Heterocyclic Building Blocks-Benzothiophene

Lim, Heng-Keang published the artcileAutomated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is inactivation cytochrome CYP3A4 CYP2C9 CYP2C19 CYP2D6 CYP1A2 microsome.

A strategy is proposed to profile compounds for mechanism-based inactivation of CYP3A4, CYP2C19, CYP2C9, CYP2D6, and CYP1A2 based on an apparent partition ratio screen. Potent positives from the screen are confirmed by time- and concentration-dependent inactivation assays. Quasi-irreversible inhibitions are then differentiated from irreversible inactivations by oxidation with potassium ferricyanide and/or dialysis. The three-step screening procedure has been validated with acceptable accuracy and precision for detection and confirmation of mechanism-based inactivators in drug discovery. We report here the apparent partition ratios for 19 mechanism-based inactivators and four quasi-irreversible inhibitors obtained under the same exptl. conditions. The apparent partition ratio screen was automated to provide throughput for determining structure-mechanism-based inactivation relationships. Information about reversibility can be used to assess potential toxicity mediated by covalent adducts, as well as the potential for pharmacokinetic drug-drug interactions. Direct comparison of known mechanism-based inactivators and quasi-irreversible inhibitors, based on our screening of apparent partition ratios, has identified ritonavir, mibefradil, and azamulin as highly effective mechanism-based inactivators; e.g., 1 mol of CYP3A4 was inactivated on turnover of about 2 mol of compound Other mechanism-based inactivators we identified include bergamottin (CYP1A2 besides previously reported CYP3A4), troglitazone (CYP3A4), rosiglitazone (CYP3A4), and pioglitazone (CYP3A4). Comparison of the apparent partition ratios and inactivation clearance data for the three glitazones suggests that the chromane moiety on troglitazone contributes to its greater potency for mechanism-based inactivation.

Drug Metabolism and Disposition published new progress about Enzyme inhibition 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, Safety of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Han, Zhengyu published the artcileEnantiodivergent Synthesis of Chiral Tetrahydroquinoline Derivatives via Ir-Catalyzed Asymmetric Hydrogenation: Solvent-Dependent Enantioselective Control and Mechanistic Investigations, COA of Formula: C6H6OS, the main research area is chiral tetrahydroquinoline preparation enantioselective; quinoline hydrogenation iridium catalyst.

Ir-catalyzed asym. hydrogenation of quinolines I (R = Me, Ph, naphthalen-2-yl, 2H-1,3-benzodioxol-5-yl, thiophen-3-yl, etc.; R1 = H, Me, Et, n-Pr; R2 = H, 5-Cl, 6-OMe, 7-Me, etc.) was developed, and both enantiomers of chiral tetrahydroquinoline derivatives ((R)/(S)/cis/trans)-II could be easily obtained, resp., in high yields with good enantioselectivities through the adjustment of reaction solvents (toluene/dioxane: up to 99% yield, 98% ee (R), TON = 680; EtOH: up to 99% yield, 94% ee (S), TON = 1680). It provided an efficient and simple synthetic strategy for the enantiodivergent synthesis of chiral tetrahydroquinolines ((R)/(S)/cis/trans)-II, and gram-scale asym. hydrogenation proceeded well with low-catalyst loading in these two reaction systems. A series of deuterium-labeling experiments, control experiments, and 1H NMR and electrospray ionization-mass spectrometry experiments have been conducted, and a reasonable and possible reaction process was revealed on the basis of these useful observations.

ACS Catalysis published new progress about Enantioselective synthesis. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, COA of Formula: C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Rossato, Gianluca published the artcileProbing Small-Molecule Binding to Cytochrome P450 2D6 and 2C9: An In Silico Protocol for Generating Toxicity Alerts, Related Products of benzothiophene, the main research area is pharmacophore QSAR metabolism CYP2D6 CYP2C9 binding screening interaction toxicity.

Drug metabolism, toxicity, and their interaction profiles are major issues in the drug-discovery and lead-optimization processes. The cytochromes P 450 (CYPs) 2D6 and 2C9 are enzymes involved in the oxidative metabolism of a majority of marketed drugs. Therefore, the prediction of the binding affinity towards CYP2D6 and CYP2C9 would be beneficial for identifying cytochrome-mediated adverse effects triggered by drugs or chems. (e.g., toxic reactions, drug-drug, and food-drug interactions). By identifying the binding mode by using pharmacophore prealignment, automated flexible docking, and by quantifying the binding affinity by multidimensional QSAR (mQSAR), we validated a model family of 56 compounds (46 training, 10 test) and 85 compounds (68 training, 17 test) for CYP2D6 and CYP2C9, resp. The correlation with the exptl. data (cross-validated r2=0.811 for CYP2D6 and 0.687 for CYP2C9) suggests that our approach is suited for predicting the binding affinity of compounds towards CYP2D6 and CYP2C9. The models were challenged by Y-scrambling and by testing an external dataset of binding compounds (15 compounds for CYP2D6 and 40 for CYP2C9). To assess the probability of false-pos. predictions, datasets of nonbinders (64 compounds for CYP2D6 and 56 for CYP2C9) were tested by using the same protocol. The two validated mQSAR models were subsequently added to the VirtualToxLab (VTL, ).

