0000000000925926

AUTHOR

Thomas M Böhme

showing 2 related works from this author

Design and pharmacology of quinuclidine derivatives as M2-selective muscarinic receptor ligands

2001

In our search for M2-selective muscarinic receptor antagonists, we synthesized 1,3-disubstituted indenes. The effects of different basic moieties with regard to binding and selectivity towards the five distinct muscarinic receptor subtypes were investigated. The results show that the quinuclidine series afforded the most promising compounds in terms of both receptor affinity and M2-subtype selectivity.

QuinuclidinesTertiary amineStereochemistryClinical BiochemistryPharmaceutical ScienceIn Vitro TechniquesLigandsBiochemistryChemical synthesischemistry.chemical_compoundAlzheimer DiseaseDrug DiscoveryMuscarinic acetylcholine receptorHumansReceptorMolecular BiologyAcetylcholine receptorReceptor Muscarinic M2Bicyclic moleculeOrganic ChemistryReceptors MuscarinicchemistryMolecular MedicineRadiopharmaceuticalsSelectivityTomography Emission-ComputedQuinuclidineBioorganic & Medicinal Chemistry Letters
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Structure-activity relationships of dimethindene derivatives as new M2-selective muscarinic receptor antagonists.

2003

A series of 2,3-disubstituted indenes, which are analogues of the widely used histamine H(1) receptor antagonist dimethindene, have been synthesized and studied as muscarinic and histamine receptor antagonists. The affinities of these compounds for the five human muscarinic receptor subtypes (M(1)-M(5)) and for human histamine H(1) receptors were determined in radioligand binding studies using membranes from transfected Chinese hamster ovary (CHO) cells and [(3)H]N-methylscopolamine ([(3)H]NMS). The results demonstrate that the diisopropyl analogue 19 has a similar high affinity as (S)-dimethindene at M(2) receptors ((S)-dimethindene: pK(i) = 7.52; (-)-19: pK(i) = 7.37) with an improved sel…

Tertiary amineStereochemistrymedicine.drug_classCHO CellsMuscarinic AntagonistsRadioligand AssayStructure-Activity RelationshipCricetinaeDrug DiscoveryMuscarinic acetylcholine receptormedicineAnimalsDimethindeneHumansReceptors Histamine H1ReceptorAcetylcholine receptorReceptor Muscarinic M2DimethindeneChemistryAntagonistStereoisomerismReceptor antagonistReceptors MuscarinicRadioligand AssayIndenesMolecular MedicineJournal of medicinal chemistry
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