Heterocyclic Building Blocks-Benzothiophene

Matsunaga, Norikazu published the artcileAnalysis of the metabolic pathway of bosentan and of the cytotoxicity of bosentan metabolites based on a quantitative modeling of metabolism and transport in sandwich-cultured human hepatocytes, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is bosentan cytotoxicity metabolism transport hepatocyte.

To quant. understand the events in the human liver, we modeled a hepatic disposition of bosentan and its three known metabolites (Ro 48-5033, Ro 47-8634, and Ro 64-1056) in sandwich cultured human hepatocytes based on the known metabolic pathway. In addition, the hepatotoxicity of Ro 47-8634 and Ro 64-1056 was investigated because bosentan is well known as a hepatotoxic drug. A model illustrating the hepatic disposition of bosentan and its three metabolites suggested the presence of a novel metabolic pathway(s) from the three metabolites. By performing in vitro metabolism studies on human liver microsomes, a novel metabolite (M4) was identified in Ro 47-8634 metabolism, and its structure was determined Moreover, by incorporating the metabolic pathway of Ro 47-8634 to M4 into the model, the hepatic disposition of bosentan and its three metabolites was successfully estimated In hepatocyte toxicity studies, the cell viability of human hepatocytes decreased after exposure to Ro 47-8634, and the observed hepatotoxicity was diminished by pretreatment with tienilic acid (CYP2C9-specific inactivator). Pretreatment with 1-aminobenzotriazole (broad cytochrome P 450 inactivator) also tended to maintain the cell viability. Furthermore, Ro 64-1056 showed hepatotoxicity in a concentration dependent manner. These results suggest that Ro 64-1056 is directly involved in bosentan-induced liver injury partly because CYP2C9 specifically mediates hydroxylation of the t-Bu group of Ro 47-8634. Our findings demonstrate the usefulness of a quant. modeling of hepatic disposition of drugs and metabolites in sandwich cultured hepatocytes. In addition, the newly identified metabolic pathway may be an alternative route that can avoid Ro 64-1056- induced liver injury.

Drug Metabolism & Disposition published new progress about Anxiety disorders. 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, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Ames, Richard P. published the artcileAntihypertensive therapy and the risk of coronary heart disease, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is antihypertensive therapy heart disease health; health hazard antihypertensive.

Diuretic drugs, when used in the treatment of hypertension in patients caused an increase in the serum concentration of total cholesterol and triglycerides. High d. lipoprotein (HDL) cholesterol remains stable with thiazide-type diuretic drugs. Treatment with furosemide  [54-31-9], spironolactone  [52-01-7], reserpine  [50-55-5], and methyldopa  [555-30-6] does not affect serum total cholesterol or triglyceride concentrations However, methyldopa decreases HDL cholesterol, and furosemide increases the ratio of total to HDL cholesterol. When reserpine, methyldopa, or β-blocking drugs are added to diuretic therapy, triglyceride increases and HDL cholesterol decreases. The mechanism of the lipid-lipoprotein alterations is unknown, but the changes correlate with changes in glycoHb and serum glucose noted during diuretic-based therapy. The changes in total cholesterol and HDL cholesterol caused by some antihypertensive agents counterbalance the benefits on the development of coronary heart disease (CHD) expected from the control of blood pressure. Thus, treatment regimens with a more favorable influence on serum lipids may be crucial to better control of CHD. Apparently therapy which does not disturb glucose metabolism is likely to be free of lipid effect, and, therefore, would qualify as preferred therapy for hypertension.

Journal of Cardiovascular Pharmacology published new progress about Antihypertensives. 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, Name: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Roberts, C. J. C. published the artcileComparison of natriuretic, uricosuric, and antihypertensive properties of tienilic acid, bendrofluazide, and spironolactone, Recommanded Product: 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, the main research area is diuretic tienilate uricosuric antihypertensive; urate blood tienilate diuretic.

In a double-blind cross-over study, 13 previously untreated hypertensive patients were treated orally for 30 days with tienilic acid (I) [40180-04-9], bendrofluazide (II) [73-48-3], or spironolactone (III) [52-01-7], 250, 5, and 100 mg resp.; II caused the greatest natriuresis on the first treatment day, and the most rapid fall in blood pressure. The ultimate antihypertensive effects of I, II, and III were similar. I caused a reduction in serum urate concentrations, and rise in urate clearance, but II and III caused slight urate retention. I and II caused decreases, and III caused an increase in plasma K concentration No untoward effects were observed from I, II, or III. I is thus a moderately potent diuretic which lowers plasma urate concentrations and may be the drug of first choice for hypertensive patients who either already have gout, or are likely to develop it when taking thiazide diuretics.

British Medical Journal published new progress about Antihypertensives. 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

Yonetani, Yukio published the artcileHyperuricemia induced by some antihypertensives and uricosuric drugs in oxonate-treated rats, Application In Synthesis of 40180-04-9, the main research area is antihypertensive uricosuric hyperuricemia pharmacol model.

