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 (e.g., IC<sub>50</sub> values of 2âÂÂ50 mM), they exhibited significant activity in a cholesterol-fed hamster model (CFH). The discovery of the prototypical 2-azetidinone CAI, SCH-48461 (ACAT IC<sub>50</sub> ~26 mM, ED<sub>50</sub> of CE reduction in hamsters ~2.2 mpk) and the details of the first-generation SAR have been described in detail.