Heterocyclic Building Blocks-Benzothiophene

Dan, Takashi published the artcileMechanism of uricosuric action of AA-193 in DBA/2N mice, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is AA193 uricosuric urate mouse.

Six strains of mice were investigated to find an animal model suitable for researching the mechanism of uricosuric agents. A clearance method and a pyrazinamide suppression test were used to examine the mechanism of urate excretion in the kidney and the mode of action of uricosurics, resp. The neg. correlation between the urinary urate excretion and the endogenous plasma urate level was observed, suggesting the net reabsorption of urate may vary between strains. DBA/2N mice showed the lowest fractional excretion of urate (0.278), and the effects of uricosurics on DBA/2N mice are analogous to those of human. This mouse strain is a useful model for the study of uricosurics. AA-193 (I), a potent new uricosuric agent, was tested in DBA/2N mice and found to have a mode of action different from well-known uricosuric agents. It appeared to inhibit presecretory reabsorption in the proximal tubules.

Journal of Pharmacology and Experimental Therapeutics published new progress about Diuresis. 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

Stote, R. M. published the artcileTicrynafen: site of natriuretic activity, Product Details of C13H8Cl2O4S, the main research area is ticrynafen diuresis natriuresis mechanism.

In normal subjects given ticrynafen (I) [40180-04-9] 500 and 1000 mg oral doses under conditions of water diuresis, there was a decrease in free water excretion as osmolar clearance increased. During hydropenia, there was no change in free-water reabsorption as osmolar clearance increased. Maximum Na excretion reached 5.2% of the filtered load. At 500 mg doses, there was no effect on phosphate excretion; with 1000 mg doses, there was a reduction in phosphate excretion. During bicarbonate infusion, there was no change in the absolute or percent reabsorption of bicarbonate. After chronic administration of I, there was no impairment of excretion of an acute acid load. Uric acid excretion increased at least 3-fold in all studies. Thus, at 500 and 1000 mg oral doses, I has the characteristics of a diuretic which is active in the cortical diluting segment of the distal nephron.

Nephron published new progress about Diuresis. 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

Parkinson, Andrew published the artcileAn evaluation of the dilution method for identifying metabolism-dependent inhibitors of cytochrome P450 enzymes, Quality Control of 40180-04-9, the main research area is liver microsome dilution cytochrome P450 inhibitor metabolism.

Metabolism-dependent inhibition (MDI) of cytochrome P 450 is usually assessed in vitro by examining whether the inhibitory potency of a drug candidate increases after a 30-min incubation with human liver microsomes (HLMs). To augment the IC50 shift, many researchers incorporate a dilution step whereby the samples, after being preincubated for 30 min with a high concentration of HLMs (with and without NADPH), are diluted before measuring P 450 activity. In the present study, we show that the greater IC50 shift associated with the dilution method is a consequence of data processing. With the dilution method, IC50 values for direct-acting inhibitors vary with the dilution factor unless they are based on the final (postdilution) inhibitor concentration, whereas the IC50 values for MDIs vary with the dilution factor unless they are based on the initial (predilution) concentration When the latter data are processed on the final inhibitor concentration, as is commonly done, the IC50 values for MDI (shifted IC50 values) decrease by the magnitude of the dilution factor. The lower shifted IC50 values are a consequence of data processing, not enhanced P 450 inactivation. In fact, for many MDIs, increasing the concentration of HLMs actually leads to considerably less P 450 inactivation because of inhibitor depletion and/or binding of the inhibitor to microsomes. A true increase in P 450 inactivation and IC50 shift can be achieved by assessing MDI by a nondilution method and by decreasing the concentration of HLMs. These results have consequences for the conduct of MDI studies and the development of cut-off criteria.

Drug Metabolism and Disposition published new progress about Dilution. 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

Hiremath, Chaitanya N. published the artcileAbbreviated Profile of Drugs (APOD): modeling drug safety profiles to prioritize investigational COVID-19 treatments, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is abbreviated profile drug APOD modeling safety profiles prioritize investigational; ADMET; Abbreviated Profile of Drugs (APOD); COVID-19; Drug discovery; Drug safety profile; Pharmacokinetic prediction.

Safe and effective oral formulation of a drug that is easy to store, transport, and administer, is imperative to reach the masses including those without adequate facilities and resources, in order to combat globally transmitted coronavirus disease 2019 (COVID-19). In this decision analytic modeling study, the safety of investigational COVID-19 drugs in clin. trials was assessed using the Abbreviated Profile of Drugs (APOD) methodol. The method was extensively tested for various unbiased datasets based on different criteria such as drugs recalled worldwide for failing to meet safety standards, organ-specific toxicities, cytochrome P 450 inhibitors, and Food and Drug Administration (FDA) approved drugs with remarkable successes. Exptl. validation of the predictions made by APOD were demonstrated by comparison with a progression of multiparametric optimization of a series of cancer drugs that led to a potent drug (GDC-0941) which went into the clin. development. The drugs were classified into three categories of safety profiles: strong, moderate and weak. A total of 3556 drugs available in public databases were examined According to the results, drugs with strong safety profiles included molnupiravir (EIDD-2801), moderate safety profiles included dexamethasone, and weak safety profiles included lopinavir. In this anal., the physicochem.-pharmacokinetic APOD fingerprint was associated with the drug safety profile of withdrawn, approved, as well as drugs in clin. trials and the APOD method facilitated decision-making and prioritization of the investigational treatments.

