Potent, cell active, non-thiol tetrapeptide inhibitors of farnesyltransferase

被引：93

作者：

Hunt, JT ^{[1
]}

Lee, VG ^{[1
]}

Leftheris, K ^{[1
]}

Seizinger, B ^{[1
]}

Carboni, J ^{[1
]}

Mabus, J ^{[1
]}

Ricca, C ^{[1
]}

Yan, N ^{[1
]}

Manne, V ^{[1
]}

机构：

[1] BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT BIOMOLEC DRUG DISCOVERY,PRINCETON,NJ 08543

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1996年 / 39卷 / 02期

关键词：

D O I：

10.1021/jm9507284

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

All previously reported CAAX-based farnesyltransferase inhibitors contain a thiol functionality. We report that attachment of the 4-imidazolyl group, via 1-, 2-, or 3-carbon alkyl or alkanoyl spacers, to Val-Tic-Met or tLeu-Tic-Gln provides potent FT inhibitors. (R*)-N-[1,2,3,4-Tetrahydro-2-[N-[2-(1H-imidazol-4-yl)ethyl-L-valyl]-3-isoquinolinyl]carbonyl]-L-methionine ([imidazol-4-yl-ethyl]-val-Tic-Met), with FT IC50 = 0.79 nM, displayed potent cell activity in the absence of prodrug formation (SAG EC(50) = 3.8 mu M).

引用

页码：353 / 358

页数：6

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