Exploring the connection unit in the HDAC inhibitor pharmacophore model: Novel uracil-based hydroxamates

被引：44

作者：

Mai, A

Mass, S

Rotili, D

Pezzi, R

Bottoni, P

Scatena, R

Meraner, J

Brosch, G

机构：

[1] Univ Roma La Sapienza, Ist Pasteur, Fdn Cenci Bolognetti, Dipartimento Studi Farmaceut, I-00185 Rome, Italy

[2] Univ Siena, Dipartimento Farm Chim Technol, I-53100 Siena, Italy

[3] Univ Cattolica Sacro Cuore, Ist Biochim & Biochim Clin, I-00168 Rome, Italy

[4] Innsbruck Med Univ, Bioctr, Div Mol Biol, A-6020 Innsbruck, Austria

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 21期

关键词：

D O I：

10.1016/j.bmcl.2005.07.081

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from the pharmacophore model for HDAC inhibitor design, a novel series of hydroxamates bearing a uracil moiety as connecting unit (CU) has been prepared and tested. Almost all compounds exhibited HDAC inhibiting activity at low nanomolar concentrations, the N-hydroxy-6-(3,4-dihydro-4-oxo-6-benzyl- and -6-phenyl-2-pyrimidinylthio)hexanamides 1d and 11 being more potent than SAHA in enzymatic assays. Such compounds also caused hyperacetylation in NIH3T3 cell core histones and were endowed with interesting antiproliferative and cytodifferentiating effects in human leukemia (HL-60) cells. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：4656 / 4661

页数：6

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