Oxo-piperazine derivatives of N-arylpiperazinones as inhibitors of farnesyltransferase.
The evaluation of SAR associated with the insertion of carbonyl groups at various positions of N-arylpiperazinone farnesyltransferase inhibitors is described herein. 1-Aryl-2,3-diketopiperazine derivatives exhibited the best balance of potency and pharmacokinetic profile relative to the parent 1-aryl-2-piperazinones.
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. christopher_dinsmore@merck.com
C J
CJ
Dinsmore
J M
JM
Bergman
D D
DD
Wei
C B
CB
Zartman
J P
JP
Davide
I B
IB
Greenberg
D
D
Liu
T J
TJ
O'Neill
J B
JB
Gibbs
K S
KS
Koblan
N E
NE
Kohl
R B
RB
Lobell
I W
IW
Chen
D A
DA
McLoughlin
T V
TV
Olah
S L
SL
Graham
G D
GD
Hartman
T M
TM
Williams
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D004285:Dogs; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D010879:Piperazines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D010879:Piperazines; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase