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

K Shankaran; Karla L Donnelly; Shrenik K Shah; Charles G Caldwell; Ping Chen; Paul E Finke; Bryan Oates; Malcolm MacCoss; Sander G Mills; Julie A DeMartino; Sandra L Gould; Lorraine Malkowitz; Salvatore J Siciliano; Martin S Springer; Gloria Kwei; Anthony Carella; Gwen Carver; Renee Danzeisen; Daria Hazuda; Karen Holmes; Joseph Kessler; Janet Lineberger; Michael D Miller; Emilio A Emini; William A Schleif

doi:10.1016/j.bmcl.2004.03.112

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

Bioorg Med Chem Lett. 2004 Jul 5;14(13):3589-93. doi: 10.1016/j.bmcl.2004.03.112.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. kothandaraman_shankaran@merck.com

PMID: 15177481
DOI: 10.1016/j.bmcl.2004.03.112

Abstract

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.

MeSH terms

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

Substances

Anti-HIV Agents
CCR5 Receptor Antagonists
CD4 Antigens
Piperidines
Receptors, CCR5
Sulfones
piperidine