Aminopropylindenes derived from Grundmann%26apos;s ketone as a novel chemotype of oxidosqualene cyclase inhibitors

作者：Lange Stefanie; Keller Marco; Mueller Christoph; Oliaro Bosso Simonetta; Balliano Gianni; Bracher Franz^*

来源：European Journal of Medicinal Chemistry, 2013, 63: 758-764.

DOI：10.1016/j.ejmech.2013.03.002

• Oxidosqualene cyclase
• Enzyme inhibitor
• High energy intermediate
• Secosteroid
• Species selectivity

A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the oxidosqualene cyclase(1) (OSC)-mediated cyclization of 2,3-oxidosqualen to lanosterol was prepared from Grundmann%26apos;s ketone. Screening on OSCs from five different organisms revealed interesting activities and selectivities of some of the compounds. A N,N-dimethylaminopropyl derivative showed promising inhibition of Trypanosoma cruzi OSC in combination with low cytotoxicity, and showed significant reduction of cholesterol biosynthesis in a human cell line.

• 出版日期2013-5