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In this review we chose to concentrate on the bibliography data from 2013 to 2015 (until February), related to the application of the Inverse Electron Demand Diels-Alder (IEDDA) reaction to the synthesis of heterocycles, as building blocks for natural products Moreover, the application of the IEDDA reaction to the recently developed bioorthogonal ligations (in 2008), using tetrazines moieties as the diene partners, and engineered alkenes or alkynes as dienophiles, will be detailed. The in vivo applications of the bioorthogonal liga-tions are particularly amazing and undoubtedly demonstrate the usefulness of this chemistry.

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New formaldehyde derivatives were prepared in good yields by a short and versatile route. Several crystal structures of corresponding thioacetic acid esters and thiols were determined. The thioacetates were cleaved under acidic or basic conditions affording the thiols in high yield, thus introducing the new substance classes of N-mercaptomethyl-alkylcarboxamides, N-mercapto- methylsulfonamides, and alkoxymethanethiols. Georg Thieme Verlag Stuttgart New York.

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This review presents a brief account of introduction of heterocyclic rings and carbohydrate appendages in peptide conjugates,and their effect on solution-phase self-assembling properties. Such scaffolds bring in geometrical considerations, metal binding sites and water solubility properties,for interesting applications of self-assembled soft matter.

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The present invention relates to benzazepine derivatives of formula ( I ) wherein: R1 represents -C3-7 cycloalkyl optionally substituted by C1-3 alkyl; having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders.

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Why Are Children Getting Addicted To (S)-4-Phenylthiazolidine-2-thione

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Taurine and structurally diverse substituted taurines have been synthesized by peroxyformic acid, oxidation of the thiazolidine-2-thione intermediates generated from, vicinal amino alcohols or aziridines and carbon disulfide. The stereochemistry and mechanisms of the reactions are disscussed. The method is a salt-free and versatile route, convenient in terms of purification, and can be used to synthesize optically active substituted taurines.

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This article is a brief review about the synthesis and chemistry of 2-cyanomethylene-4-thiazolidinone 1. The most significant applications of 4-thiazolidinone 1 in heterocyclic synthesis are due to its two reactive methylenes. The endo-cyclic methylene protons are activated by the neighboring carbonyl moiety and the exo-cyclic methylene protons by the adjacent cyano group. Different types of reactions, such as alkylation, coupling, and Knoevenagel condensation, as well as cyclization reactions are illustrated for the synthesis of different classes of biologically important heterocyclic skeletons from this novel precursor.

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Nocardiolactone was synthesized by using a Crimmins asymmetric aldolization followed by a DMAP-mediated removal of the auxiliary with concurrent protection of the carboxylic group as a benzyl ester, activation of the beta-hydroxyl group as a mesylate, hydrogenolysis of the benzyl ester, and a novel DBU-mediated lactonization that converted the syn-configuration to the trans one. Georg Thieme Verlag Stuttgart.

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Fungal infections have become ubiquitous diseases and their persistent nature and development of drug resistance have led to a global threat. Thereby urgent need to develop efficient antifungal agents is a must. Menace of protozoal diseases cannot be ruled out as the vaccines are not available currently and available anti-protozoal drugs are of low efficacy. Multidrug-resistant tuberculosis is responsible for the inefficient treatment of tuberculosis. Regarding cancer control, the five-membered heterocyclic compounds such as triazoles and tetrazoles are significant pharmacores that play prominent roles in drug design. In this regard, the research is being carried out in the field of drug design and synthesis considering azole-containing scaffolds as promising target molecules. In this review, the research on azoles having inhibitory properties against various disease causative factors such as fungi, protozoa, bacteria, mycobacteria, etc and various cancer cell lines is described. The whole research is classified on the basis of the type of the azole pharmacore on which the drug molecules are synthesized. The pharmacology of the designed molecules is expressed alongside emphasizing the moieties responsible for the potent activity. Besides, possible structural modification speculating higher biological properties is demonstrated based on SAR.

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Objective & Methodology: New hybrids of thiopyrimidine-five/six heterocyclic rings were synthesized and in vitro evaluated for their antiproliferative activity against three human cancer cell lines, namely HCT116 (human colorectal carcinoma), PC-3 (human prostate adenocarcinoma) and HepG2 (human liver carcinoma) cell lines. The most potency was elicited by the target candidates against the viability of HCT116 cell lines. It was higher than that obtained by the positive control 5-Fluorouracil (IC50 range; 0.11-0.49 muM, IC50, 5-FU; 1.10 muM). Results: Cell cycle analysis and apoptosis activation revealed that compound 20 induced G2/M phase arrest and apoptosis in HCT116 cells. In addition, compound 20 activates the caspases-9 and -3, a process which might mediate the apoptosis of HCT116 cells. Quantitative structure activity relationship study was done and revealed a high predictive power R2 suggesting goodness of the models. Conclusion: Furthermore, there is a good agreement between the observed pIC50 and the predicted pIC50 values, in addition, the low RMSD and standard error values indicate the accuracy of the model. Antimicrobial evaluation revealed that some of these compounds exhibited significant activities against the tested pathogenic bacteria and fungi, wherein compounds 7a, 14, 15a, 21a, produced the most potent and broad spectrum antibacterial and antifungal potency that was equivalent to that revealed by Vibramycin and Ketoconazole (MIC; 125 mug/mL). Moreover, compounds 15a, 21c, investigated dual potent antimicrobial and anticancer activity.

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We have recently observed that S-(2-hydroxyethylmercapto)-L-cysteine (L-CySSME), the mixed disulfide of L-cysteine and 2-mercaptoethanol, prevented cataracts induced in mice by acetaminophen (ACP) by functioning as a prodrug of L-cysteine and protecting the liver. This prompted the evaluation of the more lipophilic N-acetyl (Ac-CySSME) and ethyl ester (Et-CySSME) derivatives of L-CySSME as proprodrug forms, as well as the “D” enantiomer, as hepatoprotective agents. Serum ALT levels were measured at 24 hours after a toxic but nonlethal dose of ACP that insured 48 hour survival of the animals. Since the increases in ALT produced were highly variable (even after log transformation) and complicated the statistical analyses, we calculated confidence intervals for the mean ALT levels for each treatment group. This enabled comparisons to be made of the efficacy of L-CySSME as well as Ac-CySSME and Et-CySSME with other representative prodrugs of L-cysteine, namely, 2(RS)-methylthiazolidine-4(R)-carboxylic acid (MTCA), L-2-oxothiazolidine-4-carboxylic acid (OTCA), and N-acetyl-L-cysteine (NAC), in protecting the liver. It was shown that L-CySSME and MTCA administered intraperitoneally at 2.5 mmol/kg were superior to the other cysteine prodrugs at equimolar doses in protecting mice from hepatotoxicity elicited by a 400 mg/kg (2.65 mmol/kg) dose of ACP given i.p. 30 minutes prior to the prodrugs. The “D” form of CySSME was totally without protective effect. Oral doses of the prodrugs even at 2x the i.p. dose were less effective, although MTCA was the most protective.

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