Non-thiol 3-aminomethylbenzamide inhibitors of farnesyl-protein transferase.
The design and syntheses of non-thiol inhibitors of farnesyl-protein transferase are described. Substitutions on an imidazolylmethyl-AMBA-methionine template gave a highly potent and cell-active inhibitor.
Ciccarone
T M
TM
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
MacTough
S C
SC
Williams
T M
TM
Dinsmore
C J
CJ
O'Neill
T J
TJ
Shah
D
D
Culberson
J C
JC
Koblan
K S
KS
Kohl
N E
NE
Gibbs
J B
JB
Oliff
A I
AI
Graham
S L
SL
Hartman
G D
GD
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D051381:Rats; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology
D001549:Benzamides; D004791:Enzyme Inhibitors; D007093:Imidazoles; D013438:Sulfhydryl Compounds; C029899:imidazole; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase