Background and Objectives: A number of BACE1 inhibitors have been tested in clinical trials but have been discontinued due to lack of efficacy or unacceptable side effects. In this study, we investigate the physicochemical properties of some of these ligands and their binding affinity for the molecular model of the BACE1 enzyme [PDB ID: 6EQM]. Materials and Methods: The molecular model of the human BACE-1 enzyme [PDB ID: 6EQM] and the ligands studied were obtained from www.rcsb.org and the PubChem database. The physicochemical properties, the possibility of gastrointestinal absorption and blood-brain barrier crossing of the studied compounds were taken from the Swiss Adam database. After preparing the enzyme model and its ligands by molegro visual docker software (v5), we performed the molecular docking process for all studied ligands. Results: According to the results of Swiss Adam software, of the compounds studied, only AZD-3293 can cross the blood-brain barrier. This compound also has a high affinity for the active site of the enzyme. PF -06751979 had the highest affinity based on the docking score for the active site of the enzyme, but it also has low gastrointestinal absorption and cannot cross the blood-brain barrier. Discussion: Many clinical trials in which beta-secretase-1 inhibitors were administered resulted in successful inhibition of beta-secretase activity and a reduction in beta-amyloid production and beta-amyloid concentration in serum and cerebrospinal fluid. However, most of these trials were discontinued in the long term due to the ineffectiveness of this treatment method and did not improve disease symptoms in Alzheimer's patients. Conclusion: A BACE1 inhibitor that cannot cross the blood-brain barrier cannot affect neurons. For agents that can cross the blood-brain barrier, such as AZD-3293, the results of previous studies have shown no improvement in memory loss and other cognitive disorders associated with Alzheimer's disease, and the agent has very severe side effects.