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

Award Number: R42AI126971
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/07/2016
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2021	CHICAGO BIOSOLUTIONS INC	2242 W HARRISON ST	CHICAGO	IL	60612	COOK	USA	Allergy and Infectious Diseases Research	000	5	2/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	CHICAGO BIOSOLUTIONS INC	2242 W HARRISON ST	CHICAGO	IL	60612	COOK	USA	Allergy and Infectious Diseases Research	000	5	7/21/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $982,388 )
2021	2021	CHICAGO BIOSOLUTIONS, INC.	2242 WEST HARRISON SUITE 201	CHICAGO	IL	60612	COOK	USA	Allergy and Infectious Diseases Research	000	5	7/14/2021	NON-COMPETING CONTINUATION	$982,388
														Subtotal = $982,388

Issue Date FY: 2020 ( Subtotal = $961,660 )
2020	2020	CHICAGO BIOSOLUTIONS, INC.	2242 WEST HARRISON SUITE 201	CHICAGO	IL	60612	COOK	USA	Allergy and Infectious Diseases Research	000	4	7/1/2020	NON-COMPETING CONTINUATION	$961,660
														Subtotal = $961,660

Issue Date FY: 2019 ( Subtotal = $972,475 )
2019	2019	CHICAGO BIOSOLUTIONS, INC.	2242 WEST HARRISON SUITE 201	CHICAGO	IL	60612	COOK	USA	Allergy and Infectious Diseases Research	000	3	8/16/2019	COMPETING CONTINUATION	$972,475
														Subtotal = $972,475

Grand Total All Awards = $2,916,523

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

Award Number: R42AI126971

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/07/2016

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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