Heterocyclic Building Blocks-Benzothiophene

Qin, Zemin published the artcileSynthesis of Substituted Pyrimido[1,2-b]indazoles through (3+2+1) Cyclization of 3-Aminoindazoles, Ketones, and N,N-Dimethylaminoethanol as One-Carbon Synthon, Synthetic Route of 1468-83-3, the main research area is pyrimidoindazole preparation; aminoindazole ketone dimethylaminoethanol three component cyclization.

The 2-mono- or 2,3-disubstituted pyrimido[1,2-b]indazoles I (R1 = Ph, thiophen-2-yl, naphth-2-yl, etc.; R2 = H, Me; R3 = H, 10-Br, 9-Br, 8-Br, etc.) are synthesized by a (3+2+1) three-component cyclization of 3-aminoindazoles II, ketones R1C(O)CH2R2 and N,N-dimethylaminoethanol as a methine source. The reaction demonstrates good tolerance of both aromatic and aliphatic ketones, as well as various substitution patterns in air.

Advanced Synthesis & Catalysis published new progress about Cyclization ((3+2+1)). 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Synthetic Route of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Hosey, Chelsea M. published the artcileBDDCS Predictions, Self-Correcting Aspects of BDDCS Assignments, BDDCS Assignment Corrections, and Classification for more than 175 Additional Drugs, Application In Synthesis of 40180-04-9, the main research area is afatinib alclofenac alpidem amifloxacin pharmacogenomics drug interaction toxicity; BDDCS; biopharmaceutics drug disposition classification system; disposition; drug development; drug transport.

The biopharmaceutics drug disposition classification system was developed in 2005 by Wu and Benet as a tool to predict metabolizing enzyme and drug transporter effects on drug disposition. The system was modified from the biopharmaceutics classification system and classifies drugs according to their extent of metabolism and their water solubility By 2010, Benet et al. had classified over 900 drugs. In this paper, we incorporate more than 175 drugs into the system and amend the classification of 13 drugs. We discuss current and addnl. applications of BDDCS, which include predicting drug-drug and endogenous substrate interactions, pharmacogenomic effects, food effects, elimination routes, central nervous system exposure, toxicity, and environmental impacts of drugs. When predictions and classes are not aligned, the system detects an error and is able to self-correct, generally indicating a problem with initial class assignment and/or measurements determining such assignments.

AAPS Journal published new progress about Biological permeation. 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

Zhuang, Shi-Yi published the artcileI2-DMSO mediated oxidative amidation of methyl ketones with anthranils for the synthesis of α-ketoamides, Recommanded Product: 3-Acetylthiophene, the main research area is formyl iodophenyl oxo arylacetamide preparation; aryl ethanone anthranil oxidative amidation iodine dimethyl sulfoxide mediated.

An I2-DMSO mediated oxidative amidation of Me ketones using anthranils as masked N-nucleophiles had been developed for the direct synthesis of α-ketoamides I [R1 = Ph, 4-MeC6H4, 4-MeOC6H4, etc.; R2 = 4-I, 4-MeO, 3-F-4-I, etc.] with high atom-economy. This metal-free process involved reductive N-O bond cleavage of anthranils and oxidative C-N bond formation of Me ketones under mild conditions. The iodo group and electrophilic formyl group provided multiple possibilities for further functionalization of α-ketoamides I.

Organic & Biomolecular Chemistry published new progress about Amidation (oxidative). 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

Bartoli, Ettore published the artcileUse, misuse and abuse of diuretics, Product Details of C13H8Cl2O4S, the main research area is review diuretics edema body fluid renal hemodynamics; Diuretics; Edema; Hyponatremia; Plasma volume; Renal failure; Renal pathophysiology.

Resolution of edema requires a correct interpretation of body fluids-related renal function, to excrete the excess volume while restoring systemic hemodynamics and avoiding renal failure. In heart failure, the intensive diuresis should be matched by continuous fluids refeeding from interstitium to plasma, avoiding central volume depletion. The slowly reabsorbed ascites cannot refeed this contracted volume in cirrhosis: the ensuing activation of intrathoracic receptors, attended by increased adrenergic and Renin release, causes more avid sodium retention, producing a pos. fluid and Na balance in the face of continuous treatment. High-dose-furosemide creates a defect in tubular Na causing diuresis adequate to excrete the daily water and electrolyte load in Chronic Renal Failure. Diuretic treatment requires care, caution and bedside “”tricks”” aimed at minimizing volume contraction by correctly assessing the homeostatic system of body fluids and related renal hemodynamics.

