Synthesis of N-Heteroaroyl Aminosaccharide Derivatives as Fibroblast Growth Factor 2 Signaling Modulators

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  • Dong Jin
    Department of Medicinal Chemistry, China Pharmaceutical University
  • Yao Shuowei
    Department of Medicinal Chemistry, China Pharmaceutical University
  • Zhou Xiaodong
    Department of Pathology and Immunology, Washington University School of Medicine
  • Zhang Lijuan
    Department of Pathology and Immunology, Washington University School of Medicine
  • Xu Yungen
    Department of Medicinal Chemistry, China Pharmaceutical University

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Fibroblast growth factor 2 (FGF2) signaling plays an important role in angiogenesis. Heparin/heparan sulfate (HS) is required for FGF2 signaling but heparin mimics either promotes or inhibits FGF2 signaling. To take advantage such properties of heparin mimics, a series of N-heteroaroyl aminosaccharide derivatives were designed and synthesized as FGF2 signaling modulators. The bioactivity was determined in a FGF2 and heparin-dependent cell proliferation assay using FGFR1c expressing BaF3 cells. We found that most of the compounds inhibited heparin- and FGF2-dependent BaF3 cell proliferation while three compounds promoted the cell proliferation. These results suggest that the small molecular heparin mimics approach might be useful in developing novel anti-angiogenic agents.

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