Tetrazole and ester substituted tetrahydoquinoxalines as potent cholesteryl ester transfer protein inhibitors

C Todd Eary; Zachary S Jones; Robert D Groneberg; Laurence E Burgess; David A Mareska; Mark D Drew; James F Blake; Ellen R Laird; Devan Balachari; Michael O'Sullivan; Andrew Allen; Vivienne Marsh

doi:10.1016/j.bmcl.2007.01.112

Tetrazole and ester substituted tetrahydoquinoxalines as potent cholesteryl ester transfer protein inhibitors

Bioorg Med Chem Lett. 2007 May 1;17(9):2608-13. doi: 10.1016/j.bmcl.2007.01.112. Epub 2007 Feb 8.

Authors

C Todd Eary¹, Zachary S Jones, Robert D Groneberg, Laurence E Burgess, David A Mareska, Mark D Drew, James F Blake, Ellen R Laird, Devan Balachari, Michael O'Sullivan, Andrew Allen, Vivienne Marsh

Affiliation

¹ Array BioPharma, 3200 Walnut Street Boulder, CO 80301, USA. [email protected]

PMID: 17331716
DOI: 10.1016/j.bmcl.2007.01.112

Abstract

Cholesteryl ester transfer protein is a plasma glycoprotein that transfers cholesterol ester between lipoprotein particles. Inhibition of this protein, in vitro and in vivo, produces an increase in plasma high density lipoprotein cholesterol (HDL-C). This communication will describe the SAR and synthesis of a series of substituted tetrahydroquinoxaline CETP inhibitors from early mu lead to advanced enantiomerically pure analogs.

MeSH terms

Animals
Chemistry, Pharmaceutical / methods*
Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
Cholesterol, HDL / metabolism
Drug Design
Esters / chemistry*
Humans
Hydrogen-Ion Concentration
Inhibitory Concentration 50
Molecular Conformation
Quinoxalines / chemical synthesis*
Quinoxalines / pharmacology*
Rats
Stereoisomerism
Structure-Activity Relationship
Tetrazoles / chemistry*

Substances

Cholesterol Ester Transfer Proteins
Cholesterol, HDL
Esters
Quinoxalines
Tetrazoles