Aryloxy substituted N-arylpiperazinones as dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I.
A series of aryloxy substituted piperazinones with dual farnesyltransferase/geranylgeranyltransferase-I inhibitory activity was prepared. These compounds were found to have potent inhibitory activity in vitro and are promising agents for the inhibition of Ki-Ras signaling.
Bergman
J M
JM
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
Abrams
M T
MT
Davide
J P
JP
Greenberg
I B
IB
Robinson
R G
RG
Buser
C A
CA
Huber
H E
HE
Koblan
K S
KS
Kohl
N E
NE
Lobell
R B
RB
Graham
S L
SL
Hartman
G D
GD
Williams
T M
TM
Dinsmore
C J
CJ
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D011905:Genes, ras / Q000187:drug effects; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D010879:Piperazines; D011108:Polymers; C017027:arylox; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase