Histone deacetylase inhibitors derived from 1,2,3,4-tetrahydropyrrolo[1,2-a] pyrazine and related heterocycles selective for the HDAC6 isoform

被引：12

作者：

Blackburn, Christopher ^{[1
]}

Barrett, Cynthia ^{[1
]}

Brunson, Mable ^{[1
]}

Chin, Janice ^{[1
]}

England, Dylan ^{[1
]}

Garcia, Kris ^{[1
]}

Gigstad, Kenneth ^{[1
]}

Gould, Alexandra ^{[1
]}

Gutierrez, Juan ^{[1
]}

Hoar, Kara ^{[1
]}

Rowland, R. Scott ^{[1
]}

Tsu, Christopher ^{[1
]}

Ringeling, John ^{[1
]}

Wager, Krista ^{[1
]}

Xu, He ^{[1
]}

机构：

[1] Takeda Pharmaceut Int Co, Discovery, Cambridge, MA 02139 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 23期

关键词：

Histone deacetylase; HDAC6; selective; Hydroxamic acid; Acetyl tubulin; ZINC-BINDING; PROTEASOME; CHEMISTRY; AUTOPHAGY; PATHWAY; DESIGN; CANCER; POTENT; DOMAIN;

D O I：

10.1016/j.bmcl.2014.10.022

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Acyl derivatives of 4-(aminomethyl)-N-hydroxybenzamide are potent sub-type selective HDAC6 inhibitors. Constrained heterocyclic analogs based on 1,2,3,4-tetrahydropyrrolo[1,2-a] pyrazine show further enhanced HDAC6 selectivity and inhibitory activity in cells. Homology models suggest that the heterocyclic spacer can more effectively access the wider catalytic channel of HDAC6 compared to other HDAC sub-types. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：5450 / 5454

页数：5

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