Pyrazolopyridine antiherpetics: SAR of C2' and C7 amine substituents.
A novel series of potent pyrazolo[1,5-a]pyridine inhibitors of herpes simplex virus 1 replication have been identified. Several complimentary synthetic methods were developed to allow facile access to a diverse set of analogs from common late stage intermediates. Detailed examination of the amine substituents at the C2' position of the pyrimidine and C7 position of the core pyrazolopyridine is described. The antiviral data suggests that non-polar amines are preferred for optimal activity. Additionally, the 2' position has been shown to require an NH group to retain activity levels similar to that of the gold standard acyclovir.
Johns
Brian A
BA
Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. brian.a.johns@gsk.com <brian.a.johns@gsk.com>
Gudmundsson
Kristjan S
KS
Turner
Elizabeth M
EM
Allen
Scott H
SH
Samano
Vicente A
VA
Ray
John A
JA
Freeman
George A
GA
Boyd
F Leslie
FL
Sexton
Connie J
CJ
Selleseth
Dean W
DW
Creech
Katrina L
KL
Moniri
Kelly R
KR
D000588:Amines / Q000737:chemistry*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D006564:Herpesviridae / Q000187:drug effects; D006568:Herpesvirus 1, Cercopithecine / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; 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
D000588:Amines; D000998:Antiviral Agents; D011720:Pyrazoles; D011725:Pyridines