Synthesis and structure-activity relationships of novel benzofuran farnesyltransferase inhibitors.
A series of benzofuran-based farnesyltransferase inhibitors have been designed and synthesized as antitumor agents. Among them, 11f showed the most potent enzyme inhibitory activity (IC(50)=1.1nM) and antitumor activity in human cancer xenografts in mice.
Asoh
Kohsuke
K
Kamakura Research Laboratories, Chugai Pharmaceutical Co. Ltd., 200-Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
Kohchi
Masami
M
Hyoudoh
Ikumi
I
Ohtsuka
Tatsuo
T
Masubuchi
Miyako
M
Kawasaki
Kenichi
K
Ebiike
Hirosato
H
Shiratori
Yasuhiko
Y
Fukami
Takaaki A
TA
Kondoh
Osamu
O
Tsukaguchi
Toshiyuki
T
Ishii
Nobuya
N
Aoki
Yuko
Y
Shimma
Nobuo
N
Sakaitani
Masahiro
M
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D009368:Neoplasm Transplantation; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001572:Benzofurans; D004791:Enzyme Inhibitors; D015363:Quinolones; D051231:Farnesyltranstransferase; C105430:benzofuran; C402769:tipifarnib