Synthesis and structure-activity relationships of novel benzofuran farnesyltransferase inhibitors

Kohsuke Asoh; Masami Kohchi; Ikumi Hyoudoh; Tatsuo Ohtsuka; Miyako Masubuchi; Kenichi Kawasaki; Hirosato Ebiike; Yasuhiko Shiratori; Takaaki A Fukami; Osamu Kondoh; Toshiyuki Tsukaguchi; Nobuya Ishii; Yuko Aoki; Nobuo Shimma; Masahiro Sakaitani

doi:10.1016/j.bmcl.2009.01.074

Synthesis and structure-activity relationships of novel benzofuran farnesyltransferase inhibitors

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1753-7. doi: 10.1016/j.bmcl.2009.01.074. Epub 2009 Feb 11.

Authors

Kohsuke Asoh¹, Masami Kohchi, Ikumi Hyoudoh, Tatsuo Ohtsuka, Miyako Masubuchi, Kenichi Kawasaki, Hirosato Ebiike, Yasuhiko Shiratori, Takaaki A Fukami, Osamu Kondoh, Toshiyuki Tsukaguchi, Nobuya Ishii, Yuko Aoki, Nobuo Shimma, Masahiro Sakaitani

Affiliation

¹ Kamakura Research Laboratories, Chugai Pharmaceutical Co. Ltd., 200-Kajiwara, Kamakura, Kanagawa 247-8530, Japan.

PMID: 19217288
DOI: 10.1016/j.bmcl.2009.01.074

Abstract

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.

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Benzofurans / chemical synthesis*
Benzofurans / pharmacology
Chemistry, Pharmaceutical / methods*
Crystallography, X-Ray
Drug Design
Drug Screening Assays, Antitumor
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Farnesyltranstransferase / antagonists & inhibitors*
Farnesyltranstransferase / chemistry
Humans
Inhibitory Concentration 50
Mice
Neoplasm Transplantation
Quinolones / chemical synthesis*
Quinolones / pharmacology
Structure-Activity Relationship

Substances

Antineoplastic Agents
Benzofurans
Enzyme Inhibitors
Quinolones
Farnesyltranstransferase
benzofuran
tipifarnib