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Aminopiperidines as novel anti influenza agents

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI127031-01
Agency Tracking Number: R41AI127031
Amount: $396,096.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA15-270
Solicitation Year: 2015
Award Year: 2016
Award Start Date (Proposal Award Date): 2016-06-01
Award End Date (Contract End Date): 2019-05-31
Small Business Information
2242 WEST HARRISON SUITE 201, Chicago, IL, 60612-3515
DUNS: 079936940
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (312) 355-0203
Business Contact
Phone: (630) 915-4575
Research Institution
 1737 W POLK ST STE 310
CHICAGO, IL, 60612-7224
 Nonprofit college or university
Influenza A viruses belong to the orthomyxoviridae family with a negative sense segmented RNA genome which can cause seasonal or pandemic flu with high morbidity and significant mortality Vaccination is the most prevalent prophylactic means for controlling influenza infections However an effective vaccine usually takes at least months to develop for the circulating strains Furthermore vaccination has limited effectiveness in treatment of immunocompromised patients and its effectiveness is also limited during a pandemic The current therapeutic options for flu infections are all based on the NA inhibitors NAIs while the influenza M ion channel blockers amantadine and rimantadine are not recommended anymore since all the circulating influenza strains are resistant to them However the rapid emergence of the NAI resistant strains of influenza A viruses strongly suggest that NAIs alone may not be sufficient as an effective means of the anti flu therapies and thus new treatment options targeting the other viral host factors are urgently needed This application defines a plan to develop potent small molecule inhibitors which block entry of influenza A viruses We have identified compounds that inhibit entry of infectious influenza A viruses IC values M These hit compounds exhibit selectivity for H N and H N entry The overall objective of this Phase I application is to develop these inhibitors as potential anti flu therapeutics This application will focus on the following three specific aims Synthesize structurally diverse analogs of the anti flu 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 inhibitors Select flu 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 influenza viral infection The proposed research will help to develop potential antiviral therapeutics

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

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