Evaluation of amino acid-based linkers in potent macrocyclic inhibitors of farnesyl-protein transferase

被引：7

作者：

Beshore, DC ^{[1
]}

Bell, IM

Dinsmore, CJ

Homnick, CF

Culberson, JC

Robinson, RG

Fernandes, C

Walsh, ES

Abrams, MT

Bhimnathwala, HG

Davide, JP

Ellis-Hutchings, MS

Huber, HA

Koblan, KS

Buser, CA

Kohl, NE

Lobell, RB

Chen, IW

McLoughlin, DA

Olah, TV

Graham, SL

Hartman, GD

Williams, TM

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

[3] Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA

[4] Merck Res Labs, Dept Mol Syst, W Point, PA 19486 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 14期

关键词：

D O I：

10.1016/S0960-894X(01)00340-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of amino acid-based linkers was used to investigate the effects of various substituents upon the potency, pharmacokinetic properties, and conformation of macrocyclic farnesyl-protein transferase inhibitors (FTIs). As a result of the studies described herein, highly potent FTIs with improved pharmacokinetic profiles have been identified. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：1817 / 1821

页数：5

共 17 条

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

Bell, IM .

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

[2]

BELL IM, 2001, ENZ MECH 17 C MARC I

[3] 3,8-diazabicyclo[3.2.1]octan-2-one peptide mimetics: Synthesis of a conformationally restricted inhibitor of farnesyltransferase [J].

Dinsmore, CJ ;

Bergman, JM ;

Bogusky, MJ ;

Culterson, JC ;

Hamilton, KA ;

Graham, SL .

ORGANIC LETTERS, 2001, 3 (06) :865-868

[4] Conformational restriction of flexible ligands guided by the transferred NOE experiment: Potent macrocyclic inhibitors of farnesyltransferase [J].

Dinsmore, CJ ;

Bogusky, MJ ;

Culberson, JC ;

Bergman, JM ;

Homnick, CF ;

Zartman, CB ;

Mosser, SD ;

Schaber, MD ;

Robinson, RG ;

Koblan, KS ;

Huber, HE ;

Graham, SL ;

Hartman, GD ;

Huff, JR ;

Williams, TM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (09) :2107-2108

[5]

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

[6] RAS C-TERMINAL PROCESSING ENZYMES - MINIREVIEW NEW DRUG TARGETS [J].

GIBBS, JB .

CELL, 1991, 65 (01) :1-4

[7] 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

[8]

HUBER HE, 2000, P AM ASSOC CANC RES, V41, P2838

[9] ISOPRENOID ADDITION TO RAS PROTEIN IS THE CRITICAL MODIFICATION FOR ITS MEMBRANE ASSOCIATION AND TRANSFORMING ACTIVITY [J].

KATO, K ;

COX, AD ;

HISAKA, MM ;

GRAHAM, SM ;

BUSS, JE ;

DER, CJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (14) :6403-6407

[10]

Kearsley S.K, UNPUB

← 1 2 →