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.
Babatope Akinbobuyi  1 ,  Lei Wang  2 ,  Katherine C Upchurch  3 ,  Matthew R Byrd  1 ,  Charles A Chang  4 ,  Jeremy M Quintana  1 ,  Rachel E Petersen  1 ,  Zacharie J Seifert  1 ,  José R Boquin  5 ,  SangKon Oh  3 ,  Robert R Kane  6
Affiliations
  • 1. Department of Chemistry and Biochemistry, Baylor University, One Bear Place #97348, Waco, TX 76798, USA.
  • 2. Baylor Institute for Immunology Research, Baylor Research Institute, 3434 Live Oak Street, Dallas, TX 75204, USA.
  • 3. Institute of Biomedical Studies, Baylor University, One Bear Place #97224, Waco, TX 76798, USA; Baylor Institute for Immunology Research, Baylor Research Institute, 3434 Live Oak Street, Dallas, TX 75204, USA.
  • 4. Institute of Biomedical Studies, Baylor University, One Bear Place #97224, Waco, TX 76798, USA.
  • 5. Department of Chemistry, Augustana College, 639 38th Street, Rock Island, IL 61201, USA.
  • 6. Institute of Biomedical Studies, Baylor University, One Bear Place #97224, Waco, TX 76798, USA; Baylor Institute for Immunology Research, Baylor Research Institute, 3434 Live Oak Street, Dallas, TX 75204, USA; Department of Chemistry and Biochemistry, Baylor University, One Bear Place #97348, Waco, TX 76798, USA. Electronic address: [email protected].
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.