Optimization of a series of potent and selective ketone histone deacetylase inhibitors

被引：12

作者：

Pescatore, Giovanna ^{[1
]}

Kinzel, Olaf ^{[1
]}

Attenni, Barbara ^{[1
]}

Cecchetti, Ottavia ^{[1
]}

Fiore, Fabrizio ^{[1
]}

Fonsi, Massimiliano ^{[1
]}

Rowley, Michael ^{[1
]}

Schultz-Fademrecht, Carsten ^{[1
]}

Serafini, Sergio ^{[1
]}

Steinkuehler, Christian ^{[1
]}

Jones, Philip ^{[1
]}

机构：

[1] IRBM Merck Res Labs, I-00040 Pomezia, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 20期

关键词：

HDAC inhibitors; alkyl ketone; zinc binding group;

D O I：

10.1016/j.bmcl.2008.09.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Histone deacetylase (HDAC) inhibitors offer a promising strategy for cancer therapy and the first generation HDAC inhibitors are currently in the clinic. Herein we describe the optimization of a series of ketone small molecule HDAC inhibitors leading to potent and selective class I HDAC inhibitors with good dog PK. (c) 2008 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5528 / 5532

页数：5

相关论文

共 23 条

[1] Recent Advances in the Medicinal Chemistry of Histone Deacetylase Inhibitors [J].

Brittain, Dominic ;

Weinmann, Hilmar ;

Ottow, Eckhard .

ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 42, 2007, 42 :337-348

[2] Short-Chain Fatty Acid Inhibitors of Histone Deacetylases: Promising Anticancer Therapeutics? [J].

Chen, James S. ;

Faller, Douglas V. ;

Spanjaard, Remco A. .

CURRENT CANCER DRUG TARGETS, 2003, 3 (03) :219-236

[3] MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo [J].

Fournel, Marielle ;

Bonfils, Claire ;

Hou, Yu ;

Yan, Pu Theresa ;

Trachy-Bourget, Marie-Claude ;

Kalita, Ann ;

Liu, Jianhong ;

Lu, Ai-Hua ;

Zhou, Nancy Z. ;

Robert, Marie-France ;

Gillespie, Jeffrey ;

Wang, James J. ;

Ste-Croix, Helene ;

Rahil, Jubrail ;

Lefebvre, Sylvain ;

Moradei, Oscar ;

Delorme, Daniel ;

MacLeod, A. Robert ;

Besterman, Jeffrey M. ;

Li, Zuomei .

MOLECULAR CANCER THERAPEUTICS, 2008, 7 (04) :759-768

[4]

Furumai R, 2002, CANCER RES, V62, P4916

[5] Histone deacetylases and cancer [J].

Glozak, M. A. ;

Seto, E. .

ONCOGENE, 2007, 26 (37) :5420-5432

[6] Vorinostat [J].

Grant, Steven ;

Easley, Chris ;

Kirkpatrick, Peter .

NATURE REVIEWS DRUG DISCOVERY, 2007, 6 (01) :21-22

[7]

Han JW, 2000, CANCER RES, V60, P6068

[8] Histone-deacetylase inhibitors: Novel drugs for the treatment of cancer [J].

Johnstone, RW .

NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (04) :287-299

[9] A novel series of potent and selective ketone histone deacetylase inhibitors with antitumor activity in vivo [J].

Jones, Philip ;

Altamura, Sergio ;

De Francesco, Raffaele ;

Paz, Odalys Gonzalez ;

Kinzel, Olaf ;

Mesiti, Giuseppe ;

Monteagudo, Edith ;

Pescatore, Giovanna ;

Rowley, Michael ;

Verdirame, Maria ;

Steinkijhler, Christian .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (08) :2350-2353

[10] From natural products to small molecule ketone histone deacetylase inhibitors:: Development of new class specific agents [J].

Jones, Philip ;

Steinkuhler, Christian .

CURRENT PHARMACEUTICAL DESIGN, 2008, 14 (06) :545-561