title: Discovery of ANA975: an oral prodrug of the TLR-7 agonist isatoribine.
abstract: ANA975, a 5-amino-3-beta -D-ribofuranosyl-3H-thiazolo[4,5-d]pyrimidin-2-one derivative, was synthesized in the search of an oral prodrug of isatoribine, a small molecule toll-like receptor 7 (TLR-7) agonist. Several strategies were studied to enable the kilogram-scale synthesis of ANA975. Three general total syntheses are described. In the phase I clinical study of ANA975 against hepatitis C virus (HCV), conversion to isatoribine in plasma was rapid and effective, delivering levels of isatoribine that have been shown to be clinically relevant.
authors: Anadys Pharmaceuticals, Inc., San Diego, California 92121, USA. axiang@anadyspharma.com
authors: Alan X
authors: AX
authors: Xiang
authors: Stephen E
authors: SE
authors: Webber
authors: Bradley M
authors: BM
authors: Kerr
authors: Erik J
authors: EJ
authors: Rueden
authors: Joseph R
authors: JR
authors: Lennox
authors: Gregory J
authors: GJ
authors: Haley
authors: Tingmin
authors: T
authors: Wang
authors: John S
authors: JS
authors: Ng
authors: Mark R
authors: MR
authors: Herbert
authors: David L
authors: DL
authors: Clark
authors: Virginia N
authors: VN
authors: Banh
authors: Wei
authors: W
authors: Li
authors: Simon P
authors: SP
authors: Fletcher
authors: Kevin R
authors: KR
authors: Steffy
authors: Darian M
authors: DM
authors: Bartkowski
authors: Leonid I
authors: LI
authors: Kirkovsky
authors: Lisa A
authors: LA
authors: Bauman
authors: Devron R
authors: DR
authors: Averett
mesh_terms: D000284:Administration, Oral; D000998:Antiviral Agents / Q000494:pharmacology; D015195:Drug Design; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D011355:Prodrugs / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051199:Toll-Like Receptor 7 / Q000819:agonists*
chemical_list: D000998:Antiviral Agents; D011355:Prodrugs; D011744:Pyrimidinones; D051199:Toll-Like Receptor 7; D006151:Guanosine; C061136:isatoribine