The effects of antihypertensive and uricosuric drugs were studied on plasma and urinary levels of uric acid [69-93-2] in K oxonate [2207-75-2]-treated rats. Animals with a catheterized aorta were used to successively collect blood samples and this procedure simplified the evaluation of progressive changes of plasma uric acid, under successive loading with K oxonate. The plasma uric acid level of the oxonate-treated rats was increased even with a single administration of diuretic chlorothiazides, furosemide [54-31-9] and diazoxide [364-98-7], and also uricosuric drugs such as tienilic acid [40180-04-9] and probenecid [57-66-9]. A well-maintained plasma uric acid level was also produced by exogenously administered uric acid in rats given allopurinol and K oxonate. Diazoxide, tienilic acid, and probenecid increased the plasma uric acid, whereas diuretic chlorothiazides did not. Furosemide tended to decrease the plasma uric acid level at the early stage of administration in rats treated with allopurinol [315-30-0], oxonate, and uric acid, but increased these levels several hours later when the effect was studied by uric acid loading with rats treated with allopurinol and oxonate. These effects also appeared as changes in the urine-excreted uric acid. Thus, the oxonate-treated rats demonstrated an acutely induced hyperuricemia not only with certain antihypertensives, but also with uricosuric drugs. The utility of these procedures for evaluating the hyperuricemic and uricosuric effects of drugs is discussed.

Japanese Journal of Pharmacology published new progress about Antihypertensives. 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

Cusi, Daniele published the artcileThe effect of tienilic acid on sodium(1+) and potassium(1+) transport in human red cells, HPLC of Formula: 40180-04-9, the main research area is tienilate sodium potassium erythrocyte.

The effect of tienilic acid (I) [40180-04-9] and other antihypertensive drugs with diuretic properties on Na+ and K+ transport in human red cells was investigated. I is a less efficient inhibitor of erythrocyte Na+, K+ cotransport than furosemide [54-31-9], as well as being a weaker diuretic. In addition, the thiazides and K+-sparing diuretics do not inhibit the Na+,K+-cotransport system. Under conditions in which the erythrocytes have all of their saturable Na+ and K+ transport systems blocked, the addition of I increases K+ permeability. This effect shows saturation kinetics with the increase in the internal K+ concentration and could not be blocked by specific inhibitors of K+ channels. Thus, I may affect the opening of transient or permanent K+ channels.

Molecular Pharmacology published new progress about Antihypertensives. 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, HPLC of Formula: 40180-04-9.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Shiradkar, Mahendra Ramesh published the artcileA novel approach to cyclin-dependent kinase 5/p25 inhibitors: A potential treatment for Alzheimer’s disease, Product Details of C13H8Cl2O4S, the main research area is thienyl triazole derivative preparation structure cyclin dependent kinase inhibitor.

Based on the earlier results of the inhouse database and compound library, a series of novel clubbed thienyl triazoles was designed which may emerge as potential cdk5/p25 inhibitors, for the treatment of Alzheimer’s disease. A benign synthesis was planned so as to take an advantage of MAOS (Microwave Assisted Organic Synthesis) method. Evaluation of the SAR of this series has allowed the identification of compounds 4, 5, 7 and 8 from series I while 13, 14, 16 and 17 from series II as significant cdk5/p25 inhibitors and thus have potential as possible treatments for Alzheimer’s disease.

Bioorganic & Medicinal Chemistry published new progress about Alzheimer disease. 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

Secci, Daniela published the artcile4-(3-Nitrophenyl)thiazol-2-ylhydrazone derivatives as antioxidants and selective hMAO-B inhibitors: synthesis, biological activity and computational analysis, Category: benzothiophene, the main research area is nitrophenylthiazolyl hydrazone synthesis antioxidant monoamine oxidase neurodegenerative disorder; (Thiazol-2-yl)hydrazone derivatives; Alzheimer’s disease; Parkinson’s disease; antioxidants; inhibitor; molecular modelling; monoamine oxidase; selective.

A new series of 4-(3-nitrophenyl)thiazol-2-ylhydrazone derivatives were designed, synthesized, and evaluated to assess their inhibitory effect on the human monoamine oxidase (hMAO) A and B isoforms. Different (un)substituted (hetero)aromatic substituents were linked to N1 of the hydrazone in order to establish robust structure-activity relationships. The results of the biol. testing demonstrated that the presence of the hydrazothiazole nucleus bearing at C4 a Ph ring functionalised at the meta position with a nitro group represents an important pharmacophoric feature to obtain selective and reversible human MAO-B inhibition for the treatment of neurodegenerative disorders. In addition, the most potent and selective MAO-B inhibitors were evaluated in silico as potential cholinesterase (AChE/BuChE) inhibitors and in vitro for antioxidant activities. The results obtained from mol. modeling studies provided insight into the multiple interactions and structural requirements for the reported MAO inhibitory properties.

