1260001-12-4Relevant articles and documents
Spiroimidazolidinone NPC1L1 inhibitors. Part 2: Structure-activity studies and in vivo efficacy
Howell, Kobporn L.,Devita, Robert J.,Garcia-Calvo, Margarita,Meurer, Roger D.,Lisnock, Jeanmarie,Bull, Herbert G.,McMasters, Daniel R.,McCann, Margaret E.,Mills, Sander G.
scheme or table, p. 6929 - 6932 (2011/02/16)
Ezetimibe (Zetia), a cholesterol-absorption inhibitor (CAI) approved by the FDA for the treatment of hypercholesterolemia, is believed to target the intestine protein Niemann-Pick C1-Like 1 (NPC1L1) or its pathway. A spiroimidazolidinone NPC1L1 inhibitor identified by virtual screening showed moderate binding activity but was not efficacious in an in vivo rodent model of cholesterol absorption. Synthesis of analogs established the structure-activity relationships for binding activity, and resulted in compounds with in vivo efficacy, including 24, which inhibited plasma cholesterol absorption by 67% in the mouse, thereby providing proof-of-concept that non-β-lactams can be effective CAIs.
