Design, synthesis, and structure-activity relationships of tetrahydroquinoline-based farnesyltransferase inhibitors.
Tetrahydroquinoline-based small molecule inhibitors of farnesyltransferase (FT) have been identified. Lead compounds were shown to have nanomolar to sub-nanomolar activity in biochemical assays with excellent potency in a Ras-mutated cellular reversion assay. BMS-316810 (9e), a 0.7 nM FT inhibitor, was orally-active in a nude mouse tumor allograft efficacy study.
Lombardo
Louis J
LJ
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, United States. louis.lombardo@bms.com
Camuso
Amy
A
Clark
John
J
Fager
Krista
K
Gullo-Brown
Johnni
J
Hunt
John T
JT
Inigo
Ivan
I
Kan
David
D
Koplowitz
Barry
B
Lee
Francis
F
McGlinchey
Kelly
K
Qian
Ligang
L
Ricca
Carolyn
C
Rovnyak
George
G
Traeger
Sarah
S
Tokarski
John
J
Williams
David K
DK
Wu
Laurence I
LI
Zhao
Yufen
Y
Manne
Veeraswamy
V
Bhide
Rajeev S
RS
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D051379:Mice; D008819:Mice, Nude; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011804:Quinolines; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase