Design and synthesis of novel, conformationally restricted HMG-CoA reductase inhibitors.

Abstract

Using structure-based design, a novel series of conformationally restricted, pyrrole-based inhibitors of HMG-CoA reductase were discovered. Leading analogs demonstrated potent inhibition of cholesterol synthesis in both in vitro and in vivo models and may be useful for the treatment of hypercholesterolemia and related lipid disorders.

• Authors: Jeffrey A Pfefferkorn, Chulho Choi, Yuntao Song, Bharat K Trivedi, Scott D Larsen, Valerie Askew, Lisa Dillon, Jeffrey C Hanselman, Zhiwu Lin, Gina Lu, Andrew Robertson, Catherine Sekerke, Bruce Auerbach, Alexander Pavlovsky, Melissa S Harris, Graeme Bainbridge, Nicole Caspers
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 17 Issue 16 Pg. 4531-7 (Aug 15 2007) ISSN: 0960-894X [Print] England
• PMID: 17574411 (Publication Type: Journal Article)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Pyrroles
• Cholesterol

Topics

• Animals
• Cholesterol (biosynthesis)
• Drug Design
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (chemical synthesis, pharmacology)
• Hyperlipidemias (drug therapy)
• Mice
• Molecular Biology
• Molecular Structure
• Pyrroles (chemistry, pharmacology)
• Structure-Activity Relationship