Phosphonate derivatives and methods of use thereof in the treatment of Alzheimer's disease

1. An Amyloid Binding Alcohol Dehydrogenase (ABAD) inhibitor of Formula III, or a stereoisomer, tautomer, pharmaceutically acceptable salt, or prodrug thereof

wherein

X is S or O;

the dashed bonds are independently present or absent;

R 1 and R 2 are each independently a hydrogen, hydroxyl, halo, alkoxy, or methylcarboxylate group;

R 4 and R 6 are each independently a hydrogen or phosphonate group; and

R 5 is a substituted or unsubstituted aryl or heteroaryl group;

with the proviso that at least one of R 4 or R 6 is a phosphonate group having the structure —PO(OR 7 ) 2 , wherein each R 7 is independently a methyl or ethyl group.

2. A method for ameliorating or treating Alzheimer's Disease comprising administering to a subject in need thereof a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an Amyloid Binding Alcohol Dehydrogenase inhibitor having the structure of Formula II

wherein

X is S or O;

R 1 and R 2 are each independently a hydrogen, hydroxyl, halo, alkoxy, or methylcarboxylate group;

R 4 is a phosphonate group; and

R 5 is a substituted or unsubstituted aryl or heteroaryl group, wherein said substituted aryl comprises one or more substituents selected from the group of —NO 2 , —CN, —NH 2 , —COOH, —OH, —OCH 3 , —OCF 3 , —CONH 2 , -alkyl, -alkoxy or a methylcarboxylate group thereby ameliorating or treating the subject's Alzheimer's Disease.

3. A pharmaceutical composition comprising the ABAD inhibitor of claim 1 and a pharmaceutically acceptable carrier.

4. A method for inhibiting the activity of Amyloid Binding Alcohol Dehydrogenase (ABAD) comprising contacting ABAD with an inhibitor of claim 1 thereby inhibiting the activity of ABAD.

5. A method for ameliorating or treating Alzheimer's Disease comprising administering to a subject in need thereof the pharmaceutical composition of claim 3 thereby ameliorating or treating the subject's Alzheimer's Disease.