This invention relates to certain dihydropyridines which are pro-drugs of the calcium antagonist amlodipine, which is chemically known as 2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbo nyl-6-methyl-1,4-dihydropyridine (see EP-B-0089167), and to intermediates useful in the preparation of these pro-drugs.
Calcium antagonists reduce the movement of calcium into the cell and are thus able to delay or prevent the cardiac contracture which is believed to be caused by an accumulation of intracellular calcium under ischaemic conditions. Excessive calcium influx during ischaemia can have a number of additional adverse effects which would further compromise the ischaemic myocardium. These include less efficient use of oxygen for ATP production, activation of mitochondrial fatty acid oxidation and, possibly, promotion of cell necrosis. Thus calcium antagonists are useful in the treatment or prevention of a variety of cardiac conditions, such as angina pectoris, cardiac arrythmias, heart attacks and cardiac hypertrophy. Calcium antagonists also have vasodilator activity since they can inhibit calcium influx in cells of vascular tissue and are thus also useful as antihypertensive agents and for the treatment of coronary vasospasm.
USPTO Backgrounds
USPTO Backgrounds