3BC4

Targeting the open-flap conformation of HIV-1 protease with pyrrolidine-based inhibitors

(2008) ChemMedChem 3: 1337-1344

• PubMed: 18720485 Search on PubMed
• DOI: https://doi.org/10.1002/cmdc.200800113
• Primary Citation of Related Structures:  
  3BC4


• PubMed Abstract: 
  

  HIV protease is a well-established drug target in antiviral chemotherapy. Immense research efforts have been made to discover effective inhibitors, thus making the enzyme one of the most studied and best characterized proteins. Although the protease exhibits high flexibility, all approved drugs target virtually the same protein conformation. The development of viral cross-resistance demands the generation of inhibitors with novel scaffolds and deviating modes of binding. Herein we report the design and the short, high-yielding stereoselective synthesis of a series of chiral, symmetric pyrrolidine-based inhibitors targeting the open-flap conformation of the protease. The obtained co-crystal structure with one derivative provides a valuable starting point for further inhibitor design.

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Organizational Affiliation: 

Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marbacher Weg 6, 35032 Marburg, Germany.