Acenaphthyl-substituted guanidines and methods of use thereof

A method for treating or preventing nerve cell death comprising administering to a mammal exhibiting symptoms of nerve cell death or susceptible to nerve cell death an effective amount of a compound having the formula:

• ##STR27## wherein R is cycloalkyl of 3 to 12 carbon atoms, carbocyclic aryl, alkaryl, aralkyl or heterocyclic having 6 to 18 carbon atoms and containing 1-3 separate or fused rings, and 0-5 O, N and/or S ring atoms in an aryl, alicyclic or mixed ring system;
• R.sup.1 and R.sup.2 are the same or different and selected from the group consisting of hydrogen, lower C.sub.1-6 alkyl, lower C.sub.1-6 alkylamino, C.sub.5-10 aryl or substituted aryl;
• wherein R and the acenaphthyl group are optionally substituted by hydroxy, acetate, oxo, amino, lower C.sub.1-6 alkyl, lower C.sub.1-6 alkyl amino, alkoxy of 1-6 carbon atoms, di-lower C.sub.2-12 alkyl amino, nitro, azido, sulfhydryl, cyano, isocyanato, halogen, amido, sulfonato or carbamido.

A method for treating brain or spinal cord trauma, stroke or heart attack comprising administering to a mammal exhibiting symptoms of or susceptible to brain or spinal cord trauma, stroke or heart attack an effective amount of a compound having the formula:

• ##STR28## wherein R is cycloalkyl of 3 to 12 carbon atoms, carbocyclic aryl, alkaryl, aralkyl or heterocyclic having 6 to 18 carbon atoms and containing 1-3 separate or fused rings, and 0.5 O, N and/or S ring atoms in an aryl, alicyclic or mixed ring system;
• R.sup.1 and R.sup.2 are the same or different and selected from the group consisting of hydrogen, lower C.sub.1-6 alkyl, lower C.sub.1-6 alkylamino, C.sub.5-10 aryl or substituted aryl;
• wherein R and the acenaphthyl group are optionally substituted by hydroxy, acetate, oxo, amino, lower C.sub.1-6 alkyl, lower C.sub.1-6 alkyl amino, alkoxy of 1-6 carbon atoms, di-lower C.sub.2-12 alkyl amino, nitro, azido, sulfhydryl, cyano, isocyanato, halogen, amido, sulfonato or carbamido.

A method of treating a disease selected from the group consisting of Huntington's disease, Amyotrophic Lateral Sclerosis, Alzheimer's disease, Down's Syndrome, Korsakoff's disease, olivopontocerebellar atrophy, HIV-induced dementia, HIV-induced blindness, or multi-infarct dementia, the method comprising administering to a mammal exhibiting symptoms of said disease or susceptible to said disease an effective amount of a compound having the formula:

• ##STR29## wherein R is cycloalkyl of 3 to 12 carbon atoms, carbocyclic aryl, alkaryl, aralkyl or heterocyclic having 6 to 18 carbon atoms and containing 1-3 separate or fused rings, and 0-5 O, N and/or S-ring atoms in an aryl, alicyclic or mixed ring system;
• R.sup.1 and R.sup.2 are the same or different and selected from the group consisting of hydrogen, lower C.sub.1-6 alkyl, lower C.sub.1-6 alkylamino, C.sub.5-10 aryl or substituted aryl;
• wherein R and the acenaphthyl group are optionally substituted by hydroxy, acetate, oxo, amino, lower C.sub.1-6 alkyl, lower C.sub.1-6 alkyl amino, alkoxy of 1-6 carbon atoms, di-lower C.sub.2-12 alkyl amino, nitro, azido, sulfhydryl, cyano, isocyanato, halogen, amido, sulfonato or carbamido.