906352-88-3Relevant academic research and scientific papers
Discovery of Novel Small Molecule Dual Inhibitors Targeting Toll-Like Receptors 7 and 8
Padilla-Salinas, Rosaura,Anderson, Rachel,Sakaniwa, Kentaro,Zhang, Shuting,Nordeen, Patrick,Lu, Chuanjun,Shimizu, Toshiyuki,Yin, Hang
, p. 10221 - 10244 (2019)
Endosomal toll-like receptors (TLRs) 7 and 8 recognize viral single-stranded RNAs, a class of imidazoquinoline compounds, 8-oxo-adenosines, 8-aminobenzodiazepines, pyrimidines, and guanosine analogues. Substantial evidence is present linking chronic inflammation mediated specifically by TLR7 to the progression of autoimmunity. We identified a new TLR7/8 dual inhibitor (1) and a TLR8-specific inhibitor (2) based on our previous screen targeting TLR8. Compound 1, bearing a benzanilide scaffold, was found to inhibit TLR7 and TLR8 at low micromolar concentrations. We envisioned making modifications on the benzanilide scaffold of 1 resulting in a class of highly specific TLR7 inhibitors. Our efforts led to the discovery of a new TLR8 inhibitor (CU-115) and identification of a TLR7/8 dual inhibitor (CU-72), bearing a distinct diphenyl ether skeleton, with potential for TLR7 selectivity optimization. Given the role of TLR8 in autoimmunity, we also optimized the potency of 2 and developed a new TLR8 inhibitor bearing a 1,3,4-oxadiazole motif.
NOVEL PIPERAZINE ANALOGS AS BROAD-SPECTRUM INFLUENZA ANTIVIRALS
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Page/Page column 64, (2012/03/27)
A compound of Formula (I) is set forth, including pharmaceutically acceptable salts thereof, wherein Het is a 5 or 6-membered heterocycle with -N, -O, or -S adjacent to the -Ar substituent or adjacent to the point of attachment for the -Ar substituent; Ar
