Search results for "DISCOVERY"

showing 10 items of 4119 documents

Synthesis and antiproliferative activity of 2'-O-allyl-1-beta-D-arabynofuranosyl-uracil, -cytosine and -adenine

1997

Abstract With the aim to design potential inhibitors of ribonucleotide reductase (RR), 2′-O-allyl-β-D-arabinofuranosyl-uracil ( 4 ), -cytosine ( 7 ) and -adenosine ( 10 ) were prepared and evaluated for their cytostatic activity against Molt4/C8, CEM and L1210 cell lines. Although our preliminary data do not allow to assess if RR is the intracellular target, the results point to differences in the (anti)metabolic behavior of these compounds. This study also offers a general synthesis of 2′-O-allyl-β-D-arabinofuranosyl nucleosides for potential applications in the preparation of 2′-O-allyl-β-D-oligoarabino nucleotides.

chemistry.chemical_classificationStereochemistryorganic chemicalsOrganic ChemistryClinical Biochemistryfood and beveragesPharmaceutical ScienceUracilBiological activityBiochemistryAdenosineChemical synthesischemistry.chemical_compoundRibonucleotide reductasechemistryBiochemistryDrug DiscoverymedicineMolecular MedicineNucleotideMolecular BiologyNucleosideCytosinemedicine.drug
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Effect of ionic liquid organizing ability and amine structure on the rate and mechanism of base induced elimination of 1,1,1-tribromo-2,2-bis(phenyl-…

2006

Abstract The kinetics of the elimination reaction of 1,1,1-tribromo-2,2-bis(phenyl-substituted)ethanes into the corresponding 1,1-dibromo-2,2-bis(phenyl-substituted)ethenes induced by amines were studied in three room temperature ionic liquids ([BMIM][BF 4 ], [BMIM][PF 6 ], [BdMIM][BF 4 ]). In order to have information about reagent–ionic liquid interactions, the reaction was carried out over the temperature range (293.1–313.1 K). To study the effect of the amine on the rate and occurrence of the elimination reaction, several primary, secondary and tertiary amines with different structure (cyclic and acyclic), basicity and steric requirements were used. The data collected show that the reac…

chemistry.chemical_classificationSteric effectsBase (chemistry)Organic ChemistryInorganic chemistryKineticsAtmospheric temperature rangeionic liquids elimination reaction base catalysisBiochemistryMedicinal chemistrychemistry.chemical_compoundElimination reactionchemistryDrug DiscoveryIonic liquidAmine gas treatingTetrahedron
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Carbonic anhydrase inhibitors

1999

Reaction of 20 aromatic/heterocyclic sulfonamides containing a free amino, imino, hydrazino or hydroxyl group, with 8-quinoline-sulfonyl chloride afforded a series of water-soluble (as hydrochloride or triflate salts) compounds. The new derivatives were assayed as inhibitors of the zinc enzyme carbonic anhydrase (CA), and more precisely of three of its isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form), involved in important physiological processes. Efficient inhibition was observed against all three isozymes, but especially against CA II (in nanomolar range), which is the isozyme known to play a critical role in aqueous humor secretion within the ciliary processes of the eye…

chemistry.chemical_classificationSulfonylbiologyChemistryHydrochlorideOrganic ChemistryClinical BiochemistryQuinolinePharmaceutical ScienceBiochemistryMedicinal chemistrySulfonamidechemistry.chemical_compoundDorzolamideEnzyme inhibitorCarbonic anhydraseDrug Discoverybiology.proteinmedicineMolecular MedicineMoietyOrganic chemistryMolecular Biologymedicine.drugBioorganic & Medicinal Chemistry
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Stereocontrolled solid-phase synthesis of fluorinated partially-modified retropeptides via tandem aza-Michael/enolate-protonation

2003

N-Acylation of Wang resin-bound l-α-amino acids with 2-trifluoromethyl-propenoyl chloride, followed by asymmetric tandem aza-Michael/enolate-protonation by a series of l-α-amino esters and final release from the resin, afforded a representative library of partially-modified retropeptides incorporating a stereodefined trifluoroalanine surrogate. The stereocontrol can be dramatically improved (up to 15:1) by using apolar solvents like carbon tetrachloride and DABCO as base.

chemistry.chemical_classificationTandemBase (chemistry)Organic ChemistryProtonationDABCOBiochemistryMedicinal chemistryChloridechemistry.chemical_compoundSolid-phase synthesischemistryDrug DiscoverymedicineOrganic chemistrymedicine.drugTetrahedron Letters
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Two New Acylated Tridesmosidic Saponins from Astragalus armatus

2010

Two new tridesmosidic glycosides of (3β,6α,16β,20R,24S)-20,24-epoxycycloartane-3,6,16,25-tetrol (=cycloastragenol), armatosides I and II (1 and 2, resp.), were isolated from the roots of Astragalus armatus (Fabaceae) as well as the known bidesmosidic glycosides of cycloastragenol, trigonoside II (3) and trojanoside H (4). Their structures were elucidated as (3β,6α,16β,20R,24S)-3-O-(2,3-di-O-acetyl-β-D-xylopyranosyl)-20,24-epoxy-25-O-β-D-glucopyranosyl-6-O-β-D-xylopyranosylcycloartane-3,6,16,25-tetrol (1), and (3β,6α,16β,20R,24S)-3-O-(2-O-acetyl-β-D-xylopyranosyl)-20,24-epoxy-25-O-β-D-glucopyranosyl-6-O-β-D-xylopyranosylcycloartane-3,6,16,25-tetrol (2). These structures were established by e…

chemistry.chemical_classificationTraditional medicineOrganic ChemistryGlycosideFabaceaeAstragalus armatusBiochemistryCatalysisInorganic Chemistrychemistry.chemical_compoundchemistryDrug DiscoveryCycloastragenolPhysical and Theoretical ChemistryHelvetica Chimica Acta
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Reaction of lithium enediolates with perfluoroketene dithioacetals. Synthesis of α-trifluoromethyl γ-dicarboxylic acid derivatives

