Synthesis of C-6 substituted pyrazolo[1,5-a]pyridines with potent activity against herpesviruses

Abstract 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 clog  P , while maintaining potency comparable to acyclovir.