Benzo[b]thiophene-based histione deacetylase inhibitors

被引：36

作者：

Witter, David J.

Belvedere, Sandro

Chen, Liqiang

Secrist, J. Paul

Mosley, Ralph T.

Miller, Thomas A.

机构：

[1] Merck Res Labs, Dept Drug Design & Optimizat, Boston, MA 02115 USA

[2] Merck Res Labs, Dept Canc & Biol Therapeut, Boston, MA 02115 USA

[3] ARMGo Pharm Inc, New York, NY 10032 USA

[4] Univ Minnesota, Ctr Drug Design, Minneapolis, MN 55455 USA

[5] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 16期

关键词：

HDAC; historic deacetylase inhibitor; HDAC inhibitor; anticancer drug; SAHA; hydroxamic acids; benzo[b]thiophene;

D O I：

10.1016/j.bmcl.2007.05.091

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Benzo[b]thienyl hydroxamic acids, a novel class of historic deacetylase (HDAC) inhibitors, were identified via a targeted screen of small molecule hydroxamic acids. Various substitutions were explored in the C5- and C6-positions of the benzo[b]thiophene core to characterize SAR and develop optimal inhibitors. It was determined that substitution at the C6-position of the benzo[b]thiophene core with a three-atom spacer yielded optimal HDAC I inhibition and anti-proliferative activity in murine erythroleukemia (SC-9) cells. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：4562 / 4567

页数：6

共 22 条

[1]

ABBOTT LABS, 2001, Patent No. 6207701

[2] Synergistic methodologies for the synthesis of 3-aroyl-2-arylbenzo[b]thiophene-based selective estrogen receptor modulators.: Two concise syntheses of raloxifene [J].