Search results for "Pyrimidinones"
showing 10 items of 20 documents
Brugada syndrome induced by BRAF and MEK inhibitors in a melanoma patient.
2017
H2-antihistaminics. 20. Structure-activity relationships in H2-receptor antagonists containing a 4-pyrimidone moiety.
1984
In a series of 5,6-substituted 4- pyrimidones 1 a-v the H2-antihistaminic activity was determined (guinea-pig atrium) and lipophilicity data are given in form of Rmo -values. The influence of different substituents at position 5 or 6 of a pyrimidone moiety has been studied. Quantitative structure-activity analyses showed the importance of lipophilicity for drug activity. Additionally other physicochemical substituent-properties may play a major role.
Phospholipidosis and down-regulation of the PI3-K/PDK-1/Akt signalling pathway are vitamin E inhibitable events associated with 7-ketocholesterol-ind…
2007
International audience; Among the oxysterols accumulating in atherosclerotic plaque, 7-ketocholesterol (7KC) is a potent apoptotic inducer, which favours myelin figure formation and polar lipid accumulation. This investigation performed on U937 cells consisted in characterizing the myelin figure formation process; determining the effects of 7KC on the PI3-K/PDK-1/Akt signalling pathway; evaluating the activities of vitamin E (Vit-E) (α-tocopherol) on the formation of myelin figures and the PI3-K/PDK-1/Akt signalling pathway and assessing the effects of PI3-K inhibitors (LY-294002, 3-methyladenine) on the activity of Vit-E on cell death and polar lipid accumulation. The ultrastructural and b…
An overview on chemical structures as ΔF508-CFTR correctors
2019
Deletion of phenylalanine at position 508 (F508del) in the CFTR protein, is the most common mutation causing cystic fibrosis (CF). F508del causes misfolding and rapid degradation of CFTR protein a defect that can be targeted with pharmacological agents termed “correctors”. Correctors belong to various chemical classes but are generally small molecules based on nitrogen sulfur or oxygen heterocycles. The mechanism of action of correctors is generally unknown but there is experimental evidence that some of them can directly act on mutant CFTR improving folding and stability. Here we overview the characteristics of the various F508del correctors described so far to obtain indications on key ch…
Factors affecting the amount and the mode of merocyanine 540 binding to the membrane of human erythrocytes. A comparison with the binding to leukemia…
1995
Abstract In the presence of albumin Merocyanine 540 (MC540) exhibits a very limited binding to the outer surface of the membrane of normal erythrocytes, whereas pronounced binding is observed to leukemia cells. To find out whether this difference is due to differences in the composition or structural organization of the cell membrane we analyzed effects of a number of covalent and non-covalent perturbations of the red cell membrane on the binding and fluorescence characteristics of membrane-bound MC540. It is shown that exposure of the cells to cationic chlorpromazine, neuraminidase or photodynamic treatment with AlPcS 4 as sensitizer caused a limited increase (30–50%) of MC540 binding, tog…
Predicting 19F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase–Inhibitor Complex
2020
Abstract The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable 19F chemical‐shift predictions to deduce ligand‐binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the 19F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleepi…
Solvent-Enhanced Diastereo- and Regioselectivity in the PdII-Catalyzed Synthesis of Six- and Eight-Membered Heterocycles viacis-Aminopalladation
2009
The Pd(II)-catalyzed intramolecular oxidative cyclization of tosyl-protected cis- and trans-N-allyl-2-aminocyclohexanecarboxamides was examined, and efficient syntheses of cyclohexane-fused pyrimidin-4-ones and 1,5-diazocin-6-ones were developed. In the course of the research, a marked solvent effect was observed on both the regio- and diastereoselectivity. Additionally, a novel Pd(II)-mediated domino oxidation, oxidative amination reaction was discovered. Our experimental and theoretical findings suggest that the reactions proceed via a cis-aminopalladation mechanism.
A new strategy for the synthesis of fluorinated 3,4-dihydropyrimidinones
2009
A new family of 3,4-dihydropyrimidinones (DHPMs) bearing fluorinated substituents at C6 have been prepared from gem-difluorinated nitriles, alkyl 3-butenoates and iso(thio)cyanates. This novel Biginelli-type process relies on the gamma-addition of the ester-derived enolate to fluorinated nitriles. A tandem nucleophilic addition aza-Michael reaction sequence completes the synthetic process. (C) 2009 Elsevier B.V. All rights reserved.
H2-Antihistaminika, 18. Mitt. 5,6-Alkylsubstituierte 4-Pyrimidinone mit H2-antihistaminischer Wirkung
1984
5,6-Alkylsubstituierte 2-{2-[(5-Methyl-4-imidazolyl)-methylthio]-ethylamino}-4-pyrimidinone wurden dargestellt und auf ihre H2-antihistaminische Wirksamkeit untersucht. H2-Antihistaminics, XVIII: 5,6-Alkyl-4-pyrimidones with H2-Antihistaminic Activity 5,6-Alkyl-2-{2-[(5-methyl-4-imidazolyl)methylthio]ethylamino}-4- pyrimidones were prepared and tested for their H2-antihistaminic activities.
Chemoselective reactions of N1-methyl-2-hydroxy-3-methylamino-3-phenylpropanamide with electrophiles. Synthesis of chiral hexahydro-4-pyrimidinones a…
2002
Abstract The reactivity of (2S,3S)-N1-methyl-2-hydroxy-3-methylamino-3-phenylpropanamide 1 , containing three nucleophilic centres has been studied against dihaloalkanes and aldehydes. Hexahydro-4-pyrimidinones or oxazolidines were obtained chemoselectively. Experimental results were explained by ‘ab initio’ calculations.