piperidines and benzohydrol

To obtain small and efficient squalene synthase inhibitors, a flexible 2-aminobenzhydrol open form structure was designed and showed potent inhibitory activity comparable to 4,1-benzoxazepin compounds. Further chemical modification led to the discovery of a novel template with a strong squalene synthase inhibitory activity, and its basic structure-activity relationship was revealed. The X-ray crystallographic data of compound 12 bound to the active site of squalene synthase provided an important insight into the binding mode of this alternative template that formed 11-membered ring conformations with an intramolecular hydrogen bond.

Topics: Benzhydryl Compounds; Binding Sites; Catalytic Domain; Crystallography, X-Ray; Drug Evaluation, Preclinical; Enzyme Inhibitors; Farnesyl-Diphosphate Farnesyltransferase; Hydrogen Bonding; Molecular Conformation; Piperidines; Structure-Activity Relationship

Topics: Benzhydryl Compounds; Methylphenidate; Piperidines; Schizophrenia

Topics: Benzhydryl Compounds; Biomedical Research; Piperidines; Schizophrenia

Topics: Benzhydryl Compounds; Central Nervous System Stimulants; Obesity; Piperidines