Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine derivatives as c-Met inhibitors.

Abstract:

:Five novel 1H-pyrrolo[2,3-b]pyridine or 1H-pyrazolo[3,4-b]pyridine derivatives, with a methylene, sulfur, sulfoxide or cyclopropyl group as a linker, were designed, synthesized and biologically evaluated against c-Met and ALK. The development of these methods of compound synthesis may provide an important reference for the construction of novel 7-azaindole and 7-azaindazole derivatives with a single atom linker. The enzyme assay and cell assay in vitro showed that compound 9 displayed strong c-Met kinase inhibition with IC50 of 22.8nM, moderate ALK kinase inhibition, and strong cell inhibition with MKN-45 IC50 of 329nM and EBC-1 IC50 of 479nM. In order to find the better candidate compounds, compounds 8, 9 and 10 have been selected as tool compounds for further optimization.

journal_name

Bioorg Chem

journal_title

Bioorganic chemistry

authors

Liu N,Wang Y,Huang G,Ji C,Fan W,Li H,Cheng Y,Tian H

doi

10.1016/j.bioorg.2016.02.009

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

146-58

eissn

0045-2068

issn

1090-2120

pii

S0045-2068(16)30018-9

journal_volume

65

pub_type

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