2-Arylbenzoxazoles as CETP inhibitors: substitution and modification of the alpha-alkoxyamide moiety.
The development of a series of 2-arylbenzoxazole alpha-alkoxyamide and beta-alkoxyamine inhibitors of cholesteryl ester transfer protein (CETP) is described. Highly fluorinated alpha-alkoxyamides proved to be potent inhibitors of CETP in vitro, and the highly fluorinated 2-arylbenzoxazole beta-alkoxyamine 4 showed a desirable combination of in vitro potency (IC(50)=151 nM) and oral bioavailability in the mouse.
Hunt
Julianne A
JA
Merck Research Laboratories, Rahway, NJ 07065, United States.
Gonzalez
Silvia
S
Kallashi
Florida
F
Hammond
Milton L
ML
Pivnichny
James V
JV
Tong
Xinchun
X
Xu
Suoyu S
SS
Anderson
Matt S
MS
Chen
Ying
Y
Eveland
Suzanne S
SS
Guo
Qiu
Q
Hyland
Sheryl A
SA
Milot
Denise P
DP
Sparrow
Carl P
CP
Wright
Samuel D
SD
Sinclair
Peter J
PJ
D000438:Alcohols / Q000138:chemical synthesis / Q000378:metabolism; D000577:Amides / Q000138:chemical synthesis / Q000378:metabolism; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000378:metabolism*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D000438:Alcohols; D000577:Amides; D001583:Benzoxazoles; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; C059688:alkoxyl radical