Novel tetrahydrochinoline derived CETP inhibitors

Carsten Schmeck; Heike Gielen-Haertwig; Alexandros Vakalopoulos; Hilmar Bischoff; Volkhart Li; Gabriele Wirtz; Olaf Weber

doi:10.1016/j.bmcl.2010.01.071

Novel tetrahydrochinoline derived CETP inhibitors

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1740-3. doi: 10.1016/j.bmcl.2010.01.071. Epub 2010 Jan 21.

Authors

Carsten Schmeck¹, Heike Gielen-Haertwig, Alexandros Vakalopoulos, Hilmar Bischoff, Volkhart Li, Gabriele Wirtz, Olaf Weber

Affiliation

¹ Bayer HealthCare AG, Bayer Schering Pharma, Global Drug Discovery, D-42096 Wuppertal, Germany. carsten.schmeck@bayerhealthcare.com

PMID: 20137927
DOI: 10.1016/j.bmcl.2010.01.071

Abstract

In the course of our efforts to identify orally active cholesteryl ester transfer protein (CETP) inhibitors, we have continued to explore tetrahydrochinoline derivatives. Based on BAY 19-4789 structural modifications led to the discovery of novel cycloalkyl substituted compounds. Thus, example 11b is a highly potent CETP inhibitor both in vitro and in vivo in transgenic mice with favourable pharmacokinetic properties for clinical development.

MeSH terms

Animals
Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
Cholesterol Ester Transfer Proteins / metabolism
Dogs
Humans
Hypolipidemic Agents / chemical synthesis
Hypolipidemic Agents / chemistry*
Hypolipidemic Agents / pharmacokinetics
Mice
Mice, Transgenic
Quinolines / chemical synthesis
Quinolines / chemistry*
Quinolines / pharmacokinetics
Quinolines / pharmacology
Rats
Stereoisomerism
Structure-Activity Relationship
Tetrahydronaphthalenes / chemistry

Substances

Cholesterol Ester Transfer Proteins
Hypolipidemic Agents
Quinolines
Tetrahydronaphthalenes
torcetrapib