Boom in the development of non-peptidic beta-secretase (BACE1) inhibitors for the treatment of Alzheimer's disease.

Beta-amyloid cleaving enzyme-1 (BACE1) has become a significant target for the therapy of Alzheimer's disease. After the discovery of the first non-peptidomimetic beta-secretase inhibitors by Takeda Chemicals in 2001, several research teams focused on SAR development of these agents. The non-peptidic BACE1 inhibitors may potentially overcome the classical problems associated with the peptide structure of first generation, such as blood-brain barrier crossing, poor oral bioavailability and susceptibility to P-glycoprotein transport. In the past 6 years a boom in research of non-peptidic BACE1 inhibitors has disseminated findings over hundreds of publications and patents. The rapidly growing literature has been reviewed with particular emphasis on literature of pharmaceutical companies. (c) 2008 Wiley Periodicals, Inc.