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Complementary synthetic approaches to constitutionally diverse N-aminoalkylated isoindolinones: Application to the synthesis of falipamil and 5-HT1A receptor ligand analogues

Different synthetic approaches for the elaboration of poly and diversely substituted isoindolinones tailed with constitutionally diverse aminoalkylated chains have been developed. The key step is based upon the preliminary assembly of the isoindolinone template equipped with hydroxyalkyl appendages. Subsequent manipulation of the terminal hydroxy functionality afforded the targeted compounds and the synthetic utility of these approaches has been emphasized by the synthesis of the bradycardic agent falipamil and 5-HT1A receptor ligand analogues. Georg Thieme Verlag Stuttgart.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H772NO – PubChem

 

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The dihydrofuran template approach to furofuran synthesis

Flash vacuum pyrrolysis of vinyl epoxides provides cis-dihydrofuran carboxylic esters in good yields and diastereoselectivities, which, on base-promoted epimerisation afford the complementary trans series. The compounds provide a viable template for a Lewis acid promoted cyclisation to provide the 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane core found in the furofuran series of natural lignans. This strategy is stereodivergent and can be controlled to provide the exo-exo, exo-endo or endo-endo stereochemistries. The approach has been exemplified in syntheses of the sesamyl furofurans (¡À)-epiasarinin and (¡À)-asarinin. The Royal Society of Chemistry 2006.

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Palladium-catalyzed hydroacyloxylation of ynamides

In the presence of substoichiometric Pd(OAc)2, carboxylic acids undergo highly regio- and stereoselective additions to ynamides to provide alpha-acyloxyenamides.

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Oxazolidine | C3H1010NO – PubChem

 

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TERAHYDROBENZAZEPINES AS ANTAGONISTS AND/OR REVERSE AGONISTS OF THE HISTAMINE H3 RECEPTOR

The present invention relates to novel benzazepine derivatives 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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Synthesis of Nitrogen-Containing Goniothalamin Analogues with Higher Cytotoxic Activity and Selectivity against Cancer Cells

Two series of racemic goniothalamin analogues displaying nitrogen-containing groups were designed and synthesized. A total of 19 novel analogues were evaluated against a panel of four different cancer cell lines, along with the normal prostate cell line PNT2 to determine their selectivity. Among them, goniothalamin chloroacrylamide 13 e displayed the lowest IC50 values for both MCF-7 (0.5 mum) and PC3 (0.3 mum) cells, about 26-fold more potent than goniothalamin (1). Besides its higher potency, compound 13 e also displayed much higher selectivity than goniothalamin. In contrast, goniothalamin isobutyramide 13 c was the most potent analogue against Caco-2 cells (IC50=0.8 mum), about 10-fold more potent and 17-fold more selective than 1. These results reveal the potential of compounds 13 c and 13 e for further in vivo studies, representing the first goniothalamin analogues with IC50 values in the low micromolar range and high selectivity against MCF-7, Caco-2, and PC3 cancer cell lines.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H808NO – PubChem

 

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Phosphazene/triisobutylaluminum-promoted anionic ring-opening polymerization of 1,2-epoxybutane initiated by secondary carbamates

Attempts to use a carbamate-phosphazene base as the initiating system for the polymerization of 1,2-epoxybutane was unsuccessful. As a matter of fact, carbamate deprotonation by phosphazene bases led to their fast decomposition generating alkoxide anions which initiate the polymerization rather than carbamate anions. Conversely, in the presence of triisobutylaluminum-a Lewis acid-the in situ generation of an anionic initiator X- obtained by the deprotonation of the tBuP4 phosphazene base was tested as a possible way to initiate the polymerization of 1,2-epoxybutane. Particular attention was given to the detection of eventual transfer or side-reactions according to the carbamate:triisobutylaluminum:phosphazene base ratio, to the solvent dielectric constant and to the number of PN- units in the phosphazene base. The reaction was performed with a stoichiometric ratio (1::1:1) of carbamate:triisobutylaluminum:tBuP2, which gave the best results. Under these conditions, the initiation of the polymerization by the carbamate anion was quantitative; no transfer reactions have been observed and the polymerization proceeded in a controlled manner to afford amide end-capped poly(butylene oxide) with a narrow molar mass distribution and expected molar masses.

