Aryloxy substituted N-arylpiperazinones as dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I

被引：29

作者：

Bergman, JM ^{[1
]}

Abrams, MT

Davide, JP

Greenberg, IB

Robinson, RG

Buser, CA

Huber, HE

Koblan, KS

Kohl, NE

Lobell, RB

Graham, SL

Hartman, GD

Williams, TM

Dinsmore, CJ

机构：

[1] Merck Res Labs, Dept Med Chem, W Point, PA 19486 USA

[2] Merck Res Labs, Dept Canc Res, W Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(01)00240-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of aryloxy substituted piperazinones with dual farnesyltransferase/geranylgeranyltransferase-I inhibitory activity was prepared. These compounds were found to have potent inhibitory activity in vitro and are promising agents for the inhibition of Ki-Ras signaling. (C) 2001 Published by Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：1411 / 1415

页数：5

相关论文

共 20 条

[1] Design and in vivo analysis of potent non-thiol inhibitors of farnesyl protein transferase [J].

Anthony, NJ ;

Gomez, RP ;

Schaber, MD ;

Mosser, SD ;

Hamilton, KA ;

O'Neil, TJ ;

Koblan, KS ;

Graham, SL ;

Hartman, GD ;

Shah, D ;

Rands, E ;

Kohl, NE ;

Gibbs, JB ;

Oliff, AI .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (17) :3356-3368

[2] Inhibitors of protein prenylation 2000 [J].

Bell, IM .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2000, 10 (12) :1813-1831

[3] TOTAL SYNTHESIS OF DEOXYBOUVARDIN AND RA-VII - MACROCYCLIZATION VIA AN INTRAMOLECULAR ULLMANN REACTION [J].

BOGER, DL ;

YOHANNES, D .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (04) :1427-1429

[4] Potent, non-thiol inhibitors of farnesyltransferase [J].

Breslin, MJ ;

deSolms, SJ ;

Giuliani, EA ;

Stokker, GE ;

Graham, SL ;

Pompliano, DL ;

Mosser, SD ;

Hamilton, KA ;

Hutchinson, JH .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (23) :3311-3316

[5]

DINSMORE CJ, 2000, CURR OPIN ONCOL ENDO, V2, P26

[6] Farnesyl protein transferase inhibitors and other therapies targeting the ras signal transduction pathway [J].

End, DW .

INVESTIGATIONAL NEW DRUGS, 1999, 17 (03) :241-258

[7] Anticancer drug targets: growth factors and growth factor signaling [J].

Gibbs, JB .

JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (01) :9-13

[8] PSEUDOPEPTIDE INHIBITORS OF RAS FARNESYL-PROTEIN TRANSFERASE [J].

GRAHAM, SL ;

DESOLMS, SJ ;

GIULIANI, EA ;

KOHL, NE ;

MOSSER, SD ;

OLIFF, AI ;

POMPLIANO, DL ;

RANDS, E ;

BRESLIN, MJ ;

DEANA, AA ;

GARSKY, VM ;

SCHOLZ, TH ;

GIBBS, JB ;

SMITH, RL .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (06) :725-732

[9]

HUBE RHE, 2000, P AM ASS CANC RES, V41

[10]

HUBER HE, IN PRESS J BIOL CHEM