HIV-1 Integrase Inhibitors for the Treatment of Retroviral Infections
Posted Jun 13 2010 5:00pm
Description of Invention: This technology describes the structure and activity of N-benzyl derivatives of 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-ones and 2,3-dihydro-6,7-dihydroxy-1H-isoindole-1,3(2H)-diones as new HIV-1 integrase inhibitors. HIV, as well as other retroviruses, requires three key viral enzymes for replication: Reverse transcriptase, protease and integrase (IN). A significant number of patients fail to respond to combination therapies consisting of reverse transcriptase and protease inhibitors, due to the development of viral resistance. IN functions by initial processing of viral cDNA in a cleavage step termed 3’-processing (3’-P). This is followed by insertion of the cleaved cDNA into the host genome in a reaction known as “strand transfer” (ST). Certain agents covered under the subject technology have been shown to exhibit selective inhibition of ST reactions relative to 3’-P reactions. These compounds inhibit purified IN in vitro and are also active against HIV-1 derived vectors in cell-based assay. These inhibitors may have a potential therapeutic value for retroviral infections, including AIDS, especially for patients exhibiting drug resistant to current therapy regimes.
Applications: The treatment and prevention for HIV infections.
WG Verschueren et al. Design and optimization of tricyclic phtalimide analogue as novel inhibitors of HIV-1 integrase. J Med Chem. 2005 Mar 24;48(6):1930-1940. [ PubMed abs ]
Licensing Status: Available for licensing.
Collaborative Research Opportunity: The National Cancer Institute's Laboratory of Medicinal Chemistry and Laboratory of Molecular Pharmacology are seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the HIV-1 integrase inhibitors described. Please contact John D. Hewes, Ph.D. at 301-435-3121 or firstname.lastname@example.org for more information.
Portfolios: Infectious Diseases Infectious Diseases - Therapeutics In-vitro Data