Search results for "Tosyl"
showing 10 items of 89 documents
The Reaction of 4-Amino-2-oxazolines with Isocyanates and Isothiocyanates. Synthesis and X-Ray Structures of Polysubstituted 2-Imidazolidinones, 1,3-…
2006
Abstract Reactions of 4-alkylamino-2-phenyl-2-oxazolines 1 with isocyanates and isothiocyanates provide unprecedented efficient and regioselective heterocycle–heterocycle transformations. Compounds 1 reacted rapidly with tosyl isocyanate yielding directly 3-alkyl-4-benzamido-1-tosyl-2-imidazolidinones 4 in almost quantitative yields. The corresponding ureido intermediates 2 were not isolable species. However, the reactions with non-sulfonylated isocyanates or isothiocyanates were slower, leading to the expected ureido and thioureido derivatives 5, which were easily and efficiently transformed to either polysubstituted 2-imino-1,3-oxazolidine or 2-imino-1,3-thiazolidine hydrochlorides 7, res…
Validation of Dissolution Testing with Biorelevant Media: An OrBiTo Study.
2017
Dissolution testing with biorelevant media has become widespread in the pharmaceutical industry as a means of better understanding how drugs and formulations behave in the gastrointestinal tract. Until now, however, there have been few attempts to gauge the reproducibility of results obtained with these methods. The aim of this study was to determine the interlaboratory reproducibility of biorelevant dissolution testing, using the paddle apparatus (USP 2). Thirteen industrial and three academic laboratories participated in this study. All laboratories were provided with standard protocols for running the tests: dissolution in FaSSGF to simulate release in the stomach, dissolution in a singl…
Mass Spectrometric Investigation of Noncovalent Complexation between a Tetratosylated Resorcarene and Alkyl Ammonium Ions
2004
Noncovalent complexation between tetratosylated tetraethyl resorcarene (1) and primary, secondary, and tertiary alkyl ammonium ions (mMe, dMe, tMe, mEt, dEt, tEt, dBu, and dHex) was studied by electrospray ionization Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry. Interactions of the noncovalent complexes were investigated by means of competition experiments, collision-induced dissociation (CID) experiments, ion-molecule reactions with tripropylamine and gas phase H/D-exchange reactions with deuteroammonia. Gas phase ion-molecule reactions gave especially valuable information about the structure and properties of the complexes. Resorcarene 1 formed relatively stable…
Pivotal advance: alpha-galactosylceramide induces protection against lipopolysaccharide-induced shock.
2007
Abstract α−galactosylceramide, a natural killer T cell ligand, and its synthetic homolog, KRN7000, consistently influence IFN-γ and TNF-α release, both mediators of LPS-induced shock. To modify the course of endotoxin shock, we injected KRN7000 at different time points of experimental systemic Shwartzman reaction. Mice treated with KRN7000 survived when it was injected within 2 h before and after LPS challenge. Mice survival was associated with low levels of T helper 1 (Th1) cytokines, such as IFN-γ and TNF-α. By contrast, protection from endotoxin shock was associated with an increase of T helper 2 (Th2) cytokines, like IL-4 and IL-10. A role of Th2 cytokines in counteracting LPS-induced s…
Prophylaxis of lipopolysaccharide-induced shock by α-galactosylceramide
2008
AbstractThe NKT cell ligand α-galactosylceramide and its synthetic homologue KRN7000 stimulate rapid and copious secretion of IFN-γ and TNF-α release, both of which are key mediators of LPS-induced shock. We showed that KRN7000, injected before or within 2 h after LPS challenge, was able to prevent endotoxic shock. KRN7000 induced survival when the mice were injected 6, 9, or 12 days before the first injection of LPS, and this protective effect was associated with reduction upon subsequent challenge in the levels of IFN-γ, TNF-α, MCP-1, and an increase of IL-10. Further analysis showed that the animals treated with KRN7000 prior to LPS challenge had lower numbers of F4/80+, NKT, and NK cell…
The influence of phase transitions in phosphatidylethanolamine models on the activity of violaxanthin de-epoxidase
2008
In the present study, the influence of the phospholipid phase state on the activity of the xanthophyll cycle enzyme violaxanthin de-epoxidase (VDE) was analyzed using different phosphatidylethanolamine species as model lipids. By using (31)P NMR spectroscopy, differential scanning calorimetry and temperature dependent enzyme assays, VDE activity could directly be related to the lipid structures the protein is associated with. Our results show that the gel (L beta) to liquid-crystalline (L alpha) phase transition in these single lipid component systems strongly enhances both the solubilization of the xanthophyll cycle pigment violaxanthin in the membrane and the activity of the VDE. This pha…
Synthesis and evaluation of 2-tosylamino and 2-tosyliminopyrimidine derivatives as inhibitors of some leukocyte functions
2003
Abstract We have studied the potential anti-inflammatory effects of 20 2-tosylamino and 2-tosyliminopyrimidine new derivatives in human neutrophils. We have evaluated their interference with some leukocyte functions and 5-lipoxygenase activity. All the compounds reduced neutrophil degranulation process at concentrations in the μM range. Besides, compounds with a phenolic substitution inhibited leukotriene B 4 biosynthesis in neutrophils and decreased the cell-free 5-lipoxygenase activity. This study demonstrates that 2-tosylamino and 2-tosyliminopyrimidine derivatives can reduce the activation of neutrophil cells which may have relevance for the modulation of the inflammatory response.
Galactosylated micelles for a ribavirin prodrug targeting to hepatocytes.
2013
Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-dl-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver…
A novel compound heterozygous mutation in GALC associated with adult-onset Krabbe disease: case report and literature review
2021
Krabbe disease (KD) is a rare autosomal recessive lipid storage leukodystrophy. It is caused by deficient enzyme activity resulting from mutations of the β-galactocerebrosidase (GALC) gene. KD is distinguished into subtypes based on the age of onset; these are early infantile, late infantile, juvenile, and adult-onset. We report a case of a 47-year-old Caucasian man with a 2-year history of muscle atrophy and weakness in both hands associated with pyramidal signs and mild spasticity in the lower limbs. An extensive work-up led this motor neuron disease-like disorder to be diagnosed as adult-onset KD. The patient was found to be compound heterozygous for two GALC mutations (p.G286D and p.Y49…
Conditions for the Enhancing Effect of Protease Inhibitors on the Concanavalin A Induced Thymidine Response of Murine Lymphocytes
1983
Incorporation of [<sup>3</sup>H]-thymidine – [<sup>3</sup>H]-TdR – into concanavalin A (Con A) stimulated murine splenocytes and thymocytes was found to be enhanced by addition of certain concentrations of phenyl-methyl-sulfonylfluoride (PMSF), di-isopropylfluorophosphate (DFP), N-α-tosyl-<i>L</i>-lysyl-<i>L</i>-chloromethylketone (TLCK), and soybean trypsin inhibitor (SBTI). No enhancement could be observed when mononuclear cells of the peripheral blood were used, and a medium enhancement when thymocytes were applied. Furthermore, no enhancing effect of the protease inhibitors (PI) on the Con A response of murine splenocytes could be observed…