Mereaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors

被引：33

作者：

Anandan, SK ^{[1
]}

Ward, JS ^{[1
]}

Brokx, RD ^{[1
]}

Bray, MR ^{[1
]}

Patel, DV ^{[1
]}

Xiao, XX ^{[1
]}

机构：

[1] Miikana Therapeut Inc, Fremont, CA 94555 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 08期

关键词：

histone deacetylase inhibitor; non-hydroxamates; mercaptoamides;

D O I：

10.1016/j.bmcl.2005.02.075

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Inhibitors of historic deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. A mercaptoamide functionality was designed as a bidentate zinc chelator and incorporated into the hydroxamic acid based SAHA (1) scaffold in order to identify non-hydroxamate compounds as potential inhibitors of historic deacetylases. Two sets of mercaptoamides 2 and 3 with varying spacer length were synthesized and their HDAC inhibitory activity was evaluated. Low micromolar inhibition was observed for mercaptoamides 2e, 3b, and 3d. (c) 2005 Elsevier Ltd. All rights reserved.

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页码：1969 / 1972

页数：4

相关论文

共 33 条

[1] Chemistry and biology of mercaptoacetamides as novel histone deacetylase inhibitors [J].

Chen, B ;

Petukhov, PA ;

Jung, M ;

Velena, A ;

Eliseeva, E ;

Dritschilo, A ;

Kozikowski, AP .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (05) :1389-1392

[2]

Curtin ML, 2002, EXPERT OPIN THER PAT, V12, P1375

[3] Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors [J].

Finnin M.S. ;

Donigian J.R. ;

Cohen A. ;

Richon V.M. ;

Rifkind R.A. ;

Marks P.A. ;

Breslow R. ;

Pavletich N.P. .

Nature, 1999, 401 (6749) :188-193

[4] Trifluoromethyl ketones as inhibitors of histone deacetylase [J].

Frey, RR ;

Wada, CK ;

Garland, RB ;

Curtin, ML ;

Michaelides, MR ;

Li, JL ;

Pease, LJ ;

Glaser, KB ;

Marcotte, PA ;

Bouska, JJ ;

Murphy, SS ;

Davidsen, SK .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (23) :3443-3447

[5]

Furumai R, 2002, CANCER RES, V62, P4916

[6] Differential protein acetylation induced by novel histone deacetylase inhibitors [J].

Glaser, KB ;

Li, J ;

Pease, LJ ;

Staver, MJ ;

Marcotte, PA ;

Guo, J ;

Frey, RR ;

Garland, RB ;

Heyman, HR ;

Wada, CK ;

Vasudevan, A ;

Michaelides, MR ;

Davidsen, SK ;

Curtin, ML .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 325 (03) :683-690

[7] Deacetylase enzymes: biological functions and the use of small-molecule inhibitors [J].

Grozinger, CM ;

Schreiber, SL .

CHEMISTRY & BIOLOGY, 2002, 9 (01) :3-16

[8] Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation [J].

Haggarty, SJ ;

Koeller, KM ;

Wong, JC ;

Grozinger, CM ;

Schreiber, SL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (08) :4389-4394

[9] Inhibitors of histone deacetylase as new anticancer agents [J].

Jung, M .

CURRENT MEDICINAL CHEMISTRY, 2001, 8 (12) :1505-1511

[10] Phosphorus-based SAHA analogues as histone deacetylase inhibitors [J].

Kapustin, GV ;

Fejér, G ;

Gronlund, JL ;

McCafferty, DG ;

Seto, E ;

Etzkorn, FA .

ORGANIC LETTERS, 2003, 5 (17) :3053-3056

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