Nifedipine type compounds

The reaction of ethyl acetoacetate, benzaldehyde, and urea leads to ethyl 1,2,3,4-tetrahydro-6-methyl-2-oxo-4-phenyl-5-pyrimidinecarboxylate. This reaction (the so called Biginelli reaction) was discovered over 100 years ago [93T6937], Interest in these dihydropyrimidines has increased rapidly mainly due to their close structural relationship to the pharmacologically important dihydropyridine calcium channel blockers of the nifedipine-type [93T6937], The dibromo (51) and monobromo derivatives (55) of the most simple Biginelli compounds mentioned above are readily obtained by bromination [93T6937], and the reactions of these derivatives with sodium azide have been studied recently [90LA505] [91 JCS(P1)1342],... 

Seidel W, Meyer H, Born L, Kazda K, Dompert W. Rigid calcium antagonists of the nifedipine type Geometrical requirements for the dihydropyridine receptor. In Seydel J, editor, QSAR and strategies in the design of bioactive compounds. Weinheim VCH, 1985. p. 366-9. 

The most common type of Ca channel in smooth muscle is the L-channel. It belongs, as do all known channels, to the same family of channels as the Na channel of nerve and skeletal muscle, and has a conductance of about 20pS. A cardinal characteristic of the L-channel is its affinity for and sensitivity to a number of dihydropyridine compounds. These drugs can affect the probability of L-chan-nels being open. The inhibitory members (e.g., nifedipine) of this group of drugs decrease the L-channel open-time probability, while the excitatory members, (e.g., BAY-K 8644), increase the open-time probability. The implication here is that the... 

In order to explore deeper insight into the mechanism of actions of DHPs, several authors carried out molecular modehng studies on these compounds [52-54]. In a recent molecular modeling study on calcium channel blockers, nifedipine and black mamba toxin FS2 (a venom of the black mamba snake, which has been demonstrated to block the L-type calcium channel [55,56], is a small peptide consisting of 58-74 amino acid residues and having 4-5 intramolecular disulfide bridges formed by cystein residues), Schleifer [54] observed the following ... 

Carbon-11 labelled calcium channel antagonists C-nifedipine, C-nisoldipine, C-nitrendipine and C-CFj-nifedipine possessing vasodilating and hypotensive properties have been synthesized using a modified Hantzsch-type cyclocondensation proce-dure . Condensation of aldehydes 242, 243 and 244 with 3-aminocrotonic acid esters 245, 246, 247 and with acetoacetic ester 248 produced in one pot after 12 hours reflux in dry ethanol the methyl sulphonylethyl protected dihydropyridines 249-252. Deprotection of the carboxylic acids by alkaline hydrolysis followed by conversion into the dihydropyridine monocarboxylic acids 253-256 gave potassium salts in situ, and subsequent methylation with CH3I produced the corresponding labelled title compounds 257-260 (equation 102),... 

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