Synthesis of C-6 substituted pyrazolo[1,5-a]pyridines with potent activity against herpesviruses.
A novel series of potent C-6 substituted pyrazolo[1,5-a]pyridine inhibitors of herpes simplex viruses has been identified. A synthetic methodology was developed involving functionalization of a C-6 trifluoromethyl pyrazolo[1,5-a]pyridine to allow facile access to a diverse set of analogues from common late stage intermediates. The expansion of the SAR of this series at the 6 position allows for modifications to developability parameters such as clogP, while maintaining potency comparable to acyclovir.
Allen
Scott H
SH
Department of Medicinal Chemistry, GlaxoSmithKline Research and Development, Research Triangle Park, NC 27709, USA. scott.h.allen@gsk.com
Johns
Brian A
BA
Gudmundsson
Kristjan S
KS
Freeman
George A
GA
Boyd
F Leslie
FL
Sexton
Connie H
CH
Selleseth
Dean W
DW
Creech
Katrina L
KL
Moniri
Kelly R
KR
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006564:Herpesviridae / Q000187:drug effects*; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
D011720:Pyrazoles; D011725:Pyridines; C118531:pyrazolopyridine