Category: benzothiophene

Randolph, W. C. published the artcileHigh-pressure liquid chromatographic analysis of ticrynafen and one of its metabolites in urine and serum, Synthetic Route of 40180-04-9, the main research area is ticrynafen blood urine chromatog.

A method is described for the extraction of ticrynafen (I) [40180-04-9], a new hypotensive agent, and its reduced metabolite from serum and urine. Drug-related material is extracted from biol. fluids with ether under strongly acidic conditions and the back-extracted into an alk. aqueous phase, which is subjected to high-pressure liquid chromatog. anal. Separations are performed on a reversed-phase column with a mobile phase consisting of phosphate buffer-acetonitrile. The method measured serum concentrations of I and its reduced metabolite as low as 1.0 and 0.4 μg/mL, resp.

Journal of Pharmaceutical Sciences published new progress about Blood 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, Synthetic Route of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Waal-Manning, H. J. published the artcileOne year follow-up of hyperuricemic hypertensive patients treated with tienilic acid or a diuretic with or without uric acid-lowering drugs, Product Details of C13H8Cl2O4S, the main research area is tienilate blood pressure; serum urate tienilate; liver function tienilate.

Fifty-four hypertensive, hyperuricemic patients were pair-matched for age, sex, and current therapy (diuretic, uric acid (I) [69-93-2]-lowering drug) and one member of each pair was assigned to treatment with tienilic acid (II) [40180-04-9] (188 mg/day) while the other member continued on the previous therapy; blood pressure control was equally good in the II-treated and control groups but serum I levels were lower in II-treated patients. Liver function tests changed from pretrial results in 9 patients; minor increases in alk. phosphatase occurred in 8 of these patients (4 in the II treatment group and 4 in the control group). However the 9th patient (receiving II) showed a marked increase in serum aspartate transaminase and eventually rises in alk. phosphatase and bilirubin; these values reverted to normal after stopping II.

Clinical Science published new progress about Blood pressure. 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

Ramesh, Deepthi published the artcileFirst-in-class pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones against leishmaniasis and tuberculosis: Rationale, in vitro, ex vivo studies and mechanistic insights, Quality Control of 1468-83-3, the main research area is Pyrido pyrimidine dione leishmaniasis tuberculosis; antileishmanial antitubercular activity mol modeling; dihydrofolate reductase-thymidylate synthase complex; leishmaniasis; pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione; thymidylate kinase; tuberculosis.

Pyrido[2,3-d]pyrimidine-2,4(1H,3H)-diones were synthesized, for the first time, from indole chalcones and 6-aminouracil, and their ability to inhibit leishmaniasis and tuberculosis (Tb) infections was evaluated. The in vitro antileishmanial activity against promastigotes of Leishmania donovani revealed exceptional activities of compounds 3, 12 and 13, with IC50 values ranging from 10.23 ± 1.50 to 15.58 ± 1.67 μg/mL, which is better than the IC50 value of the standard drug pentostam of 500 μg/mL. The selectivity of the compounds towards Leishmania parasites was evaluated via ex vivo studies in Swiss albino mice. The efficiency of these compounds against Tb infection was then evaluated using the in vitro anti-Tb microplate Alamar Blue assay. Five compounds, 3, 7, 8, 9 and 12, showed MIC100 values against the Mycobacterium tuberculosis H37Rv strain at 25 μg/mL, and compound 20 yielded an MIC100 value of 50 μg/mL. Mol. modeling of these compounds highlighted interactions with binding sites of dihydrofolate reductase, pteridine reductase and thymidylate kinase, thus establishing the rationale of their pharmacol. activity against both pathogens, which is consistent with the in vitro results. From the above results, it is clear that compounds 3 and 12 are promising lead candidates for Leishmania and Mycobacterium infections and may be promising for coinfections.

Archiv der Pharmazie (Weinheim, Germany) published new progress about Cell viability. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Quality Control of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Beltran-Hortelano, Ivan published the artcileDesign and synthesis of Mannich base-type derivatives containing imidazole and benzimidazole as lead compounds for drug discovery in Chagas Disease, Quality Control of 1468-83-3, the main research area is synthesis Mannich base imidazole benzimidazole drug discovery Chagas disease; drug design treatment Chagas disease Mannich base; Benzimidazole; Chagas disease; Imidazole; Mannich bases; Neglected tropical diseases; Trypanosoma cruzi.

The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, the most important parasitic infection in Latin America. The only treatments currently available are nitro-derivative drugs that are characterized by high toxicity and limited efficacy. Therefore, there is an urgent need for more effective, less toxic therapeutic agents. We have previously identified the potential for Mannich base derivatives as novel inhibitors of this parasite. To further explore this family of compounds, we synthesized a panel of 69 new analogs, based on multi-parametric structure-activity relationships, which allowed optimization of both anti-parasitic activity, physicochem. parameters and ADME properties. Addnl., we optimized our in vitro screening approaches against all three developmental forms of the parasite, allowing us to discard the least effective and trypanostatic derivatives at an early stage. We ultimately identified derivative I, which demonstrated excellent trypanocidal properties, and a synergistic mode of action against trypomastigotes in combination with the reference drug benznidazole. Both its druggability and low-cost production make this derivative a promising candidate for the preclin., in vivo assays of the Chagas disease drug-discovery pipeline.

