Open AccessSynthesis, structure-activity relationship studies and evaluation of a TLR 3/8/9 agonist and its analogues
Author(s) -
Anindya Sarkar,
Anushka C. Galasiti Kankanamalage,
Qian Zhang,
Heng Cheng,
Prasanna Sivaprakasam,
Joseph G. Naglich,
Chunshan Xie,
Sanjeev Gangwar,
Dale L. Boger
Publication year - 2021
Publication title -
medicinal chemistry research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.352
H-Index - 45
eISSN - 1554-8120
pISSN - 1054-2523
DOI - 10.1007/s00044-021-02736-3
Subject(s) - agonist , chemistry , intrinsic activity , potency , pharmacology , partial agonist , ec50 , structure–activity relationship , stereochemistry , receptor , in vitro , biochemistry , medicine
A comprehensive SAR study of a putative TLR 3/8/9 agonist was conducted. Despite the excitement surrounding the potential of the first small molecule TLR3 agonist with a compound that additionally displayed agonist activity for TLR8 and TLR9, compound 1 displayed disappointing activity in our hands, failing to match the potency (EC 50 ) reported and displaying only a low efficacy for the extent of stimulated NF-κB activation and release. The evaluation of >75 analogs of 1 , many of which constitute minor modifications in the structure, failed to identify any that displayed significant activity and none that exceeded the modest activity found for 1 .