Discovery of Novel Thieno[2,3-d]pyrimidin-4-yl Hydrazone-Based Cyclin-Dependent Kinase 4 Inhibitors: Synthesis, Biological Evaluation and Structure-Activity Relationships

Abstract

The design, synthesis, and evaluation of novel thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as cyclin-dependent kinase 4 (CDK4) inhibitors are described. In continuing our program aim to search for potent CDK4 inhibitors, the introduction of a thiazole group at the hydrazone part has led to marked enhancement of chemical stability. Furthermore, by focusing on the optimization at the C-4′ position of the thiazole ring and the C-6 position of the thieno[2,3-d]pyrimidine moiety, compound 35 has been identified with efficacy in a xenograft model of HCT116 cells. In this paper, the potency, selectivity profile, and structure–activity relationships of our synthetic compounds are discussed.

Journal

Chemical and Pharmaceutical Bulletin  

Chemical and Pharmaceutical Bulletin 59(8), 991-1002, 2011 

The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID) :
    130000960931
  • NII NACSIS-CAT ID (NCID) :
    AA00602100
  • Text Lang :
    EN
  • ISSN :
    0009-2363
  • NDL Article ID :
    11174305
  • NDL Source Classification :
    ZS51(科学技術--薬学) // ZP1(科学技術--化学・化学工業)
  • NDL Call No. :
    Z53-D167
  • Databases :
    NDL  J-STAGE 

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