title: Design and optimisation of orally active TLR7 agonists for the treatment of hepatitis C virus infection.
abstract: The synthesis and structure-activity relationships of a series of novel interferon inducers are described. Pharmacokinetic studies and efficacy assessment of a series of 8-oxo-3-deazapurine analogues led to the identification of compound 33, a potent and selective agonist of the TLR7 receptor with an excellent in vivo efficacy profile in a mouse model.
authors.affiliation: Discovery Chemistry, Dynamics and Metabolism, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK. thien.tran@pfizer.com
authors.forename: Thien-Duc
authors.initials: TD
authors.lastname: Tran
authors.forename: David C
authors.initials: DC
authors.lastname: Pryde
authors.forename: Peter
authors.initials: P
authors.lastname: Jones
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Adam
authors.forename: Neil
authors.initials: N
authors.lastname: Benson
authors.forename: Gerwyn
authors.initials: G
authors.lastname: Bish
authors.forename: Frederick
authors.initials: F
authors.lastname: Calo
authors.forename: Guiseppe
authors.initials: G
authors.lastname: Ciaramella
authors.forename: Rachel
authors.initials: R
authors.lastname: Dixon
authors.forename: Jonathan
authors.initials: J
authors.lastname: Duckworth
authors.forename: David N A
authors.initials: DN
authors.lastname: Fox
authors.forename: Duncan A
authors.initials: DA
authors.lastname: Hay
authors.forename: James
authors.initials: J
authors.lastname: Hitchin
authors.forename: Nigel
authors.initials: N
authors.lastname: Horscroft
authors.forename: Martin
authors.initials: M
authors.lastname: Howard
authors.forename: Iain
authors.initials: I
authors.lastname: Gardner
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Jones
authors.forename: Carl
authors.initials: C
authors.lastname: Laxton
authors.forename: Tanya
authors.initials: T
authors.lastname: Parkinson
authors.forename: Gemma
authors.initials: G
authors.lastname: Parsons
authors.forename: Katie
authors.initials: K
authors.lastname: Proctor
authors.forename: Mya C
authors.initials: MC
authors.lastname: Smith
authors.forename: Nicholas
authors.initials: N
authors.lastname: Smith
authors.forename: Amy
authors.initials: A
authors.lastname: Thomas
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D015195:Drug Design; D016174:Hepacivirus / Q000187:drug effects*; D051379:Mice; D023421:Models, Animal; D011687:Purines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012327:RNA Virus Infections / Q000188:drug therapy*; D051381:Rats; D013329:Structure-Activity Relationship; D051199:Toll-Like Receptor 7 / Q000819:agonists* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D011687:Purines; D051199:Toll-Like Receptor 7