2. Academic Validation
  3. C-2 (E)-4-(Styryl)aniline substituted diphenylpyrimidine derivatives (Sty-DPPYs) as specific kinase inhibitors targeting clinical resistance related EGFRT790M mutant

C-2 (E)-4-(Styryl)aniline substituted diphenylpyrimidine derivatives (Sty-DPPYs) as specific kinase inhibitors targeting clinical resistance related EGFRT790M mutant

  • Bioorg Med Chem. 2017 May 15;25(10):2724-2729. doi: 10.1016/j.bmc.2017.03.032.
Anran Song 1,  Jianbin Zhang 1,  Yang Ge 1,  Changyuan Wang 1,  Qiang Meng 1,  Zeyao Tang 1,  Jinyong Peng 1,  Kexin Liu 1,  Yanxia Li 2,  Xiaodong Ma 3
Affiliations

Affiliations

  • 1 College of Pharmacy, Dalian Medical University, Dalian 116044, PR China.
  • 2 Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China.
  • 3 College of Pharmacy, Dalian Medical University, Dalian 116044, PR China. Electronic address: xiaodong.ma@139.com.
PMID: 28385595 DOI: 10.1016/j.bmc.2017.03.032
Abstract

With the aim to overcome the drug resistance induced by the EGFR T790M mutation (EGFRT790M), herein, a family of diphenylpyrimidine derivatives (Sty-DPPYs) bearing a C-2 (E)-4-(styryl)aniline functionality were designed and synthesized as potential EGFRT790M inhibitors. Among them, the compound 10e displayed strong potency against the EGFRT790M Enzyme, with the IC50 of 11.0nM. Compound 10e also showed a higher SI value (SI=49.0) than rociletinib (SI=21.4), indicating its less side effect. In addition, compound 10e could effectively inhibit the proliferation of H1975 cells harboring the EGFRT790M mutation, within the concentration of 2.91μM. Significantly, compound 10e has low toxicity against the normal HBE cell (IC50=22.48μM). This work provided new insights into the discovery of potent and selective inhibitor against EGFRT790M over wild-type (EGFRWT).

Keywords

Diphenylpyrimidine; EGFR(T790M); Inhibitor; NSCLC; Resistance.

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