Design and synthesis of potent inhibitors of cholesteryl ester transfer protein (CETP) exploiting a 1,2,3,4-tetrahydroquinoline platform.

Abstract

Tetrahydroquinoline A is a potent inhibitor of the cholesterol ester transfer protein (CETP), a target for the treatment of low HDL-C and atherosclerosis. Low HDL-C has been identified as a key risk factor for cardiovascular disease in addition to high LDL-C, the target of the statin drugs. Tetrahydroquinoline A inhibits partially purified CETP with an IC(50) of 39nM. The preparation of a series of potent inhibitors of CETP designed around a 1,2,3,4-tetrahydroquinoline platform will be discussed.

• Authors: Thomas A Rano, Ellen Sieber-McMaster, Patricia D Pelton, Maria Yang, Keith T Demarest, Gee-Hong Kuo
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 19 Issue 9 Pg. 2456-60 (May 01 2009) ISSN: 1464-3405 [Electronic] England
• PMID: 19339179 (Publication Type: Journal Article)

Chemical References

• CETP protein, human
• Cholesterol Ester Transfer Proteins
• Cholesterol, HDL
• Quinolines
• 1,2,3,4-tetrahydroquinoline

Topics

• Animals
• Atherosclerosis (drug therapy, metabolism)
• Cardiovascular Diseases (prevention & control)
• Chemistry, Pharmaceutical (methods)
• Cholesterol Ester Transfer Proteins (antagonists & inhibitors, chemistry)
• Cholesterol, HDL (metabolism)
• Dogs
• Drug Design
• Haplorhini
• Humans
• Inhibitory Concentration 50
• Mice
• Models, Chemical
• Quinolines (chemical synthesis, pharmacology)
• Risk Factors