Discovery of hydroxyl 1, 2-diphenylethanamine analogs as potent cholesterol ester transfer protein inhibitors. Issue 14 (15th July 2016)

• Record Type: Journal Article
• Authors: Jiang, Ji; Finlay, Heather; Johnson, James A.; Harikrishnan, Lalgudi; Kamau, Muthoni; Qiao, Jennifer; Wang, Tammy; Adam, Leonard; Taylor, David; Yang, Richard; Sleph, Paul; Chen, Alice Ye A.; Yin, Xiaohong; Wexler, Ruth; Salvati, Mark E.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 14(2016)
• Page Start: 3278
• Page End: 3281
• Publication Date: 2016-07-15
• Subjects: CETP inhibitors -- HDL cholesterol -- Hydroxyl 1, 2-diphenylethanamine; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.05.058
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Hydroxyl 1, 2-diphenylethanamine analogs were identified as potent inhibitors of cholesterol ester transfer protein (CETP), a therapeutic target to raise HDL cholesterol. In an effort to improve the pharmaceutical properties in the previously disclosed DiPhenylPyridineEthanamine (DPPE) series, polar groups were introduced to the N-linked quaternary center. Optimization of analogues for potency, in vitro liability profile and efficacy led to identification of lead compound16 which demonstrated robust pharmacodynamic effects in human CETP/apo-B100 dual transgenic mice.