2004

The reaction of perfluoroketene dithioacetals with dianions of carboxylic acids proceeds through the substitution of the vinylic fluoride. The preparative value of this reaction depends strongly on the reaction and work-up conditions, the optimisation of which led to use LDA as a base and multiple extraction techniques. The overall process may be considered as a formal synthesis of α-trifluoromethyl γ-dicarboxylic acid derivatives.

chemistry.chemical_classificationTrifluoromethylBase (chemistry)Organic ChemistryExtraction (chemistry)chemistry.chemical_elementBiochemistryMedicinal chemistrychemistry.chemical_compoundFormal synthesisDicarboxylic acidchemistryDrug DiscoveryOrganic chemistryLithiumFluorideTetrahedron Letters
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The role of the trifluoromethyl group in reactivity and selectivity in polar cycloaddition reactions. A DFT study

2012

Abstract The role of the trifluoromethyl group in reactivity, regio-, and stereoselectivity in cycloaddition reactions has been analyzed by studying the 1,3-dipolar cycloaddition (13DC) reactions of nitrone 4 with 3,3,3-trifluoro-1-nitropropene 7b and 3,3,3-trifluoro-2-nitropropene 14 using density functional theory (DFT) methods at the B3LYP/6-311G(d) level. The recent M06-2X functional has also been evaluated but, although the thermodynamic performance is improved, the kinetic data are not necessarily better than those obtained by the popular B3LYP functional for cycloaddition reactions. Four reactive channels associated with the meta and ortho regio- and endo and exo stereoselective appr…

chemistry.chemical_classificationTrifluoromethylChemistryStereochemistryOrganic ChemistryRegioselectivityBiochemistryCycloadditionNitronechemistry.chemical_compoundNitroethyleneDrug DiscoveryElectrophileStereoselectivityReactivity (chemistry)Tetrahedron
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Convenient High Yielding Gram Scale Solution Synthesis of Methionine-Enkephalin.

1998

A simple, large-scale synthesis of a cytokine, methionine-enkephalin, Tyr-Gly-Gly-Phe-Met, has been elaborated. Classical solution peptide chemistry methods without protection of amino acid side-chain functions and 1+(2+2) segment condensation were used. A nine-step synthesis from commercial amino acid derivatives was developed with yields ranging from 86% to 99%, averaging 92%. The purity of all intermediates was found to be 99.0-100% by HPLC. The process has been used to prepare greater than 150 g quantities of the pentapeptide as a monohydrate of 100% purity. Hydantoin formation was observed during saponification of Boc-Tyr-Gly-Gly-Phe-Met-OMe and minimised.

chemistry.chemical_classificationanimal structuresintegumentary systemChemistryHydantoinPeptideGeneral ChemistryGeneral MedicinePentapeptide repeatHigh-performance liquid chromatographyChemical synthesisAmino acidchemistry.chemical_compoundDrug DiscoveryPeptide synthesisOrganic chemistrySaponificationChemical and Pharmaceutical Bulletin
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Cycloartane Glycosides from Three Species of Astragalus (Fabaceae)

2011

Nine cycloartane-type glycosides were isolated from three species of the genus Astragalus (Fabaceae): From the aerial parts of A. cicer L., two new saponins, cicerosides A and B (1 and 2, resp.), i.e., a tetradesmosidic and tridesmosidic cycloartane-type glycosides besides one known compound, from the roots of A. sempervirensLam., one known saponin, and from the roots of A. ptilodesBoiss. var. cariensisBoiss., five known compounds. Their structures were established mainly by 600-MHz 2D-NMR techniques (1H,1H-COSY, TOCSY, NOESY, HSQC, and HMBC) and mass spectroscopy.

chemistry.chemical_classificationbiologyAstragalus speciesOrganic ChemistrySaponinGlycosideFabaceaebiology.organism_classificationBiochemistryCatalysisInorganic ChemistryAstragaluschemistryGenusDrug DiscoveryBotanyPhysical and Theoretical ChemistryTwo-dimensional nuclear magnetic resonance spectroscopyHelvetica Chimica Acta
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Influence of negative allosteric cooperativity in cation transport.

1992

Abstract The bis-macrocyclic ether5 seems to have a negative allosteric cooperativity and is able to transport double the amount of Na+ and K+ cations as monocyclic systems. This compound could be used as a simple model of the plasma membrane Na+−K+ ATPase which actively pumps Na+ out and K+ into the cell, respectively.

chemistry.chemical_classificationbiologyChemistryATPaseSodiumOrganic ChemistryAllosteric regulationInorganic chemistryIonophorechemistry.chemical_elementCooperativityBiochemistryCrystallographyMembraneDrug Discoverybiology.proteinCrown etherCation transportTetrahedron Letters
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