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.
Copyright 2010 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
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Cholesterol Ester Transfer Proteins / metabolism
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Dogs
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Humans
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Hypolipidemic Agents / chemical synthesis
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Hypolipidemic Agents / chemistry*
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Hypolipidemic Agents / pharmacokinetics
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Mice
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Mice, Transgenic
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Quinolines / chemical synthesis
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Quinolines / chemistry*
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Quinolines / pharmacokinetics
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Quinolines / pharmacology
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Rats
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Stereoisomerism
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Structure-Activity Relationship
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Tetrahydronaphthalenes / chemistry
Substances
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Cholesterol Ester Transfer Proteins
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Hypolipidemic Agents
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Quinolines
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Tetrahydronaphthalenes
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torcetrapib