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Bioactive thiazole and benzothiazole derivatives

The heterocycles are the versatile compounds existing in almost all natural products and synthetic organic compounds, usually associated with one or the other biological activity. Among the heterocycles the thiazoles and benzothiazoles occupy a prominent position. They possess a broad range of biological activities and are foundin many potent biologically active molecules and drugs such as vitamin thiamine, sulfathiazol (antimicrobial drug), ritonavir (antiretroviral drug), abafungin (antifungal drug) and tiazofurin (antineoplastic drug). The thiazole moiety is abundantly found in natural products while benzothiazole moiety is rare. In this review we disclose the literature reports of thiazoles and benzothiazoles possessing different biological activities.

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Reference:
Quinuclidine – Wikipedia,
Quinuclidine | C7H430N | ChemSpider

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Synthesis of new beta-lactams bearing the biologically important morpholine ring and POM analyses of their antimicrobial and antimalarial activities

Some new beta-lactams bearing biologically important morpholine ring have been synthesized by acylation of amino beta-lactams in the presence of morpholine-4-carbonyl chloride. These novel beta-lactams were prepared under mild reaction conditions without any solvent in short reaction times. Their biological activities have been examined against microbial agents such as Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) and fungi such as Candida albicans (C. albicans) and Candida glabrata (C. glabrata). They have been also tested against Plasmodium falciparum K14 resistant strain and showed moderate to good IC50 values.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H327N | ChemSpider

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Children learn through play, and they learn more than adults might expect. Science experiments are a great way to spark their curiosity, get their minds active, and encourage them to do something that doesn’t involve a screen. Recommanded Product: 2682-49-7, C3H5NOS. A document type is Article, introducing its new discovery., Recommanded Product: 2682-49-7

Hydrogen Bonding. Part 7. A Scale of Solute Hydrogen-bond Acidity based on log K Values for Complexation in Tetrachloromethane

A scale of solute hydrogen-bond acidity has been constructed using equilibrium constants (as log K values) for complexation of series of acids (i) against a given base in dilute solution in tetrachloromethane, equation (A). Forty-five such equations have been solved to yield LB and DB log Ki = LB log KAHi +DB (A) values characterising the base, and log KAH values that characterise the acid. In this analysis, use has been made of the novel observation that all the lines in equation (A) intersect at a given point where log K = log KAH = -1.1 with K on the molar scale. Some 190 log KAH values that constitute a reasonably general scale of solute hydrogen-bond acidity have been obtained. It is shown that there is no general connection between log KAH and any proton-transfer quantities, although certain family dependences are obtained. A number of acid-base combinations are excluded from equation (A), and alternative log KAHE values have been determined for such cases. The general log KAH values may be transformed into alpha2H values suitable for use in multiple linear-regression analysis through the equation alpha2H = (log KAH +1 .1 )/4.636.

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Quinuclidine – Wikipedia,
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Two small molecules restore stability to a subpopulation of the cystic fibrosis transmembrane conductance regulator with the predominant disease-causing mutation

Cystic fibrosis (CF) is caused by mutations that disrupt the plasma membrane expression, stability, and function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat CF, although some studies suggest that they have counteracting effects on CFTR stability. Here, we investigated the impact of these compounds on the instability of F508del-CFTR, the most common CF mutation. To study individual CFTR Cl- channels, we performed single-channel recording, whereas to assess entire CFTR populations, we used purified CFTR proteins and macroscopicCFTRCl-currents. At 37 C, low temperature-rescued F508del-CFTR more rapidly lost function in cell-free membrane patches and showed altered channel gating and current flow through open channels. Compared with purified wildtype CFTR, the full-length F508del-CFTR was about 10 C less thermostable. Lumacaftor partially stabilized purified fulllength F508del-CFTR and slightly delayed deactivation of individual F508del-CFTR Cl- channels. By contrast, ivacaftor further destabilized full-length F508del-CFTR and accelerated channel deactivation. Chronic (prolonged) co-incubation of F508del-CFTR-expressing cells with lumacaftor and ivacaftor deactivated macroscopic F508del-CFTR Cl- currents. However, at the single-channel level, chronic co-incubation greatly increased F508del-CFTR channel activity and temporal stability in most, but not all, cell-free membrane patches. We conclude that chronic lumacaftor and ivacaftor co-treatment restores stability in a small subpopulation of F508del-CFTR Cl- channels but that the majority remain destabilized. A fuller understanding of these effects and the characterization of the small F508del-CFTR subpopulation might be crucial for CF therapy development.

