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(4, 5, 6, 7-tetrahydro-1-H-indol-7-yl) acetic acid derivatives for treatment of Alzheimer's disease

Abstract:

Statistical Manual of Mental Disorders, 4" ed., published by the American Psychiatric Association (DSM-IV). It is a neu rodegenerative disorder, clinically characterized by progres sive loss of memory and general cognitive function, and pathologically characterized by the deposition of extracellu lar proteinaceous plaques in the cortical and associative brain regions of Sufferers. These plaques mainly comprise fibrillar aggregates of B-amyloid peptide (AB). A? is formed from amyloid precursor protein (APP) via separate intracellular proteolytic events involving the enzymes B-secretase and Y-secretase. Variability in the site of the proteolysis mediated by Y-secretase results in AB of varying chain length, eg Af3 (1-38), AB (1-40) and AB (1-42). N-terminal truncations Such as AB (4-42) are also found in the brain, possibly as a result of variability in the site of proteolysis mediated by B-secretase. For the sake of …