European Journal of Internal Medicine published new progress about Adrenoceptor agonists. 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

Minoletti, Claire published the artcileComparison of the Substrate Specificities of Human Liver Cytochrome P450s 2C9 and 2C18: Application to the Design of a Specific Substrate of CYP 2C18, Synthetic Route of 40180-04-9, the main research area is substrate specificity liver cytochrome P450 2C18; aroylthiophene P450 hydroxylation substrate preparation.

A series of 2-aroylthiophenes derived from tienilic acid by replacement of its OCH2COOH substituent with groups bearing various functions have been synthesized and studied as possible substrates of recombinant human liver cytochrome P450s 2C9 and 2C18 expressed in yeast. Whereas only compounds bearing a neg. charge acted as substrates of CYP 2C9 and were hydroxylated at position 5 of their thiophene ring at a significant rate, many neutral 2-aroylthiophenes were 5-hydroxylated by CYP 2C18 with kcat values of >2 min-1. Among the various compounds that were studied, those bearing an alc. function were the best CYP 2C18 substrates. One of them, compound 3, which bears a terminal O(CH2)3OH function, appeared to be a particularly good substrate of CYP 2C18. It was regioselectively hydroxylated by CYP 2C18 at position 5 of its thiophene ring with a KM value of 9 ± 1 μM and a kcat value of 125 ± 25 min-1, which are the highest described so far for a CYP 2C. A comparison of the oxidations of 3, by yeast-expressed CYP 1A1, 1A2, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, and 3A5, showed that only CYP 2C8, 2C18, and 2C19 were able to catalyze the 5-hydroxylation of 3. However, the catalytic efficiency of CYP 2C18 for that reaction was considerably higher (kcat/KM value being 3-4 orders of magnitude larger than those found for CYP 2C8 and 2C19). Several human P450s exhibited small activities for the oxidative O-dealkylation of 3. The four recombinant CYP 2Cs were the best catalysts for that reaction (kcat between 1 and 5 min-1) when compared to all the P450s that were tested, even though it is a minor reaction in the case of CYP 2C18. All these results show that compound 3 is a new, selective, and highly efficient substrate for CYP 2C18 that should be useful for the study of this P 450 in various organs and tissues. They also suggest some key differences between the active sites of CYP 2C9 and CYP 2C18 for substrate recognition.

Biochemistry published new progress about Hydroxylation, enzymic. 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

Lewis, David F. V. published the artcileQuantitative structure-activity relationships (QSARs) for substrates of human cytochromes P450 CYP2 family enzymes, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is QSAR human cytochrome P450 CYP2 family enzyme.

The results of quant. structure-activity relationship (QSAR) studies on substrates of human CYP2 family enzymes are reported, together with those of a small number of CYP2A6, CYP2C19 and CYP2D6 inhibitors. In general, there are good correlations (R=0.90-0.99) between binding affinity (based on Km or KD values) and various parameters relating to active site interactions such as hydrogen bonding and π-π stacking. There is also evidence for the role of compound lipophilicity (as determined by either log P or log D7.4 values) in overall substrate binding affinity, and this could reflect the desolvation energy involved in substrate interaction within the enzyme active site. It is possible to estimate the substrate binding energy for a given P 450 from a combination of energy terms relating to hydrogen bonding, π-π stacking, desolvation and loss in rotatable bond energy, which agree closely (R=0.98) with exptl. data based on either Km or KD values. Consequently, it is likely that active site interactions represent the major contributory factors to the overall binding affinities for human CYP2 family substrates and, therefore, their estimation is of potential importance for the development of new chem. entities (NCEs) as this can facilitate an assessment of likely metabolic clearance.

Toxicology in Vitro published new progress about Free energy of binding. 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

Pearson, R. M. published the artcileBiochemical and hematological changes induced by tienilic acid combined with propranolol in essential hypertension, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is tienilate propranolol essential hypertension.

