Synthesis and biological evaluation of novel thieno[2,3-d]pyrimidine-based FLT3 inhibitors as anti-leukemic agents.

Abstract

The most common mutations in acute myeloid leukemia (AML) are those that cause the activation of FMS-like tyrosine kinase 3 (FLT3). Therefore, FLT3 is regarded as a potential target for the treatment of AML. A novel series of thieno[2,3-d]pyrimidine-based analogs was designed and synthesized as FLT3 inhibitors. All synthesized compounds were assayed for the tyrosine kinase activity of FLT3 and growth inhibitory activity in four human leukemia cell lines (THP1, MV4-11, K562, and HL-60). Among these compounds, compound 17a, which possesses relatively short and simple substituents at the C6 position of thieno[2,3-d]pyrimidine, emerged as the most promising anti-leukemic agent. Compound 17a exhibited potent inhibition of FLT3-positive leukemic cell growth and of the FLT3 D835Y kinase; such inhibition is required for the successful treatment of AML. The data supports the further investigation of this class of compounds as potential anti-leukemic agents.

DOI: 10.1016/j.ejmech.2014.08.001

Cite this paper

@article{Yang2014SynthesisAB, title={Synthesis and biological evaluation of novel thieno[2,3-d]pyrimidine-based FLT3 inhibitors as anti-leukemic agents.}, author={Jee Sun Yang and Chun-Ho Park and C. Justin Lee and Hwan Mook Kim and Changmok Oh and Yejoo Choi and Jong Soon Kang and Jieun Yun and Jin-Hyun Jeong and Myung-Hwa Kim and Gyoonhee Han}, journal={European journal of medicinal chemistry}, year={2014}, volume={85}, pages={399-407} }