1449680-40-3Relevant academic research and scientific papers
TOLL-LIKE RECEPTOR 8 AGONISTS
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Page/Page column 23-24; 41; 24; 42, (2015/07/07)
Compounds described herein can be used for therapeutic purposes. The compounds can be TLR agonists, such as TLR8 agonists. The compounds can be included in pharmaceutical compositions and used for therapies were being a TLR8 agonist is useful. The pharmac
Exquisite selectivity for human toll-like receptor 8 in substituted furo[2,3-c]quinolines
Kokatla, Hari Prasad,Sil, Diptesh,Malladi, Subbalakshmi S.,Balakrishna, Rajalakshmi,Hermanson, Alec R.,Fox, Lauren M.,Wang, Xinkun,Dixit, Anshuman,David, Sunil A.
, p. 6871 - 6885 (2013/10/01)
Toll-like receptor (TLR)-8 agonists activate adaptive immune responses by inducing robust production of T helper 1-polarizing cytokines, suggesting that TLR8-active compounds may be promising candidate adjuvants. We synthesized and evaluated hitherto unexplored furo[2,3-c]quinolines and regioisomeric furo[3,2-c]quinolines derived via a tandem, one-pot Sonogashira coupling and intramolecular 5-endo-dig cyclization strategy in a panel of primary screens. We observed a pure TLR8-agonistic activity profile in select furo[2,3-c] quinolines, with maximal potency conferred by a C2-butyl group (EC50 = 1.6 μM); shorter, longer, or substituted homologues as well as compounds bearing C1 substitutions were inactive, which was rationalized by docking studies using the recently described crystal structure of human TLR8. The best-in-class compound displayed prominent proinflammatory cytokine induction (including interleukin-12 and interleukin-18), but was bereft of interferon-α inducing properties, confirming its high selectivity for human TLR8.
