Patents targeting γ-secretase inhibition and modulation for the treatment of Alzheimer's disease:: 2004-2008

Background: Although Alzheimer's disease has been defined for over a century, at present there is no effective treatment. Amyloid deposition and plaque formation are widely believed to contribute to the pathology of the disease. As the etiology of plaque formation has become better understood, the search for therapies has bred small molecules capable of inhibiting or regulating the activity of gamma-secretase. Objective: This paper reviews patents from the past 4 years claiming modulators or inhibitors of gamma-secretase as a treatment for Alzheimer's disease. Method: One or two compounds from each patent were selected to represent the claimed chemical space. Compound selection was influenced by literature accounts, which are also discussed. Although an attempt has been made to include major contributions in the field, the list of patents reviewed should not be considered exhaustive. Conclusion: This review seeks to expand upon a previous review covering patents from 2000 - 2004. Since then there has been an increase in the number of structural and mechanistic approaches being pursued and several compounds have entered the clinic.