Abstract
We designed a series of 2-methylpyrimidine derivatives as new BCR-ABL inhibitors using scaffold-hopping strategy. These synthetic compounds exhibited significant inhibition against a broad spectrum of Bcr-Abl mutants including the gatekeeper T315I mutant. Compound 7u showed very potent kinase inhibitory activities against Bcr-Abl WT, Bcr-Abl E255K, Bcr-Abl Q252H, Bcr-Abl G250E and Bcr-Abl T315I, with IC50 values of 0.13 nM, 0.17 nM, 0.24 nM, 0.19 nM and 0.65 μM, respectively. This compound also displayed anti-proliferation activity against K562 cell line with an IC50 value of 1.1 nM, thus representing a new lead for further optimization.
Original language | English (US) |
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Pages (from-to) | 823-832 |
Number of pages | 10 |
Journal | Science China Chemistry |
Volume | 57 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2014 |
Keywords
- anticancer agents
- Bcr-Abl
- chronic myeloid leukemia (CML)
- imatinib resistance
ASJC Scopus subject areas
- Chemistry(all)