Enantioselective syntheses and calcium channel modulating effects of (+)- and (-)-3-isopropyl 5-(4-methylphenethyll) 1,4-dihydro-2,6-dimethyl-4-(2-pyridyl)-3,5-pyridinedicarboxylates
| Autor: | Dean Vo, Michael W. Wolowyk, Edward E. Knaus, Carol-Anne McEwen, Nadeem Iqbal |
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| Rok vydání: | 1994 |
| Předmět: |
Magnetic Resonance Spectroscopy
Nifedipine Stereochemistry Guinea Pigs In Vitro Techniques Catalysis Analytical Chemistry Structure-Activity Relationship Drug Discovery medicine Animals Heart Atria Spectroscopy Pharmacology Voltage-dependent calcium channel Dose-Response Relationship Drug Molecular Structure Chemistry Calcium channel Organic Chemistry Dihydropyridine Antagonist Enantioselective synthesis Stereoisomerism Calcium Channel Blockers Myocardial Contraction Calcium Channel Agonists Knoevenagel condensation Enantiomer Isopropyl medicine.drug |
| Zdroj: | Chirality. 6(7) |
| ISSN: | 0899-0042 |
| Popis: | The (+)- and (−)-enantiomers of 3-isopropyl 5-(4-methylphenethyl) 1,4-dihydro-2,6-dimethyl-4-(2-pyridyl)-3,5-pyridinedicarboxylate were synthesized using an efficient highly enantioselective (ee ≥ 96%) variant of the Hantzsch dihydropyridine synthesis. The key step in this procedure involved the asymmetric Michael addition of a metalated chiral aminocrotonate, derived from D-valine or L-valine, respectively, to the Knoevenagel acceptor (Z)-2-isopropoxycarbonyl-1-(2-pyridyl)-but-1-en-3-one. Both enantiomers exhibited a dual cardioselective partial calcium channel agonist (positive inotropic)/smooth muscle selective calcium channel antagonist effect. The relative in vitro smooth muscle calcium channel antagonist activities of the (−):(+) enantiomers was 26:1. In contrast, the (+)-enantiomer exhibited a greater in vitro positive inotropic effect on guinea pig left atrium where the contractile force was maximally increased by 14.8% at a concentration of 1.63 × 10−8M. © 1994 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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