SCH-48461

SCH-48461 is a cholesterol absorption inhibitor.
During the early phases of an NPC1L1 inhibitor discovery program at Schering-Plough, conformationally restricted analogs based on the 2-azetidinone backbone were targeted by Burnett and co-workers. Early in the biological evaluation, it became apparent that even though the in vitro ACAT inhibitory activity of these analogs was modest, they exhibited significant activity in a cholesterol-fed hamster model. The discovery of the prototypical 2-azetidinone CAI, SCH-48461 and the details of the first-generation SAR have been described in detail.