Abstract
This letter describes the discovery and SAR optimization of tetrazoyl tetrahydroquinoline derivatives as potent CETP inhibitors. Compound 6m exhibited robust HDL-c increase in hCETP/hApoA1 double transgenic model and favorable pharmacokinetic properties.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Apolipoprotein A-I / genetics
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Apolipoprotein A-I / metabolism
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Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
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Cholesterol Ester Transfer Proteins / genetics
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Cholesterol Ester Transfer Proteins / metabolism
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Cholesterol, HDL / drug effects
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Cholesterol, HDL / metabolism
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Dogs
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Drug Design*
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Female
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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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Injections, Intravenous
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Male
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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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Rats
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Rats, Sprague-Dawley
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Structure-Activity Relationship
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Tetrazoles / chemical synthesis*
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Tetrazoles / chemistry
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Tetrazoles / pharmacokinetics
Substances
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Apolipoprotein A-I
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Cholesterol Ester Transfer Proteins
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Cholesterol, HDL
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Hypolipidemic Agents
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Quinolines
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Tetrazoles
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1,2,3,4-tetrahydroquinoline