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

Thomas A Rano; Ellen Sieber-McMaster; Patricia D Pelton; Maria Yang; Keith T Demarest; Gee-Hong Kuo

doi:10.1016/j.bmcl.2009.03.051

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

Bioorg Med Chem Lett. 2009 May 1;19(9):2456-60. doi: 10.1016/j.bmcl.2009.03.051. Epub 2009 Mar 18.

Authors

Thomas A Rano¹, Ellen Sieber-McMaster, Patricia D Pelton, Maria Yang, Keith T Demarest, Gee-Hong Kuo

Affiliation

¹ Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Metabolic Disorders Team, 1000 Route 202, P.O. Box 300, Raritan, NJ 08869, USA.

PMID: 19339179
DOI: 10.1016/j.bmcl.2009.03.051

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.

MeSH terms

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

Substances

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