Day: November 18, 2022

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using CASE Ultra for carcinogenicity, genetic, liver, cardiac, renal and reproductive toxicity. 47 drugs that were withdrawn from market since the 1950s were also evaluated for potential risks using CASE Ultra and compared them with the actual reasons for which the drugs were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 CASE Ultra correctly recognized the relevant toxic effects in 43 out of the 47 withdrawn drugs.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

Koga, Hiroshi published the artcileStudies on uricosuric diuretics. 4. Three-dimensional structure-activity relationships and receptor mapping of (aryloxy)acetic acid diuretics, Formula: C13H8Cl2O4S, the main research area is aryloxyacetate diuretic structure activity receptor model.

A receptor model was created for (aryloxy)acetic acid diuretics based on the enhanced diuretic activity of indacrinone (I) and a tienilic acid analog (II) when compared with tienilic acid (III). The degree of fitting to this receptor model was related to the diuretic activity of a series of (aryloxy)acetic acid analogs. Studies with addnl. analogs led to a modification of the receptor model which should be useful for future drug design.

Journal of Medicinal Chemistry published new progress about Diuretics. 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

Ehrhardt, J. D. published the artcileNegative-ion mass spectra of methylated diuretics, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is diuretic methylation mass spectra analysis.

The neg.-ion mass spectra of 19 methylated diuretics are presented and correlations between these spectra and the chem. structures of the compounds are indicated. The spectra are of interest as the basis of an anal. method for the identification of small quantities of diuretics in the urine of hypokalemic patients.

Rapid Communications in Mass Spectrometry published new progress about Diuretics. 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

Ahokas, Jorma T. published the artcileInhibition of purified rat liver glutathione S-transferase isozymes by diuretic drugs, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is glutathione transferase inhibition diuretic.

Seven soluble rat liver glutathione S-transferase  [50812-37-8] isozymes were isolated, and the inhibition of these isozymes by selected diuretics was investigated, using 1-chloro-2,4-dinitrobenzene as substrate. All the isozymes were inhibited to some extent, but there was significant isozyme-dependent selectivity of inhibition. The greatest inhibitory effect (80%) was found when phenoxyacetic acid-type diuretics and indacrynic acid  [56049-88-8] were incubated with glutathione S-transferase isozymes 3-3, 3-4, and 4-4. The sulfamoylbenzoic acid diuretics furosemide  [54-31-9] and bumetanide  [28395-03-1] had a lesser effect on the isozymes studied. As glutathione S-transferases are thought to play an important protective role in the various tissues of animals and man, by catalyzing the glutathione conjugation of electrophilic drugs and drug metabolites, their inhibition may be toxicol. important.

Biochemical Pharmacology published new progress about Diuretics. 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

Takagi, Shiro published the artcileHepatotoxicity of DR-3438, tienilic acid, indacrinone and furosemide studied in vitro, Computed Properties of 40180-04-9, the main research area is liver toxicity diuretic DR 3438; tienilic acid liver toxicity; indocrinone liver toxicity; furosemide liver toxicity.

A new diuretic antihypertensive, DR-3438 (I), and the 3 other title diuretic drugs were evaluated for their toxicity in vitro. Hepatocytes were isolated from male rats and incubated in medium containing various concentrations of DR-3438, tienilic acid, indacrinone or furosemide. Tienilic acid decreased cell viability and glutathione content in the hepatocytes and increased lipid peroxidation in these cells. Indacrinone also decreased cell viability, but neither cell viability nor glutathione content was affected by furosemide or DR-3438.

Toxicology Letters published new progress about Diuretics. 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

Higaki, Junko published the artcileChemical structure and toxicity of diuretics in isolated hepatocytes, Formula: C13H8Cl2O4S, the main research area is diuretic structure hepatocyte toxicity; tienilic acid analog structure activity; indacrinone analog structure activity.

The effects of several diuretics, including tienillic acid (I) and indacrinone (II) on isolated rat hepatocytes were examined Addition of I and II at 1 mM to a suspension of freshly isolated cells caused dose-dependent loss of cell viability as judged by the LDH-latency test. A survey of 19 structurally related compounds [III, IV, and V (R = 2-thienylcarbonyl, EtCO, Me2NSO2, MeNHSO2, or H2NSO2, X and Y = H, Cl, or Me)] revealed that the extent of cell injury and chem. structure were correlated, and an intense adverse effect was attributed to the 2-thienylcarbonyl moiety. Several other factors influencing cell viability are also disclosed. I and II were toxic to the primary culture of hepatocytes at a lower dose than that to freshly isolated hepatocytes. Thus, an isolated hepatocyte system can be used to select compounds displaying low hepatotoxicity, e.g., when screening diuretics.

Pharmacology & Toxicology (Oxford, United Kingdom) published new progress about Diuretics. 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

Tolman, Keith G. published the artcileToxicity of uricosuric diuretics in rat hepatocyte culture, Category: benzothiophene, the main research area is uricosuric toxicity liver hepatocyte structure.

Several aryloxyacetic acid diuretics have shown hepatotoxicity in humans, yet there continues to be interest in developing these compounds because of their uricosuric properties. The hepatocyte monolayer culture associated, as a model for studying the compounds in vitro. An attempt was made to define the structural components that are associated with hepatotoxicity. Ticrynafen, indacrinone, ethacrynic acid, and A-49816 were toxic in hepatocyte cultures. With the exception of indacrinone, the toxicity was paralleling the experience in humans. The toxic compounds share a ketodichlorophenoxyacetic acid chem. structure (I). A-56234, an investigational uricosuric, was also toxic in cultures but was not hepatotoxic in limited clin. experience in humans. It does not possess the I structure proper but may be metabolized to a closely related structure. Furosemide, which does not have the I structure, was not toxic in hepatocyte cultures and has not been hepatotoxic in humans. Thus, the structure common to the toxic compounds is I or a closely related compound The hepatocyte monolayer system is a good model for demonstrating toxicity and/or predicting toxicity of new compounds

Biochemical Pharmacology published new progress about Diuretics. 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, Category: benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem