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4-(Aminomethyl) benzamides as novel anti-Ebola agents

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R42AI126971-03A1
Agency Tracking Number: R42AI126971
Amount: $2,916,523.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA18-575
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-08-16
Award End Date (Contract End Date): 2022-07-31
Small Business Information
Chicago, IL 60612-3515
United States
DUNS: 079936940
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (312) 355-0203
Business Contact
Phone: (630) 915-4575
Research Institution
CHICAGO, IL 60612-4305
United States

 Nonprofit College or University

Ebola (EBOV) and Marburg (MARV) viruses belong to the Filoviridae family and can cause fatal
hemorrhagic fevers characterized by widespread tissue destruction after an incubation period of
4-14 days. Due to safety concerns, these viruses are designated as biosafety level 4 agents.
Currently, there is no effective vaccine or therapeutic treatment for filoviral infections in humans.
Africa has recently (2014-2016) suffered a lethal EBOV epidemic with 27,000 people infected
and more than11,000 deaths, underscoring the urgency of antiviral drug discovery and
development. This Phase II application proposes to develop potent, small molecule inhibitors,
which block entry of EBOV. We have identified compounds that inhibit entry of infectious
EBOV/MARV with IC50 values in the nanomolar range. In Phase I, we synthesized structurally
diverse analogs of the anti-Ebola CBS1118 hit series based on structure-activity relationships
(SARs), to improve potency and selectivity. Prioritized inhibitors were validated in the infectious
assay. We investigated the mechanism of action (MOA) of selected candidates, and identified
druglike EBOV inhibitors with good in vitro ADME properties. In addition, these inhibitors display
excellent pharmacokinetic parameters in mouse studies, following oral administration. In this
application, we propose to accomplish the following three specific aims: (1) optimize the lead
scaffold and select development candidates; (2) investigate the mechanism of action (MOA) of
the advanced lead compounds with EBOV glycoproteins; and (3) evaluate the in vivo efficacy
and pharmacokinetics/toxicokinetics of the advanced lead compounds.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 anti-Ebola virus

* Information listed above is at the time of submission. *

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