Heliyon published new progress about COVID-19. 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

Marko, Jason A. published the artcileElectrochemical benzylic oxidation of C-H bonds, HPLC of Formula: 1468-83-3, the main research area is electrochem benzylic oxidation carbon hydrogen bond.

Oxidized products have become increasingly valuable as building blocks for a wide variety of different processes and fine chem., especially in the benzylic position. The authors report herein a sustainable protocol for this transformation through C-H functionalization and was performed using electrochem. as the main power source and tert-Bu hydroperoxide as the radical source for the C-H abstraction. The temperature conditions reported here do not increase >50° and use an aqueous-based medium. A broad substrate scope is explored, along with bioactive mols., to give comparable and increased product yields when compared to prior reported literature without the use of electrochem.

Chemical Communications (Cambridge, United Kingdom) published new progress about C-H bond. 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

Bell, Leslie published the artcileEvaluation of fluorescence- and mass spectrometry-based CYP inhibition assays for use in drug discovery, COA of Formula: C13H8Cl2O4S, the main research area is cytochrome P450 drug discovery fluorescence mass spectrometry bioassay.

The potential for metabolism-related drug-drug interactions by new chem. entities is assessed by monitoring the impact of these compounds on cytochrome P 450 (CYP) activity using well-characterized CYP substrates. The conventional gold standard approach for in vitro evaluation of CYP inhibitory potential uses pooled human liver microsomes (HLM) in conjunction with prototypical drug substrates, often quantified by LC-MS/MS. However, fluorescent CYP inhibition assays, which use recombinantly expressed CYPs and fluorogenic probe substrates, have been employed in early drug discovery to provide low-cost, high-throughput assessment of new chem. entities. Despite its greatly enhanced throughput, this approach has been met with mixed success in predicting the data obtained with the conventional gold standard approach (HLM+LC-MS). The authors find that the predictivity of fluorogenic assays for the major CYP isoforms 3A4 and 2D6 may depend on the quality of the test compounds Although the structurally more optimized marketed drugs yielded acceptable correlations between the fluorogenic and HLM+LC-MS/MS assays for CYPs 3A4, 2D6, and 2C9 (r2 = 0.5-0.7; p < 0.005), preoptimization, early discovery compounds yielded poorer correlations (r2 ≤ 0.2) for 2 of these major isoforms, CYPs 3A4 and 2D6. Potential reasons for the observed differences are discussed. Journal of Biomolecular Screening published new progress about Bioassay. 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

Saiakhov, Roustem published the artcileEffectiveness of CASE Ultra Expert System in Evaluating Adverse Effects of Drugs, COA of Formula: C13H8Cl2O4S, the main research area is quant structure activity relationship drug withdrawal toxicity; Adverse effects; CASE Ultra; Expert systems; QSAR; Risk assessment; in silico.

Purpose of this pilot study is to test the QSAR expert system CASE Ultra for adverse effect prediction of drugs. 870 drugs from the SIDER adverse effect dataset were tested using CASE Ultra for carcinogenicity, genetic, liver, cardiac, renal and reproductive toxicity. 47 drugs that were withdrawn from market since the 1950s were also evaluated for potential risks using CASE Ultra and compared them with the actual reasons for which the drugs were recalled. For the whole SIDER test set (n=870), sensitivity and specificity of the carcinogenicity predictions are 66.67 % and 82.17 % resp.; for liver toxicity: 78.95 %, 78.50 %; cardiotoxicity: 69.07 %, 57.57 %; renal toxicity: 46.88 %, 67.90 %; and reproductive toxicity: 100.00 %, 61.10 %. For the SIDER test chems. not present in the training sets of the models, sensitivity and specificity of carcinogenicity predictions are 100.00 % and 88.89 % resp. (n=404); for liver toxicity: 100.00 %, 51.33 % (n=115); cardiotoxicity: 100.00 %, 20.45 % (n=94); renal toxicity: 100.00 %, 45.54 % (n=115); and reproductive toxicity: 100.00 %, 48.57 % (n=246). CASE Ultra correctly recognized the relevant toxic effects in 43 out of the 47 withdrawn drugs. It predicted all 9 drugs that were not part of the training set of the models, as unsafe.

