Search results for "Antagonistic activity"

showing 2 items of 2 documents

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
researchProduct

Synthesis and Structure-Affinity Relationships of Spirocyclic Benzopyrans with Exocyclic Amino Moiety

2019

σ1 and/or σ2 receptors play a crucial role in pathological conditions such as pain, neurodegenerative disorders, and cancer. A set of spirocyclic cyclohexanes with diverse O-heterocycles and amino moieties (general structure III) was prepared and pharmacologically evaluated. In structure-activity relationships studies, the σ1 receptor affinity and σ1:σ2 selectivity were correlated with the stereochemistry, the kind and substitution pattern of the O-heterocycle, and the substituents at the exocyclic amino moiety. cis-configured 2-benzopyran cis-11b bearing a methoxy group and a tertiary cyclohexylmethylamino moiety showed the highest σ1 affinity ( Ki = 1.9 nM) of this series of compounds. In…

synthesisexocyclic amino moietyReceptors Opioid mudocking studieCrystallography X-RayLigands01 natural sciencesopioid receptorschemistry.chemical_compoundProtein structureDrug DiscoveryMoiety0303 health sciencesσ1 receptor ligandsstructure (σ1) affinity relationshipmolecular dynamicBenzyl groupMolecular MedicinesynthesiBenzopyransSelectivityHydrophobic and Hydrophilic Interactionsfree binding enthalpyStereochemistrychange of receptor profileMolecular Dynamics Simulation03 medical and health sciencesStructure-Activity Relationshipσ1 receptor ligands; spirocyclic compounds; benzopyrans; benzofurans; exocyclic amino moiety; synthesis; structure (σ1) affinity relationships; σ1 antagonistic activity; receptor selectivity; molecular dynamics; docking studies; free binding enthalpy; X-ray crystal structure; opioid receptors; MOR affinity; change of receptor profile; structure MOR affinity relationshipsstructure (σ1) affinity relationshipsStructure–activity relationshipHumansReceptors sigmaBenzopyransSpiro Compoundsspirocyclic compoundBinding siteMOR affinity030304 developmental biologybenzopyranbenzofuransσ1 receptor ligandBinding Sitesspirocyclic compoundsreceptor selectivitystructure MOR affinity relationshipsdocking studiesbenzofuranopioid receptorX-ray crystal structuremolecular dynamics0104 chemical sciencesProtein Structure Tertiary010404 medicinal & biomolecular chemistrychemistrySalt bridgeσ1 antagonistic activity
researchProduct