In a double blind crossover trial, in which 16 patients with essential hypertension received placebo, tienilic acid (I) [40180-04-9] (250 mg/day), propranolol (II) [525-66-6] (80 mg twice daily), or I (250 mg/day) combined with II (80 mg twice daily), average blood pressure in the lying position was 169/98, 157/94, 159/90, and 142/86 mm Hg for placebo, I-, II-, and I combined with II-treated patients, resp. Thus, the effects of I and II on blood pressure were additive, and no interactions between I and II were observed I reduced serum water from 0.33 to 0.18 mmol/L and induced hypokalemia which was corrected by II. Basophil count and Hb were lower after I treatment than they had been at the start of the study.

Lancet published new progress about Essential hypertension. 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

Mansuy, Daniel published the artcileNew biological reactive intermediates. Metabolic activation of thiophene derivatives, Application of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is metabolic activation thiophene derivative review.

A review and discussion with 16 references Metabolic activation of tienilic acid and its isomer, metabolic oxidation of thiophene in vivo and in vitro, inactivation and alkylation of P 450 2C9 upon metabolic activation of tienilic acid, thiophene sulfoxides – a new class of reactive metabolites were discussed.

Advances in Experimental Medicine and Biology published new progress about Biochemical alkylation. 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 of 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Lewis, D. F. V. published the artcileOn the recognition of mammalian microsomal cytochrome P450 substrates and their characteristics. Towards the prediction of human P450 substrate specificity and metabolism, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is mammal microsome cytochrome P450 isoform substrate specificity metabolism.

The characteristics of mammalian microsomal P 450 xenobiotic substrates are described, particularly with reference to the major P 450 isoforms associated with drug metabolism in humans. It is further reported that a relatively small number of mol., electronic, and physico-chem. properties are required to discriminate between chems. that exhibit specificity for human P 450 isoforms: CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. Mol. templates of superimposed substrates are shown to be complementary with the putative active sites of the relevant enzymes, thus enabling a possible prediction of P 450 specificity from structure. Factors contributing to metabolic clearance and binding affinity are also discussed, and methods for their calculation are described.

Biochemical Pharmacology published new progress about Sodium channel blockers. 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

Mancy, Annah published the artcileThe Substrate Binding Site of Human Liver Cytochrome P450 2C9: An Approach Using Designed Tienilic Acid Derivatives and Molecular Modeling, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is cytochrome P450 2C9 tienilate derivative association.

Biochem. experiments, using the well-defined human liver CYP2C9 expressed in yeast, and mol. modeling techniques were used to derive a predictive model for substrates of CYP2C9. The ability of 10 2-aroylthiophenes related to tienilic acid to act as substrates for CYP2C9 was studied. Four of them were original compounds that were synthesized and completely characterized by several spectroscopic techniques. In these 10 compounds various chem. functions, such as ester, amide, alc., phenol, ether or tetrazole functions, replaced the OCH2COOH function of tienilic acid. Among them, only the derivatives containing an acidic function (carboxylic acids, phenol, and tetrazole whose pKas are 4.8, 6.3, and 3.8, resp.) underwent a 5-hydroxylation of their thiophene ring like tienilic acid. Despite their close structural analogy with tienilic acid, all of the other compounds not only did not undergo any 5-hydroxylation of their thiophene ring but also failed to act as inhibitors of CYP2C9. These results strongly suggested that the presence, at pH 7.4, of a neg. charge on the substrates is a very important feature in its recognition by CYP2C9. In fact, the four new substrates of CYP2C9 described in this study, a carboxylic acid, phenol, and tetrazole derivative, each of which is related to tienilic acid, and the antiinflammatory drug, suprofen (with Km between 12 and 130 μM and kcat between 0.2 and 1.3 min-1), as well as almost all CYP2C9 substrates reported in the literature, exhibit a pKa below 7 (except phenytoin whose pKa is 8.1). They mainly exist as anions at physiol. pH. By using mol. modeling techniques, 12 CYP2C9 substrates were superimposed with respect to their hydroxylation site and fitted onto templates, which were rigid mols. such as (S)-warfarin and phenytoin. It was thus possible to arrange them in order that all their anionic sites were at a distance around 4 Å from a common point (a putative cationic site of the protein) in space. These results provide a model of the substrate binding site of CYP2C9, in which substrates interact through their anionic site A- with a cationic residue of the CYP2C9 protein C+. In that model, the distance between the hydroxylation site (Hy) and the anionic site (A-) is 7.8 Å, and the ∠HyA-C+ angle is 82°.

Biochemistry published new progress about Enzyme functional sites. 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