Molecular Informatics published new progress about Behavior. 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

Huang, Tao published the artcilePrediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles, Quality Control of 40180-04-9, the main research area is xenobiotic drug discovery toxicity prognosis.

More and more people are concerned by the risk of unexpected side effects observed in the later steps of the development of new drugs, either in late clin. development or after marketing approval. To reduce the risk of the side effects, it is important to look out for the possible xenobiotic responses at an early stage. The authors attempt such an effort through a prediction by assuming that similarities in microarray profiles indicate shared mechanisms of action and/or toxicol. responses among the chems. being compared. A large time course microarray database derived from livers of compound-treated rats with thirty-four distinct pharmacol. and toxicol. responses were studied. The mRMR (Min.-Redundancy-Maximum-Relevance) method and IFS (Incremental Feature Selection) were used to select a compact feature set (141 features) for the reduction of feature dimension and improvement of prediction performance. With these 141 features, the Leave-one-out cross-validation prediction accuracy of first order response using NNA (Nearest Neighbor Algorithm) was 63.9%. The authors’ method can be used for pharmacol. and xenobiotic responses prediction of new compounds and accelerate drug development.

PLoS One published new progress about Basophil. 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

Fujimoto, Kazunori published the artcileIn vitro cytotoxicity assay to evaluate the toxicity of an electrophilic reactive metabolite using glutathione-depleted rat primary cultured hepatocytes, Quality Control of 40180-04-9, the main research area is cytotoxicity assay glutathione depleted hepatocyte.

Glutathione plays an important role as not only a scavenger of reactive oxygen species but also in the conjugation or detoxification of electrophilic reactive metabolites, which has been thought to be one of the causes for idiosyncratic drug toxicity (IDT). Therefore, toxic responses to the reactive metabolites have been expected to be expressed more strongly in a glutathione-depleted condition. In the present study, we attempted to establish an in vitro cytotoxicity assay method to evaluate the toxicity of the reactive metabolite using rat primary cultured hepatocytes with cellular glutathione depletion by L-buthionine-S,R-sulfoximine. Also, we investigated whether the IDT risk is predictable by comparing the cytotoxic sensitivity between glutathione-depleted hepatocytes and untreated hepatocytes. Consequently, 10 drugs of 42 approved drugs, which were classified into 4 IDT categories (Withdrawn, Black box warning, Warning, and Safe), demonstrated higher cytotoxic sensitivity in the glutathione-depleted hepatocytes. Furthermore, a correlation was observed between the incidence of drugs with higher cytotoxic sensitivity in the glutathione-depleted hepatocytes and the IDT risk. The incidence was 50% in the Withdrawn category, 38% in the Black box warning category, 22% in the Warning category, and 8% in the Safe category. These results suggest that the IDT risk of some drugs may be predicted by comparing the cytotoxic sensitivity between them. Addnl., this method may be useful as a screening in the early stage of drug development where leads/candidates are optimized.

Chemico-Biological Interactions published new progress about Analysis. 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

Valadon, Philippe published the artcileThiophene Sulfoxides as Reactive Metabolites: Formation upon Microsomal Oxidation of a 3-Aroylthiophene and Fate in the Presence of Nucleophiles in Vitro and in Vivo, Related Products of benzothiophene, the main research area is microsome oxidation tienilic acid.

Oxidative metabolism of the 3-aroylthiophene tienilic acid (I) by rat liver microsomes in the presence of mercaptoethanol as a trapping agent led to the isolation of four main compounds, which have been isolated and characterized by UV, 1H NMR, and mass spectroscopy. They all derive from two primary metabolites (II diastereoisomers), which result from the nucleophilic addition of mercaptoethanol to a reactive, very electrophilic intermediate formed by sulfoxidation of the thiophene ring of I. Further reactions of II diastereoisomers with mercaptoethanol led a compound that is opened at the level of its thiophene ring and, eventually, to a final metabolite III, resulting formally from the addition of mercaptoethanol on the 4,5-double bond of the thiophene ring of I. III is very stable even in the presence of a large excess of mercaptoethanol. Similar reactions were observed upon microsomal oxidation of I in the presence of another thiol, N-acetylcysteine. Final metabolites (IV diastereoisomers), equivalent to III, except for the replacement of its mercaptoethanol substituent with an N-acetylcysteinyl group, were isolated and characterized by UV, 1H NMR, and mass spectroscopy. After treatment of rats with I, IV could be detected in urine, indicating that the successive reactions, that were observed in vitro after microsomal oxidation of I in the presence of a thiol-containing trapping agent, also occur in vivo, glutathione acting as a nucleophile in that case. These data provide evidence for the intermediate formation of a reactive, electrophilic thiophene sulfoxide in metabolic oxidation of I in vitro and in vivo. They also provide the first data on the complex reactivity of such thiophene sulfoxides, whose chem. is poorly known, and on their fates in living organisms.

Chemical Research in Toxicology published new progress about Microsome. 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