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

Information

  • Research Project
  • 9321915
  • ApplicationId
    9321915
  • Core Project Number
    R41AI126971
  • Full Project Number
    5R41AI126971-02
  • Serial Number
    126971
  • FOA Number
    PA-15-270
  • Sub Project Id
  • Project Start Date
    8/1/2016 - 8 years ago
  • Project End Date
    7/31/2018 - 6 years ago
  • Program Officer Name
    DEMPSEY, WALLA L.
  • Budget Start Date
    8/1/2017 - 7 years ago
  • Budget End Date
    7/31/2018 - 6 years ago
  • Fiscal Year
    2017
  • Support Year
    02
  • Suffix
  • Award Notice Date
    7/11/2017 - 7 years ago

4-(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 4-14 days. Because of the safety concerns, these viruses are designated as the biosafety level 4 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 ~27,000 people infected and ~11,000 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 (IC50 values ?10 µM). 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: (1) Synthesize structurally diverse analogs of the anti-Ebola CBS1118 hit series based on structure-activity relationships (SARs) to improve potency and selectivity. (2) Validate the lead inhibitor candidates in the infectious assay and investigate the mechanism of action (MOA) of the EBOV inhibitors. (3) Select EBOV inhibitors with in vitro ADME properties suitable for i.v. and oral dosing.

IC Name
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
  • Activity
    R41
  • Administering IC
    AI
  • Application Type
    5
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    363598
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    855
  • Ed Inst. Type
  • Funding ICs
    NIAID:363598\
  • Funding Mechanism
    SBIR-STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    CHICAGO BIOSOLUTIONS, INC.
  • Organization Department
  • Organization DUNS
    079936940
  • Organization City
    CHICAGO
  • Organization State
    IL
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    606123515
  • Organization District
    UNITED STATES