Synthesis and immunostimulatory activity of substituted TLR7 agonists

Babatope Akinbobuyi; Lei Wang; Katherine C Upchurch; Matthew R Byrd; Charles A Chang; Jeremy M Quintana; Rachel E Petersen; Zacharie J Seifert; José R Boquin; SangKon Oh; Robert R Kane

doi:10.1016/j.bmcl.2016.07.049

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.

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: bob_kane@baylor.edu.

PMID: 27476423
DOI: 10.1016/j.bmcl.2016.07.049

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