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Anti-Viral Compounds that Inhibit HIV Activity

Summary
The National Cancer Institute (NCI) Molecular Targets Laboratory is seeking parties interested in collaborative research to co-develop antiviral tropolone derivatives developed by systematic medicinal chemistry on the lead series.
NIH Reference Number
E-081-2011
Product Type
Keywords
  • HIV
  • AIDS, RNase H
  • tropolone derivative
  • ribonuclease H
  • viral replication
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

Several novel tropolone derivatives have been identified that inhibit HIV-1 RNase H function and have potential for anti-viral activity due to reduced cellular toxicity.  Inhibiting RNase H function is a potential treatment for many viral infections, since RNase H function is essential for viral replication for many pathogenic retroviruses such as HIV-1 and HIV-2.  Although many hydroxytropolone compounds are potent RNase H inhibitors biding at the enzymatic active site, they are limited as therapeutic candidates by their toxicity in mammalian cells.  The toxicity thought to be a result of inhibition of multiple essential mammalian metalloenzymes.  We reasoned that the potential beneficial application of tropolone RNase H inhibition might be of therapeutic use if the toxic effects in mammalian cell were eliminated.  By selectively adding steric bulk to add new drug-enzyme contacts for the RNase H active site, a number of novel compounds, that have initially demonstrated reduced cytotoxicity, have been produced.  Importantly, these novel compounds appear to retain antiviral activity essential for use as therapeutics.

Potential Commercial Applications
  • As an HIV-1 therapeutic
Competitive Advantages
  • Potentially reduced toxicity
  • Availability of x-ray crystallographic information to guide analog design
Development Stage
Publications

Chung S, et al. Synthesis, activity and structural analysis of novel alpha-hydroxytropolone inhibitors of human immunodeficiency virus reverse transcriptase-associated ribonuclease H. [PMID 21568335]

Patent Status
  • U.S. Patent Issued: U.S. Patent Number , Filed 08 Nov 2013, Issued 31 Mar 2015
  • Foreign Issued: Foreign Filed - Patent Number
Therapeutic Area
Updated
Friday, April 20, 2018