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Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold.

Abstract：

:Both histone deacetylase (HDAC) and fibroblast growth factor receptor (FGFR) are important targets for cancer therapy. Although combining dual HDAC pharmacophore with tyrosine kinase inhibitors (TKIs) had achieved a successful progress, dual HDAC/FGFR1 inhibitors haven't been reported yet. Herein, we designed a series of hybrids bearing 1H-indazol-3-amine and benzohydroxamic acids scaffold with scaffold hopping and molecular hybridization strategies. Among them, compound 7j showed the most potent inhibitory activity against HDAC6 with IC50 of 34 nM and exhibited the great inhibitory activities against a human breast cancer cell line MCF-7 with IC50 of 9 μM in vitro. Meanwhile, the compound also exhibited moderate FGFR1 inhibitory activities. This study provides new tool compounds for further exploration of dual HDAC/FGFR1 inhibition.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Liu J,Qian C,Zhu Y,Cai J,He Y,Li J,Wang T,Zhu H,Li Z,Li W,Hu L

doi

10.1016/j.bmc.2017.12.041

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

747-757

issue

3

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(17)32183-1

journal_volume

26

pub_type

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