Abstract
This manuscript describes the design and synthesis of a series of pyrrole-based inhibitors of HMG-CoA reductase for the treatment of hypercholesterolemia. Analogs were optimized using structure-based design and physical property considerations resulting in the identification of 44, a hepatoselective HMG-CoA reductase inhibitor with excellent acute and chronic efficacy in a pre-clinical animal models.
MeSH terms
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Animals
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Cricetinae
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Dose-Response Relationship, Drug
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Drug Design
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Fluorobenzenes
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / chemistry*
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
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Hyperlipidemias / drug therapy
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Liver / drug effects
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Models, Molecular
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Molecular Structure
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Pyrimidines
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Pyrroles / chemistry*
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Pyrroles / pharmacology*
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Rosuvastatin Calcium
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Structure-Activity Relationship
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Sulfonamides
Substances
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Fluorobenzenes
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Pyrimidines
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Pyrroles
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Sulfonamides
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Rosuvastatin Calcium