2. Academic Validation
  3. Two-carbon-elongated HIV-1 protease inhibitors with a tertiary-alcohol-containing transition-state mimic

Two-carbon-elongated HIV-1 protease inhibitors with a tertiary-alcohol-containing transition-state mimic

  • J Med Chem. 2008 Feb 28;51(4):1053-7. doi: 10.1021/jm070680h.
Xiongyu Wu 1,  Per Ohrngren,  Jenny K Ekegren,  Johan Unge,  Torsten Unge,  Hans Wallberg,  Bertil Samuelsson,  Anders Hallberg,  Mats Larhed
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
PMID: 18215014 DOI: 10.1021/jm070680h
Abstract

A new generation of HIV-1 Protease Inhibitors encompassing a tertiary-alcohol-based transition-state mimic has been developed. By elongation of the core structure of recently reported inhibitors with two carbon atoms and by varying the P1' group of the compounds, efficient inhibitors were obtained with Ki down to 2.3 nM and EC50 down to 0.17 microM. Two inhibitor-enzyme X-ray structures are reported.

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