63675-72-9

Manufacturing Process

Boiling a solution of 12.7 g of 2'-nitrobenzylideneacetoacetic acid methyl ester and 7.1 g of β-amino-crotonic acid isopropyl ester in 50 ml of methanol for 10 hours yielded 2,6-dimethyl-4-(2'-nitrophenyl)-1,4-dihydropyridine-3,5- dicarboxylic acid 3-methyl ester-5-isopropyl ester of melting point 174°C (from ethanol). Yield 48% of theory.

Therapeutic Function

Coronary vasodilator

Biochem/physiol Actions

L-type (CaV1.2) calcium channel blocker; dihydropyridine-type calcium channel blocker with selectivity for smooth muscle (CaV1.2b) over cardiac muscle (CaV1.2a). Arterial vasodilator and antihypertensive agent.

Definition

ChEBI: A dihydropyridine that is 1,4-dihydropyridine which is substituted by methyl groups at positions 2 and 6, a methoxycarbonyl group at position 3, an o-nitrophenyl group at position 4, and an isobutoxycarbonyl group at position 5. The racemate, calcium channel blocker, is used in the treatment of hypertension and angina pectoris.

Brand name

Sular (Sciele);Baymycard.

General Description

In vitro studies show that the effects ofnisoldipine, 1,4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylic acid methyl 2-methylpropyl ester(Sular), on contractile processes are selective, with greaterpotency on vascular smooth muscle than on cardiac muscle.Nisoldipine is highly metabolized, with five majormetabolites identified. As with most of the dihydropyridines,the cytochrome P450 (CYP) 3A4 isozyme is mainlyresponsible for the metabolism of nisoldipine. The majorbiotransformation pathway appears to involve the hydroxylationof the isobutyl ester side chain. This particular metabolitehas approximately 10% of the activity of the parentcompound.