Details

Autor(en) / Beteiligte

• Thaisrivongs, Suvit
• Tomasselli, Alfredo G
• Moon, Joseph B
• Hui, John
• McQuade, Thomas J
• Turner, Steve R
• Strohbach, Joseph W
• Howe, W. Jeffrey
• Tarpley, W. Gary
• Heinrikson, Robert L

Titel

Inhibitors of the protease from human immunodeficiency virus: design and modeling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective antiviral activity

Ist Teil von

• Journal of medicinal chemistry, 1991-08, Vol.34 (8), p.2344-2356

Ort / Verlag

Washington, DC: American Chemical Society

Erscheinungsjahr

1991

Quelle

MEDLINE

Beschreibungen/Notizen

• The peptidomimetic template and the dihydroxyethylene isostere insert that were applied successfully to the design of renin inhibitors have been extended to the related protease from human immunodeficiency virus (HIV). The present report describes the structure-activity study leading to the identification of an inhibitor with a Ki of less than 1 nM for the HIV type-1 protease (compound II). This compound, containing a diol insert, is highly effective in blocking polyprotein processing in in vitro cell culture assays. Results obtained from kinetic analysis, studies of the stereochemistry of the insert, and modeling have led to insights as to the requisites involved in the active site-inhibitor interaction.