Synthesis and pharmacological evaluation of sulfone substituted HIV protease inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 7; no. 4; pp. 399 - 402
• Main Authors: Schwartz, Theresa M., Bundy, Gordon L., Strohbach, Joseph W., Thaisrivongs, Suvit, Johnson, Paul D., Skulnick, Harvey I., Tomich, Paul K., Lynn, Janet C., Chong, Kong Teck, Hinshaw, Roger R., Raub, Thomas J., Padbury, Guy E., Toth, Lisa N.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 18.02.1997; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Medical sciences; Pharmacology. Drug treatments; Cyclopropane derivatives; Cell permeability; Sulfone; HIV-1 virus; Enzyme; Enol; Pyran derivatives; Retroviridae; Enzyme inhibitor; Lactone; Oxygen heterocycle; In vitro; Virus; Peptidases; Structure activity relation; Bicyclic compound; Hydrolases; Lentivirinae; Antiviral; Human immunodeficiency virus; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(97)00031-0

The sulfonamide substituted pyranones ( 1) have recently been shown to be potent HIV protease inhibitors. We prepared a series of sulfone substituted analogs and compared their biological activities to those of the corresponding sulfonamide analogs. It was determined that although these compounds maintained activity as enzyme inhibitors, they showed somewhat diminished antiviral activity even though they may possess increased membrane permeability. The sulonamide substitued pyranones ( 1) have recently been shown to be potent HIV protease inhibitors. We prepared a series of sulfone substituted analogs and compared their biological activities to those of the corresponding sulfonamide analogs. It was determined that although these compounds maintained activity as enzyme inhibitors, they showed somewhat diminished antiviral activity even though they may possess increased membrane permeability.