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Author Notes:

Correspondence: Aiming Sun; Phone: 404-712-8680; Fax: 404-727-6689; E-mail: asun2@emory.edu

Acknowledgments: Guest Editor: J. Aubé

We also thank Deborah Culver for solubility testing and Dr. John Bacsa for helpful discussions of crystal structures.

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Research Funding:

This work was supported, in part, by Public Health Service Grants AI071002 and AI085328 (to R. K. P.) from the NIH/ NIAID and by Public Health Service Grant HG003918-02 (to J.P.S.) from the NIH.

Keywords:

  • asymmetric synthesis
  • benzimidazole
  • host-directed
  • myxovirus
  • small molecule inhibitor

Asymmetric synthesis of host-directed inhibitors of myxoviruses

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Journal Title:

Beilstein Journal of Organic Chemistry

Volume:

Volume 2013, Number 9

Publisher:

, Pages 197-203

Type of Work:

Article | Final Publisher PDF

Abstract:

High-throughput screening (HTS) previously identified benzimidazole 1 (JMN3-003) as a compound with broad antiviral activity against different influenza viruses and paramyxovirus strains. In pursuit of a lead compound from this series for development, we sought to increase both the potency and the aqueous solubility of 1. Lead optimization has achieved compounds with potent antiviral activity against a panel of myxovirus family members (EC50 values in the low nanomolar range) and much improved aqueous solubilities relative to that of 1. Additionally, we have devised a robust synthetic strategy for preparing 1 and congeners in an enantio-enriched fashion, which has allowed us to demonstrate that the (S)-enantiomers are generally 7- to 110-fold more potent than the corresponding (R)-isomers.

Copyright information:

© 2013 Moore et al; licensee Beilstein-Institut.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).

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