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Bioorg Med Chem Lett ; 21(1): 488-91, 2011 Jan 01.
Article in English | MEDLINE | ID: mdl-21084191

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.


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