Syntheses and biological evaluation of 5-(piperidin-1-yl)-3-phenyl-pentylsulfones as CCR5 antagonists

• Published in: Bioorganic & medicinal chemistry letters Vol. 14; no. 13; pp. 3589 - 3593
• Main Authors: Shankaran, K., Donnelly, Karla L., Shah, Shrenik K., Caldwell, Charles G., Chen, Ping, Finke, Paul E., Oates, Bryan, MacCoss, Malcolm, Mills, Sander G., DeMartino, Julie A., Gould, Sandra L., Malkowitz, Lorraine, Siciliano, Salvatore J., Springer, Martin S., Kwei, Gloria, Carella, Anthony, Carver, Gwen, Danzeisen, Renee, Hazuda, Daria, Holmes, Karen, Kessler, Joseph, Lineberger, Janet, Miller, Michael D., Emini, Emilio A., Schleif, William A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 05-07-2004
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - pharmacology; Binding Sites; CCR5 Receptor Antagonists; CD4 Antigens - metabolism; Cell Line; Drug Design; Humans; Inhibitory Concentration 50; Piperidines - chemistry; Receptors, CCR5 - metabolism; Stereoisomerism; Structure-Activity Relationship; Sulfones - chemical synthesis; Sulfones - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.03.112

Ongoing efforts from these laboratories have resulted in the identification of 5-(piperidin-1-yl)-3-phenylpentylsulfones as a potent CCR5 antagonists. The syntheses and biological activities such as analogs are described.
Cellular proliferation of HIV-1 requires the cooperative assistance of both the CCR5 and CD4 receptors. Our medicinal chemistry efforts in this area have resulted in the identification of
N-alkyl piperidine sulfones as CCR5 antagonists. These compounds display potent binding and show antiviral properties in HIV-1 spread cell-based assays.