Abstract
We have recently reported the discovery of the new benzhydrol template, which has a highly potent inhibitory activity for squalene synthase, as typified by compound 1 (SSI IC(50)=0.85 nM). However, it was composed of a pair of easy rotatable atropisomers. In the effort to fix the isomerization, a highly potent alkoxy-aminobenzhydrol scaffold was developed. Some of these acquired compounds demonstrating strong cholesterol synthesis inhibitory activities in a rat hepatic cell. Moreover, two of the series compounds exhibited specific plasma lipid-lowering effects in in vivo animal models.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Animals
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Anticholesteremic Agents / chemical synthesis
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Anticholesteremic Agents / chemistry*
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Anticholesteremic Agents / pharmacokinetics
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Benzhydryl Compounds / chemical synthesis
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Benzhydryl Compounds / chemistry*
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Benzhydryl Compounds / pharmacokinetics
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Binding Sites
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Callithrix
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Computer Simulation
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Cricetinae
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Drug Evaluation, Preclinical
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacokinetics
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Farnesyl-Diphosphate Farnesyltransferase / antagonists & inhibitors*
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Farnesyl-Diphosphate Farnesyltransferase / metabolism
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Female
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Hepatocytes / drug effects
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Isomerism
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Male
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Models, Animal
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Rats
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Structure-Activity Relationship
Substances
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Anticholesteremic Agents
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Benzhydryl Compounds
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Enzyme Inhibitors
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Farnesyl-Diphosphate Farnesyltransferase
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benzohydrol