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Bioorg Med Chem. 2016 May 1;24(9):2114-24. doi: 10.1016/j.bmc.2016.03.042. Epub 2016 Mar 25.

Design, synthesis, and evaluation of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives as Aurora kinase inhibitors.

Author information

1
College of Pharmacy & Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea.
2
College of Pharmacy & Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea. Electronic address: ryuj@ewha.ac.kr.

Abstract

A series of hinge-binder tethered 1,2,3-triazolylsalicylamide derivatives were designed, synthesized, and evaluated for the Aurora kinase inhibitory activities. The novel hinge-binder tethered 1,2,3-triazolylsalicylamide scaffold was effectively assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC). A variety of alkynes with hinge binders were used to search proper structures-binding relationship to the hinge region. The synthesized 1,2,3-triazolylsalicylamide derivatives showed significant Aurora kinase inhibitory activity. In particular, 8a inhibited Aurora A kinase with an IC50 value of 0.284 μM, whereas 8m inhibited Aurora B kinase with an IC50 value of 0.364 μM.

KEYWORDS:

1,2,3-Triazole; Anticancer; Aurora kinase; Click chemistry; Hinge-binder

PMID:
27041399
DOI:
10.1016/j.bmc.2016.03.042
[Indexed for MEDLINE]

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