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In vitro antitumor evaluation of some new tetra substituted 1,2,4-triazines

A new series of tetra substituted 1,2,4-triazines (4, 5, 7 and 8) was synthesized via the reaction of 3,1-oxazolinone (1) with thiosemicarbazide to give 6-hydroxy-5-(p-hydroxybenzylidene)-3-phenyl-2-(amino) thioxo-1,2,4-triazine (3). Treatment of 1,2,4-triazine derivative 3 with carbon disulphide and p-chlorophenacyl bromide yielded the corresponding 1,2,4-triazine derivatives 4 and 7. Acetylation of tetra-substituted 1,2,4-tri-azines 4 and 7 with acetic anhydride gave tri acetyl and di acetyl derivatives 5 and 8. Compounds structure was confirmed by IR,1H,13C-NMR, MS, and elemental analysis. The cytotoxic activities of some synthesized, 1,2,4-triazines were evaluated on human hepatocellular carcinoma cells (HepG-2) and human colon carcinoma cells (HCT-116) using the MTT method. We found that, compounds 5 (IC50 = 3.60 mug/mL) and 8 (IC50 = 4.40 mug/mL) have better activity against HCT-116 cell line than the reference doxorubcin (IC50 = 5.30 mug/mL), while compound 7 has best activity against HepG-2 cell line.

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Decomposition of nitrosamines in aqueous monoethanolamine (MEA) and diethanolamine (DEA) solutions with UV-radiation

CO2 capture based on chemical absorption using amine solutions is considered to be the most feasible way to remove CO2 from low pressure sources. However, amines, when exposed to nitrous oxides, may form nitrosamines which are known to be carcinogenic. In this work the destruction of two nitrosamines, NDELA (nitrosodiethanolamine) and NDMA (nitroso-dimethylamine), with UV-light is studied in a batch reactor at room temperature and at 45C. Additionally, the effect of UV-light on the degradation of MEA is investigated.The results from this project clearly show that the rates of UV-induced decay of NDMA and NDELA are different. Additionally the efficiency of UV-light for decomposition of NDMA and NDELA depends on the type of solution. In dilute amine solutions (water wash solutions), the decay is much faster compared to more concentrated solutions. Colouring of the solutions, caused by degradation products, was found to decrease the effect of UV-light dramatically. A dynamic model for the reactor set-up used is developed and used for interpretation of the results. In all solutions the decay was found to be 1st order with respect to NDELA and NDMA concentrations.

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Reactions of 5-methylene-1,3-thiazolidine-2-thione and 5-methylene-2-oxazolidinone with isocyanates catalyzed by bases

5-Methylene-1,3-thiazolidine-2-thione and 5-methylene-2-oxazolidinone can react with isocyanates to give the corresponding condensed urethanes in high yields in the presence of organic or inorganic bases under mild reaction conditions.

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Oxazolidine – Wikipedia,
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Covalent modification of subtilisin Bacillus lentus Cysteine mutants with enantiomerically pure chiral auxiliaries causes remarkable changes in activity

Methanethiosulfonate reagents may be used to introduce virtually unlimited structural modifications in enzymes via reaction with the thiol group of cysteine. The covalent coupling of enantiomerically pure (R) and (S) chiral auxiliary methanethiosulfonate ligands to cysteine mutants of subtilisin Bacillus lentus induces spectacular changes in catalytic activity between diastereomeric enzymes. Amidase and esterase kinetic assays using a low substrate approximation were used to establish k(cat)/K(M) values for the chemically modified mutants, and up to 3-fold differences in activity were found between diastereomeric enzymes. Changing the length of the carbon chain linking the phenyl or benzyl oxazolidinone ligand to the mutant N62C by a methylene unit reverses which diastereomeric enzyme is more active. Similarly, changing from a phenyl to benzyl oxazolidinone ligand at S166C reverses which diastereomeric enzyme is more active. Chiral modifications at S166C and L217C give CMMs having both high esterase k(cat)/K(M)’s and high esterase to amidase ratios with large differences between diastereomeric enzymes. Copyright (C) 2000 Elsevier Science Ltd.

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Oxazolidine | C3H493NO – PubChem