Chromanol derivatives--a novel class of CETP inhibitors

Alexandros Vakalopoulos; Carsten Schmeck; Michael Thutewohl; Volkhart Li; Hilmar Bischoff; Klemens Lustig; Olaf Weber; Holger Paulsen; Harry Elias

doi:10.1016/j.bmcl.2010.10.110

Chromanol derivatives--a novel class of CETP inhibitors

Bioorg Med Chem Lett. 2011 Jan 1;21(1):488-91. doi: 10.1016/j.bmcl.2010.10.110. Epub 2010 Oct 26.

Authors

Alexandros Vakalopoulos¹, Carsten Schmeck, Michael Thutewohl, Volkhart Li, Hilmar Bischoff, Klemens Lustig, Olaf Weber, Holger Paulsen, Harry Elias

Affiliation

¹ Bayer HealthCare AG, Bayer Schering Pharma, Global Drug Discovery, D-42096 Wuppertal, Germany. [email protected]

PMID: 21084191
DOI: 10.1016/j.bmcl.2010.10.110

Abstract

Based on our former development candidate BAY 38-1315, optimization efforts led to the discovery of a novel chemical class of orally active cholesteryl ester transfer protein (CETP) inhibitors. The chromanol derivative 19b is a highly potent CETP inhibitor with favorable pharmacokinetic properties suitable for clinical studies. Chemical process optimization furnished a robust synthesis for a kilogram-scale process.

MeSH terms

Administration, Oral
Animals
Benzopyrans / chemical synthesis
Benzopyrans / chemistry*
Benzopyrans / pharmacokinetics
Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
Cholesterol Ester Transfer Proteins / metabolism
Cholesterol, HDL / metabolism
Chromans / chemical synthesis
Chromans / chemistry*
Chromans / pharmacokinetics
Dogs
Humans
Mice
Mice, Transgenic
Rats
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry*
Spiro Compounds / pharmacokinetics
Structure-Activity Relationship

Substances

Benzopyrans
Cholesterol Ester Transfer Proteins
Cholesterol, HDL
Chromans
Spiro Compounds
2,2,5,7,8-pentamethyl-1-hydroxychroman