A. Fassihi, Carlos A. Velázquez, E. Knaus
Mar 1, 2004
Citations
0
Influential Citations
5
Citations
Journal
Journal of Heterocyclic Chemistry
Abstract
The Hantzsch condensation of 5-formyluracil (1) with methyl, isopropyl or isobutyl acetoacetate (2a-c) in the presence of ammonium hydroxide afforded the respective dialkyl 1,4-dihydro-2,6-dimethyl-4-(2,4-dloxo-1,2,3,4,-tetrahydropyrimidin-5-yl)pyridine-3,5-dicarboxylate (3a-c). A group of alkyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)pyridine-5-carboxylates (6a-c) were also prepared using a modified Hantzsch reaction that involved the condensation of 5-formyluracil with nitroacetone and either methyl, isopropyl or isobutyl 3-aminocrotonate (5a-c). A C-4 2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl substituent is not a suitable bioisostere for the traditional C-4 aryl or heteroaryl substituents present in 1,4-dihydropyridine calcium channel modulators since diisopropyl 1,4-dihydro-2,6-dimemyl-4-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)pyridine-3,5-dicarboxylate (3b) and isobutyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2,4-dloxo-1,2,3,4-tetrahydropyrimidin-5-yl)pyridine-5-carboxylate (6c) did not exhibit any in vitro calcium channel antagonist activity using a guinea pig smooth muscle calcium channel antagonist assay, or a guinea pig left atrium calcium channel agonist (positive inotropic) assay.