European Journal of Medicinal Chemistry published new progress about Chagas disease. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Quality Control of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Pua, Aileen published the artcileImproved detection of key odourants in Arabica coffee using gas chromatography-olfactometry in combination with low energy electron ionisation gas chromatography-quadrupole time-of-flight mass spectrometry, Application In Synthesis of 1468-83-3, the main research area is odorant Arabica coffee GC olfactometry electron ionization qTOF MS; AEDA; Coffee; GC-QTOF; Low energy EI; Volatiles.

Four Arabica coffees (Brazil, Colombia, Ethiopia, and Guatemala) yield highly variant odors, attesting to the complexities of coffee aroma that command advanced anal. tools. In this study, their volatiles were extracted using solvent-assisted flavor evaporation (SAFE) and headspace solid-phase microextraction (HS-SPME). Due to matrix complexity, some trace odorants were detected in SAFE extracts by aroma extract dilution anal. (AEDA) but remained difficult to quantify by gas chromatog.-mass spectrometry (GC-MS). This prompted the application of low energy electron ionization (EI) coupled with GC-quadrupole time-of-flight (GC-QTOF). Optimal low EI GC-QTOF parameters (EI energy: 15 eV, acquisition rate: 3 Hz) were applied to achieve improved mol. ion signal intensity and reproducibility (relative standard deviation < 10%) across five compounds, which resulted in good linearity (R2 ≥ 0.999) and lowered detection levels (e.g. 0.025 ± 0.005 ng/mL for 4-hydroxy-5-methyl-3(2H)-furanone). Therefore, this method potentially improves the measurement of trace odorants in complex matrixes by increasing specificity and sensitivity. Food Chemistry published new progress about Coffea arabica. 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

Davanagere, Haleshappa published the artcileInvestigation of structural, physical, linear, and nonlinear optical properties of two novel thiophene centred D-π-A type push-pull organic derivatives for nonlinear optical applications, Quality Control of 1468-83-3, the main research area is phys linear nonlinear optical thiophene centered organic derivative.

The aim of the present study is to investigate the different key parameters of two novel thiophene based D-π-A type push-pull organic chalcone derivatives; 3-(4-nitrophenyl)- 3-hydroxy-1-(thiophen-2-yl) propan-1-one (2ATN) and 3-(4-nitrophenyl) -3-hydroxy -1-(thiophen-3-yl) propan-1-one (3ATN) through various exptl. techniques. The 2ATN and 3ATN single crystal are grown at ambient temperature by the slow evaporation solution growth technique. The single crystal X-ray diffraction anal. confirmed that both the title compounds 3ATN and 2ATN are crystallized in the triclinic crystal system under centrosym. structure with space group P-1. The 2ATN and 3ATN crystals are thermally stable up to 147.68°C and 197.4°C resp. The linear optical properties of grown crystals are characterized by photoluminescence and UV-visible spectroscopic technique. The Vicker’s microhardness test confirms the crystal’s hardness and the Vicker’s hardness number 19 kg/mm2 and 13 kg/mm2 of 2ATN and 3ATN resp., which are indicates the phys. stability of the crystals. The third-order nonlinear optical parameters are determined using Z-Scan technique under continuous wave laser source at 532 nm wavelength. Using the Kurtz-Perry method SHG efficiency was tested for both the crystals and the 3ATN crystal shows about 0.61 times the efficiency of urea crystal. The nitro substituted effects are described in the enhancement of NLO activity using structure-property relationship. The reported crystals can therefore be used for non-linear optical applications due to its excellent optical properties.

Journal of Molecular Structure published new progress about Crystal growth. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Quality Control of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Dayan, J. published the artcileApplication of the SOS chromotest to 10 pharmaceutical agents, Quality Control of 40180-04-9, the main research area is drug mutagenesis SOS chromotest assay.

The SOS function-inducing activity of 10 compounds belonging to different chem. classes was studied in Escherichia coli PQ37. The choice of these chems. was based on previously reported mutagenesis studies. This study indicated that 6 compounds which did not induce a pos. response in the Ames test and other mutagenesis tests were also neg. in the SOS chromotest. The other compounds studied had a pos. response in the SOS-inducing function in addition to the pos. results from the Ames test. In order to establish a correlation between these 2 tests a study requiring a larger selection of chem. agents is needed.

Mutation Research, Genetic Toxicology Testing published new progress about DNA SOS repair. 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

Orr, Suvi T. M. published the artcileMechanism-Based Inactivation (MBI) of Cytochrome P450 Enzymes: Structure-Activity Relationships and Discovery Strategies To Mitigate Drug-Drug Interaction Risks, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is cytochrome P450 enzyme inhibition drug interaction metabolism SAR.