ChemMedChem published new progress about Drug interactions, adverse. 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

Shen, Jiabin published the artcileSelective Mono- and Diamination of Ketones in a Combined Copper-Organocatalyst System, Recommanded Product: 3-Acetylthiophene, the main research area is pyrazole ketone chemoselective preparation; ketone azole copper organocatalyst mono amination; dipyrazole ketone chemoselective preparation; azole ketone copper organocatalyst di amination.

Herein, a simple and mild protocol for syntheses of α-pyrazoles I [R = 4-Me, 5-I, 3-Ph, etc.; Ar = Ph, 3-MeC6H4, 4-ClC6H4, etc.] and α,α-dipyrazole ketone derivatives II [R2 = R3 = H, 4-Cl, 4-Br, etc.; Ar1 = Ph, 3-FC6H4, 4-ClC6H4, etc.] via combined copper-organocatalyzed chemoselective mono- and diamination of ketones using azoles as amine source were reported. Various substrates were compatible and provided the corresponding products I and II in moderate to good yields.

Organic Letters published new progress about Amination (chemoselective). 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

Tanaka, Toshimasa published the artcileCharacterization of the CYP2C8 active site by homology modeling, Quality Control of 40180-04-9, the main research area is CYP2C8 active site homol model pharmacophore CYP2C9 CYP2C19.

To compare the features of the active sites of CYP2C8, CYP2C9, and CYP2C19, homol. modeling was performed based on the crystallog. coordinates of mammalian CYP2C5. It was found that CYP2C8 has a much larger pocket than the other forms due to the existence of an addnl. pocket. The approach to the addnl. pocket is comprised of Ile102, Ser114, Leu208, Val366, and Ile476, and the side chains of Ser114, Val366, and Ile476, which are smaller than the corresponding residues in the other CYPs, enable access to the pocket. The general features of the active site in the CYP2C8 model are similar to those of the previously constructed CYP3A4 model, which may account for the 2 CYPs sharing some of their substrates. The CYP2C8 model was validated by examining the bound orientation of paclitaxel and showing that it is consistent with the formation of the 6-beta hydroxylated derivative during metabolism Docked paclitaxel was found to form a hydrogen bond with the side chain of Asn99, which is a characteristic residue of CYP2C8 and is located in the addnl. pocket. Descriptors for CYP2C8 and CYP2C9 substrates were also examined with the mol. operating environment (MOE). The descriptor by which CYP2C8 and CYP2C9 substrates were classified most distinctly was found to be molar refractivity, which might be related to the longer shape and more polar nature of the active site of CYP2C8 in the CYP2C subfamily.

Chemical & Pharmaceutical Bulletin published new progress about Conformation (homol. model). 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

Gao, Ya published the artcileDefluorinative Alkylation of Trifluoromethyl Alkenes with Soft Carbon Nucleophiles Enabled by a Catalytic Amount of Base, COA of Formula: C6H6OS, the main research area is gem difluoroalkene fluoro pyran preparation; trifluoromethyl alkene soft carbon nucleophile defluorinative alkylation.

Direct manipulation of readily accessible trifluoromethyl alkenes (TAs) represents an attractive approach to the preparation of diversified fluorine-containing compounds In this study, defluorinative alkylation reactions of TAs with a broad array of soft carbon nucleophiles have been documented. Nucleophilic substitutions occur enabled by a catalytic amount of base, providing access to tertiary alkyl substituted gem-difluoroalkenes and 2-fluoro-4H-pyrans. By extending the nucleophiles to silyl enol ethers, defluorination can be achieved in the absence of base to give gem-difluoroalkenes. This process, which eliminates the requirement of organometallic reagents, transition metals, or strong bases for the C-F bond cleavage, is applicable to late-stage modification of complex mols.

Advanced Synthesis & Catalysis published new progress about Alkylation (defluorinative). 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, COA of Formula: C6H6OS.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Fagbemi, Kehinde Oluwakemi published the artcileBioactive compounds, antibacterial and antioxidant activities of methanol extract of Tamarindus indica Linn., Application In Synthesis of 1468-83-3, the main research area is Tamarindus indica methanol extract bioactive compound antibacterial antioxidant activity.

