| Literature DB >> 28671847 |
David C McGowan1, Florence Herschke1, Frederik Pauwels1, Bart Stoops1, Ilham Smyej1, Stefaan Last1, Serge Pieters1, Werner Embrechts1, Mourad Daoubi Khamlichi2, Tine Thoné1, Bertrand Van Schoubroeck1, Wendy Mostmans1, Debbie Wuyts1, Dorien Verstappen1, Annick Scholliers1, Dorien De Pooter1, Deborah Dhuyvetter1, Herman Borghys1, Marianne Tuefferd1, Eric Arnoult3, Jin Hong4, Gregory Fanning1, Jacques Bollekens1, Vijay Urmaliya1, Ard Teisman1, Helen Horton1, Tim H M Jonckers1, Pierre Raboisson1.
Abstract
Pyrrolo[3,2-d]pyrimidines were identified as a new series of potent and selective TLR7 agonists. Compounds were optimized for their activity and selectivity over TLR8. This presents an advantage over recently described scaffolds that have residual TLR8 activity, which may be detrimental to the tolerability of the candidate drug. Oral administration of the lead compound 54 effectively induced a transient interferon stimulated gene (ISG) response in mice and cynomolgus monkeys. We aimed for a high first pass effect, limiting cytokine induction systemically, and demonstrated the potential for the immunotherapy of viral hepatitis.Entities:
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Year: 2017 PMID： 28671847 DOI： 10.1021/acs.jmedchem.7b00365
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446