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US 5,491,159 AGranted
2-(3,5-di-tert-butyl-4-hydroxy-phenyl)-oxazoles as anti-atherosclerotic agents
AssigneeAmerican Home Products Corporation
InventorMichael S. Malamas
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AssigneeAmerican Home Products Corporation
InventorMichael S. Malamas
Estimating the term…
The earliest lesion of atherosclerosis is development of the fatty streak lesions which contain lipid-laden macrophages and lipid-laden smooth muscle cells. Macrophages do not take up native low density lipoprotein (LDL) but do take up modified, i.e., acetylated LDL or oxidized LDL via acetyl-LDL or "scavenger" receptors to form the foam cells of atherosclerotic plaque. Arterial smooth muscle cells generate superoxide and oxidize LDL in the presence of micromolar concentrations of Cu.sup.+2 or Fe.sup.+2. The way LDL can be modified by endothelial cells can be mimicked in vitro by incubation of the lipoprotein in the presence of CuCl.sub.2. The compounds of this invention inhibit copper mediated oxidation of LDL in vitro and are thus useful in the prophylaxis and treatment of clinical conditions for which inhibition of the oxidative modification of lipids is indicated, for example, atherosclerosis. The compounds of this invention are represented by the formula 1 below ##STR1## wherein: R.sup.1 is hydrogen, C.sub.1 -C.sub.6 alkyl, phenyl or naphthyl; R.sup.2 is OH, NH.sub.2, OR.sup.3, or NHCO.sub.2 R.sup.4 wherein R.sup.3 and R.sup.4 are independently selected from C.sub.1 -C.sub.6 alkyl, phenyl or naphthyl; or a pharmaceutically acceptable salt thereof.
A compound having the formula:
A method of inhibiting oxidative modification of low density lipoprotein which comprises administration to a mammal in need thereof a therapeutically effective amount of a compound having the formula:
A method for treating atherosclerosis which comprises administration to a mammal in need thereof a therapeutically effective amount of a compound of the formula:
A pharmaceutical composition which comprises a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of the formula:
Dependencies are inferred from the claim text.