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Quinuclidine – Wikipedia,
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Prodrugs and conjugates of thiol-and selenol-containing compounds and methods of use thereof

Disclosed is a prodrugs of the formula: 1 where A is a sulfur or a selenium, and R is derived from a mono- di- or oligo- saccharide.Also disclosed is a prodrug of the formulas; 2 where A is sulfur or selenium, R? is derived from a sugar and R? has the formula (CHOH)nCH2OH, where n is 1 to 5, or R? is an alkyl or aryl group, orR? is ?O, and the R? groups may be the same or different and may be hydrogen, alkyl, alkoxy, carboxy.Also disclosed is a conjugate of an antioxidant vitamin and a thiolamine or selenolamine.Also disclosed is a prodrug of the formula; 3 where A is sulfur or selenium, and R? is derived from a sugar and R? has the formula (CHOH)nCH2OH, where n is 1 to 5, or R? is also be an alkyl or aryl group, orR? is ?O, and R?is an alkoxy, or an amine group.Also disclosed is a prodrug of the formula: 4 R is COOH or H, and R? is derived from a sugar and R? has the formula (CHOH)nCH2OH, where n is 1 to 5, or R? is an alkyl or aryl group, orR? is ?O.[From equivalent US6841536] Disclosed is a prodrug of the formula: [image] where A is a sulfur or a selenium, and R is derived from a mono- di- or oligo- saccharide.Also disclosed is a prodrug of the formula: [image] where A is sulfur or selenium, R? is derived from a sugar and R? has the formula (CHOH)nCH2OH, where n is 1 to 5, or R? is an alkyl or aryl group, or R? is ?O, and the R? groups may be the same or different and may be hydrogen, alkyl, alkoxy, carboxy.Also disclosed is a conjugate of an antioxidant vitamin and a thiolamine or selenolamine.Also disclosed is a prodrug of the formula; [image] where A is sulfur or selenium, and R? is derived from a sugar and R? has the formula (CHOH)nCH2OH, where n is 1 to 5, or R? is also be an alkyl or aryl group, or R? is ?O, and R? is an alkoxy, or an amine group.Also disclosed is a prodrug of the formula: [image] where R is COOH or H, and R? is derived from a sugar and R? has the formula (CHOH)nCH2OH,where n is 1 to 5, or R? is an alkyl or aryl group, or R? is ?O.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H188N | ChemSpider

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Synthesis of various fused heterocyclic rings from thiazolopyridine and their pharmacological and antimicrobial evaluations

Various fused-heterocyclic-derivatives containing thiazolopyridine moieties has been synthesized by allowing 5-aminothiazolo[3,2-a]pyridine derivative 1 to undergo annulations reactions with different reagents under different-reaction conditions. The biological assessment of compounds 2, 11, 14, 15, and 19 showed remarkable antimicrobial activities. In addition, selected derivatives of the products were screened for their anticancer activities against two tumor cell lines using MTT assay and the results showed that some of these compounds have potent cytotoxic effect, as concluded from their IC50 values. Meanwhile, compounds 3a, 7 have exhibited very strong potency as anticancer candidates. Thiazolopyridine structures have been confirmed as a useful lead compounds for the development of new anticancer agents. Molecular docking showed that,-some of the synthesized compounds more suitable inhibitor against-ALR2 with farther alteration in future.

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Quinuclidine – Wikipedia,
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The recent progress of isoxazole in medicinal chemistry

Isoxazole compounds exhibit a wide spectrum of targets and broad biological activities. Developing compounds with heterocycle rings has been one of the trends. The integration of isoxazole ring can offer improved physical-chemical properties. Because of the unique profiles, isoxazole ring becomes a popular moiety in compounds design. In this review article, the major focus has been paid to the applications of isoxazole compounds in treating multiple diseases, including anticancer, antimicrobial, anti-inflammatory, etc. Strategies for compounds design for preclinical, clinical, and FDA approved drugs were discussed. Also, the emphasis has been addressed to the future perspectives and trend for the application.

