Tetrazole and ester substituted tetrahydoquinoxalines as potent cholesteryl ester transfer protein inhibitors.
Cholesteryl ester transfer protein is a plasma glycoprotein that transfers cholesterol ester between lipoprotein particles. Inhibition of this protein, in vitro and in vivo, produces an increase in plasma high density lipoprotein cholesterol (HDL-C). This communication will describe the SAR and synthesis of a series of substituted tetrahydroquinoxaline CETP inhibitors from early mu lead to advanced enantiomerically pure analogs.
Eary
C Todd
CT
Array BioPharma, 3200 Walnut Street Boulder, CO 80301, USA. teary@arraybiopharma.com
Jones
Zachary S
ZS
Groneberg
Robert D
RD
Burgess
Laurence E
LE
Mareska
David A
DA
Drew
Mark D
MD
Blake
James F
JF
Laird
Ellen R
ER
Balachari
Devan
D
O'Sullivan
Michael
M
Allen
Andrew
A
Marsh
Vivienne
V
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000378:metabolism; D015195:Drug Design; D004952:Esters / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry*
D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004952:Esters; D011810:Quinoxalines; D013777:Tetrazoles