Metabolism and structure activity data based drug design: Discovery of (-)SCH 53079 an analog of the potent cholesterol absorption inhibitor (-)SCH 48461

Based on the metabolism of the potent cholesterol absorption inhibitor (-) SCH48461 and structure activity relationship information, we designed and evaluated (-)SCH 53079. This compound was found to be equipotent to (-)SCH 48461 in both the cholesterol-fed hamster and rhesus monkey assays. Importantly, (-)SCH 53079 was metabolically more stable than (-)SCH 48461 and as desired had very low plasma levels and did not cause hepatic enzyme induction. Copyright (C) 1996 Elsevier Science Ltd