NOVEL INDOLE-2-CARBOXAMIDE AND CYCLOALKENO[1,2-B]INDOLE DERIVATIVES, STRUCTURE-ACTIVITY-RELATIONSHIPS FOR HIGH INHIBITION OF HUMAN LDL PEROXIDATION

Series of indole-2-carboxamide and cycloalkeno[1,2-b]indole derivative s were synthesized and evaluated in order to determine the necessary s tructural requirements for a high inhibition of human LDL copper-induc ed peroxidation. Various modulations were systematically performed on the indole and cycloalkeno[1,2-b]indole nuclei as well as on the carbo xamide moiety. The best compounds (3c, 3e, 7c, 7f, 7h, 7g, and 7o) are between 5 and 30 times more active than probucol itself. Two of these compounds (3c and 70) were selected for complementary in vitro and in vivo investigations, which have shown additional properties of intere st for the treatment and the prevention of atherosclerosis injuries. C ompound 3e was found to have some antiinflammatory properties while co mpound 70 was proved to protect endothelial cells from the direct cyto toxicity of oxidized LDL with some additional calcium channel blocking properties.