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about Alzheimer disease. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Category: benzothiophene.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Celebioglu, Hasan Ufuk published the artcileCytotoxic effects, carbonic anhydrase isoenzymes, α-glycosidase and acetylcholinesterase inhibitory properties, and molecular docking studies of heteroatom-containing sulfonyl hydrazone derivatives, Computed Properties of 1468-83-3, the main research area is sulfonylhydrazone antitumor carbonic anhydrase glycosidase acetylcholinesterase inhibition mol docking; Heteroatom; antibacterial; anticancer; docking; enzyme inhibition; sulfonyl hydrazone.

Today, interest in studies on the search for new drugs to be used in diseases such as cancer, cardiovascular diseases, neurodegenerative diseases and diabetes, as well as prevention of microbial inflammation is increasing day by day. Emerging biol. and pharmacol. effects of sulfonyl hydrazone derivative compounds reveal their importance. In the present study, heteroatom-containing sulfonyl hydrazone derivatives have been studied for their anticancer and antimicrobial properties, as well as their effects on enzymes that could play roles in Alzheimer′s disease and diabetes. High doses of the tested compounds significantly decreased the cell viabilities of breast cancer (MCF-7) and prostate cancer (PC-3) cell lines. Furthermore, all compounds possessed antimicrobial activities against very common bacteria E. coli and S. aureus. These compounds were good inhibitors of the α-glycosidase, human carbonic anhydrase I and II isoforms and acetylcholinesterase enzyme with Ki values in the range of 1.14 ± 0.14-3.63 ± 0.26 nM for α-glycosidase, 66.05 ± 9.21-125.45 ± 11.54 nM for hCA I, 89.14 ± 10.43-170.22 ± 26.05 nM for hCA II and 754.03 ± 73.22-943.92 ± 58.15 nM for AChE, resp. Mol. docking method was used to theor. compare biol. activities of sulfonyl hydrazone derivatives against enzymes. The theor. results were compared with the exptl. results. Thus, these compounds have strong biol. activities.

Journal of Biomolecular Structure and Dynamics published new progress about Alzheimer disease. 1468-83-3 belongs to class benzothiophene, name is 3-Acetylthiophene, and the molecular formula is C6H6OS, Computed Properties of 1468-83-3.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Mitsumori, Susumu published the artcileSynthesis and Biological Activity of Various Derivatives of a Novel Class of Potent, Selective, and Orally Active Prostaglandin D2 Receptor Antagonists. 2. 6,6-Dimethylbicyclo[3.1.1]heptane Derivatives, Formula: C9H10O2S, the main research area is dimethylbicycloheptane prostaglandin derivative preparation; prostaglandin D2 receptor antagonist bicycloheptane skeleton preparation; antiallergenic dimethylbicycloheptane prostaglandin derivative preparation.

Novel prostaglandin D2 (PGD2) receptor antagonists having the bicyclo[2.2.1]heptane ring system as a prostaglandin skeleton are a potent new class of antiallergic agents and suppressed various allergic inflammatory responses such as those observed in conjunctivitis and asthma models. In the present study, PGD2 receptor antagonists having the 6,6-dimethylbicyclo[3.1.1]heptane ring system were synthesized. These derivatives have the amide moiety, in contrast to those with the bicyclo[2.2.1]heptane ring system, which have the sulfonamide group. The derivatives having the 6,6-dimethylbicyclo[3.1.1]heptane ring also exhibited strong activity in PGD2 receptor binding and cAMP formation assays. In in vivo assays such as allergic rhinitis, conjunctivitis, and asthma models, these series of derivatives showed excellent pharmacol. profiles. In particular, compound I also effectively suppressed eosinophil infiltration in allergic rhinitis and asthma models. This compound (I, S-5751) is now being developed as a promising alternative antiallergic drug candidate.

Journal of Medicinal Chemistry published new progress about Allergic rhinitis. 19156-54-8 belongs to class benzothiophene, name is 4,5,6,7-Tetrahydrobenzo[b]thiophene-3-carboxylic acid, and the molecular formula is C9H10O2S, Formula: C9H10O2S.

Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

Battula, Satyanarayana published the artcileAccessing Grignard Reluctant Aldehyde in 2-Oxoaldehyde by Organocuprates to Give [1,2] Addition and Oxidative Coupling Reactions, Synthetic Route of 1468-83-3, the main research area is dione preparation; oxoaldehyde preparation Grignard reagent addition and oxidative coupling reaction; ketone hydrolysis.

Novel finding of aldehyde in 2-oxoaldehyde (2OA) is presented as it unprecedentedly disinclines to react with Grignard reagents but reacts with moderate organocuprate reagents in anaerobic condition to give [1,2] addition (α-hydroxyketones) reaction. In the presence of air, the reaction produces an efficient protocol for the synthesis of 1,2-diones through a copper-catalyzed oxidative cross-coupling reaction at room temperature Mechanistic studies indicate that α-hydroxy ketone perhaps is generated before the hydrolysis step/acid work-up process. The α-keto group of 2OA causes to exhibit this peculiar aldehyde behavior toward these organometallic reagents.

ACS Omega published new progress about Addition reaction. 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