Design and synthesis of potent inhibitors of cholesteryl ester transfer protein (CETP) exploiting a 1,2,3,4-tetrahydroquinoline platform.
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.
Rano
Thomas A
TA
Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Metabolic Disorders Team, 1000 Route 202, P.O. Box 300, Raritan, NJ 08869, USA.
Sieber-McMaster
Ellen
E
Pelton
Patricia D
PD
Yang
Maria
M
Demarest
Keith T
KT
Kuo
Gee-Hong
GH