Synthesis and immunostimulatory activity of substituted TLR7 agonists

Bioorg Med Chem Lett. 2016 Sep 1;26(17):4246-9. doi: 10.1016/j.bmcl.2016.07.049. Epub 2016 Jul 22.

Abstract

Fifteen new substituted adenines were synthesized as potential TLR7 agonists. These compounds, along with 9 previously reported compounds, were analyzed for TLR7 activity and for the selective stimulation of B cell proliferation. Several functionalized derivatives exhibit significant activity, suggesting their potential for use as vaccine adjuvants.

Keywords: Adenine derivatives; Immune activation; Toll-like receptor; Vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / chemical synthesis
  • Adenine / pharmacology
  • Adjuvants, Immunologic / chemical synthesis*
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology
  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Crystallography, X-Ray
  • Humans
  • Lymphocyte Activation / drug effects
  • Molecular Conformation
  • Toll-Like Receptor 7 / agonists*
  • Toll-Like Receptor 7 / metabolism

Substances

  • Adjuvants, Immunologic
  • Amides
  • Toll-Like Receptor 7
  • Adenine