6533b827fe1ef96bd1285caf

RESEARCH PRODUCT

3,4-trans-4-Aryl-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolates—new group of potential cardiotonic drugs

Vida GaralieneR. VitolinaGunars DubursAivars KrauzeVija KlusaL. Sile

subject

ChronotropicCardiotonic AgentsPyridinesStereochemistryGuinea PigsBlood PressureCardiac activityIn Vitro TechniquesCardiotonic AgentsAldehydeChlorideChemical synthesischemistry.chemical_compoundHeart RateGroup (periodic table)Drug DiscoverymedicineAnimalsSulfhydryl CompoundsRats WistarPharmacologychemistry.chemical_classificationCardiotonic drugsArylOrganic ChemistryGeneral MedicineRatschemistryMilrinoneLead compoundMilrinonemedicine.drug

description

Abstract 3,4- trans -4-Aryl-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolates 6 – 11 were prepared by a Michael reaction of N -acetonylpyridinium chloride with 3-aryl-2-cyanothioacrylamides or by a one-pot three-carbon condensation of N -acetonylpyridinium chloride, aromatic aldehyde and 2-cyanothioacetamide, and their cardiotonic properties were studied. 3,4- trans -5-cyano-2-hydroxy-2-methyl-4-(3-nitrophenyl)-3-(1-pyridinio)-1,2,3,4-tetrahydropyridine-6-thiolate 8 was considered as a lead compound in this series since it in vitro experiments (spontaneously beating rat atria) showed a cardiotonic activity similar to that of milrinone 2 , however compound 8 induced activity at lover concentrations and without influence on chronotropic action of the heart. Unlike milrinone 2 , thiolate 8 in vivo experiments (anaesthetized rats) did not influence blood pressure and heart rate. The acute toxicity of compound 8 was more than 10 times lower than that of milrinone 2 .

yearjournalcountryeditionlanguage
2005-01-24European Journal of Medicinal Chemistry
https://doi.org/10.1016/j.ejmech.2005.04.004