Synthesis of quinolinylaminopyrimidines and quinazolinylmethylaminopyrimidines with antiproliferative activity against melanoma cell line

Abstract

Synthesis of a new series of quinolinylaminopyrimidines 1a–k and quinazolinylmethylaminopyrimidines 2a–i containing aminoquinoline and aminoquinazoline as hinge regions is described. Their in vitro antiproliferative activities against A375P human melanoma cell line were tested. Among them, compounds 1h and 1k exhibited the highest antiproliferative activities against A375P cell line with IC₅₀ values in sub-micromolar scale. Compounds 1i, 2b and 2g showed similar potency against A375P to Sorafenib as a reference compound. The representative compound 1h showed high, dose-dependent inhibition of MEK and ERK kinases.

• Antiproliferative
• MEK/ERK kinase inhibition
• melanoma cell line
• quinazoline
• quinoline

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was funded by the KIST Institutional Program (Grant No. 2E24760) from Korea Institute of Science and Technology, and by the Creative Fusion Research Program (Grant No. CAP-12-1) from Korea Research Council of Fundamental Science and Technology.

Supplementary material available online