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

b-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 b-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.