Dihydropyrimidine calcium channel blockers: 2-heterosubstituted 4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines
Citations Over TimeTop 10% of 1990 papers
Abstract
2-Heterosubstituted-4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecar box ylic acid esters 8, which lack the potential CS symmetry of dihydropyridine calcium channel blockers, were prepared and evaluated for biological activity. Biological assays using potassium-depolarized rabbit aorta and radioligand binding techniques showed that some of these compounds are potent mimics of dihydropyridine calcium channel blockers. The combination of a branched ester (e.g. isopropyl, sec-butyl) and an alkylthio group (e.g. SMe) was found to be optimal for biological activity. When compared directly with similarly substituted 2-heteroalkyldihydropyridines 9, dihydropyrimidines 8 were found to be 30-fold less active. The solid-state structure of dihydropyrimidine analogue 8g shows that these compounds can adopt a molecular conformation which is similar to the reported conformation of dihydropyridine calcium channel blockers.
Related Papers
- → Worsening of rosacea in patients treated with dihydropyridine calcium channel blockers: a clinical observation(2011)13 cited
- → Discovery and evaluation of selective N-type calcium channel blockers: 6-Unsubstituted-1,4-dihydropyridine-5-carboxylic acid derivatives(2012)13 cited
- → Gene Activations of CYP2B1 and CYP3A1 by Dihydropyridine Calcium Channel Antagonists in the Rat Liver: the Structure-Activity Relationship(2004)7 cited
- → Drug Interactions of Dihydropyridine Calcium Channel Blockers (CCBs) involving CYP3A4 Enzymes(2019)1 cited
- → 3-Methyl 5-isopropyl 2-methoxyiminomethyl-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate(2001)