Synthesis of C-11 methyl-substituted benzocycloheptapyridine inhibitors of farnesyl protein transferase.
[formula: see text] Synthesis of C-11 methyl-substituted benzocycloheptylpyridine tricyclic compounds has been achieved via two different methods. Methylation of C-11 has been effected by treatment of amine 4 with BuLi followed by Mel quenching. In a similar procedure, introduction of a C-11 substituent with concomitant rearrangement of the exocyclic double bond has been carried out. Potent farnesyl protein transferase inhibitors have been synthesized using the above methodologies.
Njoroge
F G
FG
Schering-Plough Research Institute, Department of Chemistry, Kenilworth, New Jersey 07033, USA.
Vibulbhan
B
B
Wong
J K
JK
White
S K
SK
Wong
S C
SC
Carruthers
N I
NI
Kaminski
J J
JJ
Doll
R J
RJ
Girijavallabhan
V
V
Ganguly
A K
AK
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011725:Pyridines; C409082:benzocycloheptapyridine; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase