title: Synthesis of novel substituted 2-phenylpyrazolopyridines with potent activity against herpesviruses.
abstract: Herpesviruses are a significant source of human disease; amongst these herpes simplex virus 1 (HSV-1) and HSV-2 are very prevalent and cause recurrent infections. We recently identified a pyrazolo[1,5-a]pyridine scaffold that showed promising activity against HSV-1 and HSV-2 in Vero cell antiviral assays. Here, we describe the synthesis and anti-herpetic activity of several 3-pyrimidinyl-2-phenylpyrazolo[1,5-a]pyridines with differing 2-phenyl substitution patterns. Approaches to rapidly access a number of analogs with different 2-phenyl substitution patterns are outlined. Several of the compounds described have comparable activity to acyclovir against HSV-1 and HSV-2.
authors.affiliation: Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. Kristjan.gudmundsson@gsk.com
authors.forename: Kristjan S
authors.initials: KS
authors.lastname: Gudmundsson
authors.forename: Brian A
authors.initials: BA
authors.lastname: Johns
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Turner
authors.forename: Scott H
authors.initials: SH
authors.lastname: Allen
authors.forename: George A
authors.initials: GA
authors.lastname: Freeman
authors.forename: F Leslie
authors.initials: FL
authors.lastname: Boyd
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Sexton
authors.forename: Dean W
authors.initials: DW
authors.lastname: Selleseth
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Moniri
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Creech
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D018258:Herpesvirus 2, Human / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D019800:Phenol / Q000737:chemistry*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011720:Pyrazoles; D011725:Pyridines; C118531:pyrazolopyridine; D019800:Phenol