Aminomethyl benzamides as novel anti Ebola agents

Ebola EBOV and Marburg MARV viruses belong to the family Filoviridae and can
cause fatal hemorrhagic fevers characterized by widespread tissue destruction with an
incubation period of days Because of the safety concerns these viruses are
designated as the biosafety level agents Currently there is no effective vaccine or
therapeutic treatment against filoviral infection and pathogenesis in humans Africa has
recently suffered a lethal EBOV epidemic with people infected and
deaths underscoring the urgency of antiviral drug discovery and development This
application defines a plan to develop potent small molecule inhibitors which block entry
of EBOV We have identified compounds that inhibit entry of infectious EBOV MARV
IC values M These hit compounds exhibit selectivity for EBOV MARV entry
The overall objective of this Phase I application is to develop these inhibitors as potential
anti EBOV therapeutics This application will focus on the following three specific aims
Synthesize structurally diverse analogs of the anti Ebola CBS hit series based
on structure activity relationships SARs to improve potency and selectivity Validate
the lead inhibitor candidates in the infectious assay and investigate the mechanism of
action MOA of the EBOV inhibitors Select EBOV inhibitors with in vitro ADME
properties suitable for i v and oral dosing Project Narrative
This project is to discover and develop small molecule entry inhibitors for Ebola viral
infection The proposed research will help to develop potential antiviral therapeutics