Search results for "Chiral HPLC"

showing 4 items of 4 documents

Stereoselective Synthesis and Pharmacological Evaluation of 2,4-Bridged Piperidine Derivatives Designed to Activate the κ-Opioid Receptor

2021

endo-configurationdiastereoselective reductive aminationenantiomeric excessstructure-affinity relationshipNOESY spectrumKOR agonistconformational restrictionchiral HPLCSettore CHIM/08 - Chimica Farmaceutica2-azabicyclo[3.3.1]octanecis/trans configuration
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Novel σ1 antagonists designed for tumor therapy: Structure – activity relationships of aminoethyl substituted cyclohexanes

2021

Abstract Depending on the substitution pattern and stereochemistry, 1,3-dioxanes 1 with an aminoethyl moiety in 4-position represent potent σ1 receptor antagonists. In order to increase the stability, a cyclohexane ring first replaced the acetalic 1, 3-dioxane ring of 1. A large set of aminoethyl substituted cyclohexane derivatives was prepared in a six-step synthesis. All enantiomers and diastereomers were separated by chiral HPLC at the stage of the primary alcohol 7, and their absolute configuration was determined by CD spectroscopy. Neither the relative nor the absolute configuration had a large impact on the σ1 affinity. The highest σ1 affinity was found for cis-configured benzylamines…

DU145 tumor cellsCachannelPrimary alcohol01 natural sciencesAminoethylcyclohexanes; Antagonistic activity; Biotransformation; Ca; 2+; influx assay; Calculated free energy of binding; CD spectroscopy; Chiral HPLC; DU145 tumor cells; Inhibition of human prostate tumor cell growth; Lipophilicity; Molecular dynamics simulations; Molecular interactions; per-residue binding free energy; Selectivity; Stereochemistry; Structure affinity relationships; Voltage gated Ca; 2+; channel; σ receptors; σ; 1; receptor affinityInhibition of human prostate tumor cell growthStereochemistryDrug DiscoveryMoietySelectivityBiotransformationσ receptor0303 health sciencesChemistryAminoethylcyclohexanesCD spectroscopyAbsolute configurationAminoethylcyclohexaneMolecular interactionGeneral MedicineAntagonistic activityper-residue binding free energyreceptor affinityLipophilicityVoltage gated CaStereochemistry12+Calculated free energy of bindingRetinal ganglion03 medical and health sciencesσMolecular dynamics simulationChiral HPLCLipophilicityMolecular interactionsStructure affinity relationship030304 developmental biologyPharmacologyDU145 tumor cellinflux assayMolecular dynamics simulations010405 organic chemistryOrganic ChemistryDiastereomer0104 chemical sciencesChiral column chromatographyσ receptorsStructure affinity relationshipsEnantiomerEuropean Journal of Medicinal Chemistry
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Synthesis of 8-aminomorphans with high KOR affinity

2021

2-Azabicyclo[3.3.1]nonanes (morphans) with a (3,4-dichlorophenyl)acetyl group at 2-position and a pyrrolidino moiety at 8-position were designed as conformationally restricted analogs of piperidine-based KOR agonists. The synthesis started with 4-oxopiperidine-2-carboxylic acid comprising 13 reaction steps. At first the ketone 10 was transformed into diester 7 bearing a propionate side chain. Dieckmann condensation of diester 7 to afford bicyclic enolester 14 and subsequent Krapcho deethoxycarbonylation represent the key steps of the synthesis. The enantiomeric pyrrolidines (1S,5R,8R)-5a and (1R,5S,8S)-5a were separated by chiral HPLC. The eutomer (1S,5R,8R)-5a showed high KOR affinity (K-i…

Diastereoselective reductive aminationEnantiomeric excessStructure-affinity relationshipsPharmacologyPyrrolidinesReceptors Opioid kappaNOESY spectrumOrganic ChemistryMolecular ConformationStereoisomerismGeneral MedicineKOR agonistsEndo-configurationStructure-Activity RelationshipKOR pharmacophoreConformational restrictionChiral HPLCDihedral angleDrug DiscoveryCis/trans-configurationMorphan2-azabicyclo[3.3.1]nonaneEuropean Journal of Medicinal Chemistry
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Characterization of the synthetic cannabinoid MDMB-CHMCZCA

2016

The synthetic cannabinoid MDMB-CHMCZCA was characterized by various spectroscopic techniques including NMR spectroscopy and tandem mass spectrometry. The synthetic sample was found to be of S-configuration by VCD spectroscopy and comparison of the data with DFT calculations, while ECD spectroscopy was found to be inconclusive in this case. The enantiomeric purity of samples from test purchases and police seizures was assessed by a self-developed chiral HPLC method.

medicine.medical_treatmentNPS010402 general chemistryTandem mass spectrometry01 natural sciencesFull Research Paperlcsh:QD241-441lcsh:Organic chemistrymedicinelcsh:Sciencechiral HPLCSpectroscopyChromatographyChemistry010401 analytical chemistryOrganic ChemistryNuclear magnetic resonance spectroscopy0104 chemical sciencesCharacterization (materials science)Chiral column chromatographyChemistryVCD spectroscopyECD spectroscopylcsh:QCannabinoidEnantiomersynthetic cannabinoidsBeilstein Journal of Organic Chemistry
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