Synthesis of novel substituted 2-phenylpyrazolopyridines with potent activity against herpesviruses.
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.
Gudmundsson
Kristjan S
KS
Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. Kristjan.gudmundsson@gsk.com
Johns
Brian A
BA
Wang
Zhicheng
Z
Turner
Elizabeth M
EM
Allen
Scott H
SH
Freeman
George A
GA
Boyd
F Leslie
FL
Sexton
Connie J
CJ
Selleseth
Dean W
DW
Moniri
Kelly R
KR
Creech
Katrina L
KL
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
D000998:Antiviral Agents; D011720:Pyrazoles; D011725:Pyridines; C118531:pyrazolopyridine; D019800:Phenol