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Synthesis and biological evaluation of N9-cis-cyclobutylpurine derivatives for use as cyclin-dependent kinase (CDK) inhibitors.

Abstract：

:A novel 6-aminopurine scaffold bearing an N9-cis-cyclobutyl moiety was designed using structure-based molecular design based on two known CDK inhibitors, dinaciclib and Cmpd-27. A series of novel 6-aminopurine compounds was prepared for structure-activity relationship (SAR) studies of CDK2 and CDK5 inhibitors. Among the compounds synthesized, compound 8l displayed potent CDK2 and CDK5 inhibitory activities with low nanomolar ranges (IC50=2.1 and 4.8nM, respectively) and showed moderate cytotoxicity in HCT116 colon cancer and MCF7 breast cancer cell lines. Here, we report the synthesis and evaluation of novel 6-aminopurine derivatives and present molecular docking models of compound 81 with CDK2 and CDK5.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Park SJ,Kim E,Yoo M,Lee JY,Park CH,Hwang JY,Ha JD

doi

10.1016/j.bmcl.2017.08.018

subject

Has Abstract

pub_date

2017-09-15 00:00:00

pages

4399-4404

issue

18

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(17)30820-X

journal_volume

27

pub_type

杂志文章

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