Tamarindus indica is one of the tropical medicinal plants that has been attributed curative potential of numerous diseases by many rural dwellers. This study was designed to evaluate the antioxidant, antibacterial activities and also to determine the various chem. constituents responsible for its pharmacol. activities. The methanol extract of Tamarindus indica fruit pulp was analyzed by Gas Chromatog./Mass Spectrometer to determine the volatile compounds present. The antioxidant activities were performed using DPPH and FRAP method and the antibacterial activity was tested against some common pathogens by macro broth dilution method. The GCMS anal. shows the presence of 37 compounds, out of which 14 had their peak area percentages ≥ 1% and only two compounds had no reported pharmacol. activities. Most of the bioactive compounds including 5-Hydroxymethylfurfural (31.06%)-3-O-Methyl-d-glucose (16.31%), 1,6-anhydro-β-D-Glucopyranose (9.95%), 5-methyl-Furancarboxaldehyde (3.2%), Triethylenediamine (1.17%), 1-(2-furanyl)-1-Propcanone (2.18%), Me 2-furoate (3.14%), Levoglucosenone (3.21%), Me ester-Hepta-2,4-dienoic acid, (8.85%), 2,3-dihydro-3,5-dihydrox-4H-Pyran-4-one (3.4%), O-α-D-glucopyranosyl-(1.fwdarw.3)-β-D-fructofuranosyl-α-D-Glucopyranoside (2.18%), n-Hexadecanoic acid (1.38%), 2-Heptanol, acetate (1.29%), 5-[(5-methyl-2-fur-2-Furancarboxaldehyde)] (1.08%), 3-Methyl-2-furoic acid (1.05%) and cis-Vaccenic acid (2.85%)have been reported with different activities such as antibacterial, antifungal, antitubercular, anticancer, antioxidant and other prophylactic activities. The extract demonstrated inhibitory potential against all tested pathogen. However, Plesiomonas shigellosis ATCC 15903 and Bacillus pumillus ATCC 14884 are more sensitive with the MIC of 0.22 and 0.44 mg/mL resp. The antioxidant activity was relatively low due to the low phenolic content of the extract This shows that there is a strong correlation between antioxidant activities and phenolic content. GC-MS anal. revealed the presence of bioactive phytoconstituents with various biol. activities and this justifies the rationale behind its usage as a curative therapy by many local dwellers.

Scientific Reports published new progress about Acinetobacter calcoaceticus. 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

Xing, Yidan published the artcileSynthesis of Tertiary Benzylic Nitriles via Nickel-Catalyzed Markovnikov Hydrocyanation of α-Substituted Styrenes, Safety of 3-Acetylthiophene, the main research area is benzylic nitrile preparation Markovnikov hydrocyanation styrene nickel catalyst.

The Markovnikov hydrocyanation of α-substituted styrenes enables the synthesis of tertiary benzylic nitriles under nickel catalysis. The Lewis-acid-free transformation features an unprecedented functional groups tolerance, including the -OH and -NH2 groups. A broad range of tertiary benzylic nitriles were obtained in good to excellent yields. In addition, an asym. version of this reaction was preliminarily investigated.

Organic Letters published new progress about Hydrocyanation (Markovnikov). 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

Huang, Yubing published the artcileTransition-metal-free N-difluoromethylation of hydrazones with TMSCF2Br as the difluoromethylation reagent, SDS of cas: 1468-83-3, the main research area is tosyl hydrazone bromodifluoromethyl trimethylsilane difluoromethylation.

A novel and practical protocol to synthesize a series of N-difluoromethyl hydrazones via base-promoted N-difluoromethylation was reported. With hydrazones as chain substrates containing N-N bonds and TMSCF2Br as the difluoromethylation reagent, the reaction delivers N-difluoromethyl hydrazones in good yields, which exhibit good functional group tolerance and stereoselectivity.

Organic Chemistry Frontiers published new progress about Diastereoselective synthesis. 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

Xu, Jun published the artcileA combination of heterogeneous catalysis and photocatalysis for the olefination of quinoxalin-2(1H)-ones with ketones in water: a green and efficient route to (Z)-enaminones, Safety of 3-Acetylthiophene, the main research area is enaminone quinoxalinone acylmethylene preparation diastereoselective green chem; quinoxalinone diastereoselective photochem olefination ketone.

Herein, a novel aqueous reaction for the olefination of quinoxalin-2(1H)-ones I (R1 = H, 5-Me, 6-OMe, 6,7-Cl2, etc.; R2 = H, Me, cyclohexylmethyl, allyl, Ph, 2,6-F2C6H3CH2, etc.) with ketones R3C(O)CH2R4 [R3 = Me, cyclopropyl, Ph, 3-thienyl, etc., R4 = H; R3R4 = (CH2)3, CH(cyclopentyl)CH2CH2] through a combinational strategy is described. This reaction features very mild conditions using a simple and cheap catalyst for the synthesis of (Z)-enaminones II in moderate-to-good yields. Such a methodol. successfully combines the heterogeneous Mannich reaction with photocatalysis, and provides a green and practical approach for the synthesis of potentially bioactive (Z)-enaminones with a 3,4-dihydroquinoxalin-2(1H)-one skeleton.

Green Chemistry published new progress about Diastereoselective synthesis. 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