Diaryl ether inhibitors of farnesyl-protein transferase.
Imidazolemethyl diaryl ethers are potent inhibitors of farnesyl-protein transferase. The SNAr displacement reaction used to prepare these diaryl ethers was amenable to rapid parallel synthesis of FPTase inhibitors. The use of a broad range of commercially available phenols quickly identified compounds which proved active in cells.
Mactough
S C
SC
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486. USA. sue_mactough@merck.com
Desolms
S J
SJ
Shaw
A W
AW
Abrams
M T
MT
Ciccarone
T M
TM
Davide
J P
JP
Hamilton
K A
KA
Hutchinson
J H
JH
Koblan
K S
KS
Kohl
N E
NE
Lobell
R B
RB
Robinson
R G
RG
Graham
S L
SL
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D007093:Imidazoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D019151:Peptide Library; D010647:Phenyl Ethers / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007093:Imidazoles; D019151:Peptide Library; D010647:Phenyl Ethers; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; C064911:p21(ras) farnesyl-protein transferase