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Quinuclidine – Wikipedia,
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Concise and Additive-Free Click Reactions between Amines and CF3SO3CF3

Trifluoromethyl trifluoromethanesulfonate has proved to be an excellent reservoir of difluorophosgene and a promising click ligation for amines in the preparation of urea derivatives, heterocycles, and carbamoyl fluorides under metal- and additive-free conditions. The reactions are rapid, efficient, selective, and versatile, and can be performed in benign solvents, giving products in excellent yields with minimal efforts for purification. The characteristics of the reactions meet the requirements of a click reaction. The use of trifluoromethyl trifluoromethanesulfonate as a click reagent is advantageous over other ?CO? sources (e.g., TsOCF3, PhCO2CF3, CsOCF3, AgOCF3, and triphosgene) because this reagent is readily accessible; easy to scale up; and highly reactive, even under metal- and additive-free conditions. It is anticipated that CF3SO3CF3 will be increasingly as important as SO2F2 as a click agent in future drug design and development.

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Quinuclidine – Wikipedia,
Quinuclidine | C7H459N | ChemSpider

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In silico study directed towards identification of novel high-affinity inhibitors targeting an oncogenic protein: BRD4-BD1

Bromodomain-containing protein 4 (BRD4) is a member of the bromodomain and extra-terminal domain (BET) family of proteins. It epigentically regulates the transcription of growth-promoting genes and has become an attractive target for the development of anticancer and anti-inflammatory agents. In the current study, we performed an in silico screening of a small-molecule chemical library against the acetyl?lysine binding site of the first bromodomain (BD1) in BRD4 protein. Potential inhibitors identified through virtual screening were further studied through molecular dynamics simulations, water entrapment analysis and Molecular Mechanics (MM)/Poisson?Boltzmann surface area (PBSA) binding free energy calculations. Many of the identified compounds exhibit better G-score (?11.64 kcal?mol?1 to ?10.31 kcal?mol?1) and predicted binding affinity (?9.66 kcal?mol?1 to ?6.63 kcal?mol?1) values towards BRD4-BD1 than that of the reference compound (+)-JQ1. Molecular dynamics simulation studies show that in free-form BRD4 the reported conserved water molecules are not retained at their specific positoins due to flexibiliy in the ZA-loop. In BRD4?ligand complexes the number and positions of conserved water molecules depends on the bound ligand. Identified potential inhibitors bind stably at the acetyl?lysine binding pocket of BRD4 and form direct and water-mediated hydrogen bonds with higher occupancy which may contribute to ligand specificity towards BRD4-BD1. Further, through MM/PBSA we calculated the binding free energies of selected compounds, which shows that they have comparable energies to that of (+)-JQ1, while NSC744713 shows better binding free energy.

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Quinuclidine – Wikipedia,
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Synthesis of pyrazoline-thiazolidinone hybrids with trypanocidal activity

A series of novel 4-thiazolidinoneepyrazoline conjugates have been synthesized and tested for anti-Trypanosoma brucei activity. Screening data allowed us to identify five thiazolidinoneepyrazoline hybrids, which possess promising trypanocidal activity, with IC50 <1.2 muM. The highest active thiazolidinoneepyrazoline conjugates 3c and 6b (IC50 values of 0.6 mM and 0.7 mM, respectively) were 6-times more potent antitrypanosomal agents than nifurtimox. In addition, these compounds, as well as 6d and 6e had selectivity index higher than 50, and were more selective than nifurtimox. SAR study included substituent variations at the pyrazoline moiety, modifications of N3 position of the thiazolidinone portion, elongation of the linker between the heterocycles, as well as rhodanineeisorhodanine isomerism. It was also shown that methyl or aryl substitution at the thiazolidinone N3-position is crucial for trypanocidal activity. Because enzymes can increase reaction rates by enormous factors and tend to be very specific, SDS of cas: 2682-49-7, typically producing only a single product in quantitative yield, they are the focus of active research.you can also check out more blogs about SDS of cas: 2682-49-7

Reference:
Quinuclidine – Wikipedia,
Quinuclidine | C7H309N | ChemSpider