drugs with AUC performances of 100%, 73%, 93%, and 88%, resp. Metabolism models accurately predict whether alerts are bioactivated and thus serve as a practical approach to improve the interpretability and usefulness of structural alerts. The authors expect that this same computational approach can be extended to most other structural alerts and later integrated into toxicity risk models. This advance is one necessary step towards the authors’ long-term goal of building comprehensive metabolic models of bioactivation and detoxification to guide assessment and design of new therapeutic mols.

Chemical Research in Toxicology published new progress about Biological detoxification. 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

 

Bonierbale, Eric’s team published research in Chemical Research in Toxicology in 1999-03-31 | CAS: 40180-04-9

Chemical Research in Toxicology published new progress about Caseins Role: ADV (Adverse Effect, Including Toxicity), BUU (Biological Use, Unclassified), RCT (Reactant), BIOL (Biological Study), USES (Uses), RACT (Reactant or Reagent) (conjugate with tienilic acid). 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.

Bonierbale, Eric published the artcileOpposite Behaviors of Reactive Metabolites of Tienilic Acid and Its Isomer toward Liver Proteins: Use of Specific Anti-Tienilic Acid-Protein Adduct Antibodies and the Possible Relationship with Different Hepatotoxic Effects of the Two Compounds, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is tienilic acid hepatotoxicity immunity cytochrome P450.

Tienilic acid (TA) is responsible for an immune-mediated drug-induced hepatitis in humans, while its isomer (TAI) triggers a direct hepatitis in rats. In this study, we describe an immunol. approach developed for studying the specificity of the covalent binding of these two compounds For this purpose, two different coupling strategies were used to obtain TA-carrier protein conjugates. In the first strategy, the drug was linked through its carboxylic acid function to amine residues of carrier proteins (BSA-N-TA and casein-N-TA), while in the second strategy, the thiophene ring of TA was attached to proteins through a short 3-thiopropanoyl linker, the corresponding conjugates (BSA-S-5-TA and βLG-S-5-TA) thus preferentially presenting the 2,3-dichlorophenoxyacetic moiety of the drug for antibody recognition. The BSA-S-5-TA conjugate proved to be 30 times more immunogenic than BSA-N-TA. Anti-TA-protein adduct antibodies were obtained after immunization of rabbits with BSA-S-5-TA (1/35000 titer against βLG-S-5-TA in ELISA). These antibodies strongly recognized the 2,3-dichlorophenoxyacetic moiety of TA but poorly the part of the drug engaged in the covalent binding with the proteins. This powerful tool was used in immunoblots to compare TA or TAI adduct formation in human liver microsomes as well as on microsomes from yeast expressing human liver cytochrome P 450 2C9. TA displayed a highly specific covalent binding focused on P 450 2C9 which is the main cytochrome P 450 responsible for its hepatic activation in humans. On the contrary, TAI showed a nonspecific alkylation pattern, targeting many proteins upon metabolic activation. Nevertheless, this nonspecific covalent binding could be completely shifted to a thiol trapping agent like GSH. The difference in alkylation patterns for these two compounds is discussed with regard to their distinct toxicities. A relationship between the specific covalent binding of P 450 2C9 by TA and the appearance of the highly specific anti-LKM2 autoantibodies (known to specifically recognize P 450 2C9) in patients affected with TA-induced hepatitis is strongly suggested.

Chemical Research in Toxicology published new progress about Caseins Role: ADV (Adverse Effect, Including Toxicity), BUU (Biological Use, Unclassified), RCT (Reactant), BIOL (Biological Study), USES (Uses), RACT (Reactant or Reagent) (conjugate with tienilic acid). 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