The importance of mitigating drug-drug interaction (DDI) risks, which arise from inhibition of major human cytochrome P 450 enzymes is a well-established component of the lead optimization process in drug discovery. More recently, there has been much interest in clin. DDIs potentially arising via time- and concentration-dependent cytochrome P 450 inhibition, a phenomenon consistent with mechanism-based inactivation. Inactivated P 450 is catalytically incompetent and must be replenished by newly synthesized protein. Consequently, time-dependent inhibition of P450s presents a greater safety concern compared to reversible inhibition because of the increased propensity for pharmacokinetic interactions upon multiple dosing and the sustained duration of these interactions after discontinuation of the mechanism-based inactivator. Mechanism-based or time-dependent P 450 inhibitors pose an addnl. risk of idiosyncratic drug toxicity since the mechanism of time-dependency often involves the formation of reactive metabolites, which can react with proteins other than the P 450 isoenzyme responsible for catalysis. in vitro time-dependent inhibition (TDI) of P 450 enzymes is now routinely assessed as part of lead optimization efforts in preclin. drug discovery. However, identification of an in vitro TDI liability can raise several questions such as: What is the mechanism of TDI. Does it involve the formation of reactive metabolites. Is there a 1:1 correlation between P 450 TDI and RM formation (as measured from reactive metabolite trapping studies). What is the likelihood that a P 450 time-dependent inhibitor will also cause toxicity. What are the DDI risk mitigation options when dealing with P 450 inactivators in drug discovery – compound progression or termination. Several drugs exhibit in vitro TDI of P 450 enzymes, but only a fraction thereof causes clin. DDIs. Hence, when do we initiate labor-intensive medicinal chem. efforts to design compounds devoid of P 450 TDI liability. What are the best methods to precisely predict the likelihood of occurrence of clin. DDIs with drug candidates that inactivate P 450 enzymes. What are (if any) the qualifying considerations for clin. progression of a P 450 time-dependent inactivator with projected clin. DDI risks. In an effort to address these questions and hopefully provide answers to some of them, we embarked on the present venture wherein we highlight the current state-of-the-art knowledge in this field with a special emphasis on (a) available biochem. and mechanistic approaches in drug discovery to examine TDI of P 450 isoenzymes with new chem. entities, (b) structure-activity relationship studies with marketed drugs associated with DDIs via P 450 inactivation, (c) case studies of medicinal chem. tactics to abrogate P 450 inactivation liability, (d) strategies for progression of P 450 TDI-pos. drug candidates, and (e) the utility of in silico methodol., including the use of physiol.-based pharmacokinetic simulators, in drug discovery to predict the magnitude of clin. DDIs risks anticipated with new clin. candidates.

Journal of Medicinal Chemistry published new progress about Drug discovery. 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

Rana, Payal published the artcileDevelopment of a cell viability assay to assess drug metabolite structure-toxicity relationships, Category: benzothiophene, the main research area is drug metabolite toxicity assay cytochrome P 450 structure toxicity; Cytochrome P450; Drug-induced toxicity; Metabolic activation; Reactive metabolite; Structural alerts.

Many adverse drug reactions are caused by the cytochrome P 450 (CYP)-dependent activation of drugs into reactive metabolites. To reduce attrition due to metabolism-induced toxicity and to improve the safety of drug candidates, the authors developed a simple cell viability assay by combining a bioactivation system (human CYP3A4, CYP2D6 and CYP2C9) with Hep3B cells. The authors screened a series of drugs to explore structural motifs that may be responsible for CYP 450-dependent activation caused by reactive metabolite formation, which highlighted specific liabilities regarding certain phenols and anilines.

Bioorganic & Medicinal Chemistry Letters published new progress about Drug discovery. 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

Kakutani, Nobuyuki published the artcileNovel risk assessment of reactive metabolites from discovery to clinical stage, Application In Synthesis of 40180-04-9, the main research area is quetiapine rimonabant ritonavir hepatoprotectant drug discovery liver injury; Body burden; Cyanide; Cysteine; Hepatotoxicity; Reactive metabolites; Trapping assay.

This study was aimed to predict drug-induced liver injury caused by reactive metabolites. Reactive metabolites covalently bind to proteins and could result in severe outcomes in patients. However, the relation between the extent of covalent binding and clin. hepatotoxicity is still unclear. From a perspective of body burden (human in vivo exposure to reactive metabolites), we developed a risk assessment method in which reactive metabolite burden (RM burden), an index that could reflect the body burden associated with reactive metabolite exposure, is calculated using the extent of covalent binding, clin. dose, and human in vivo clearance. The relationship between RM burden and hepatotoxicity in humans was then investigated. The results indicated that this RM burden assessment exhibited good predictability for sensitivity and specificity, and drugs with over 10 mg/day RM burden have high-risk for hepatotoxicity. Furthermore, a quant. trapping assay using radiolabeled trapping agents ([35S]cysteine and [14C]KCN) was also developed, to detect reactive metabolite formation in the early drug discovery stage. RM burden calculated using this assay showed as good predictability as RM burden calculated using conventional time- and cost-consuming covalent binding assays. These results indicated that the combination of RM burden and our trapping assay would be a good risk assessment method for reactive metabolites from the drug discovery stage.

Journal of Toxicological Sciences published new progress about Drug discovery. 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, Application In Synthesis of 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem