Syntheses and SAR studies of 4-(heteroarylpiperdin-1-yl-methyl)-pyrrolidin-1-yl-acetic acid antagonists of the human CCR5 chemokine receptor

K Shankaran; Karla L Donnelly; Shrenik K Shah; Ravindra N Guthikonda; Malcolm MacCoss; Sander G Mills; Sandra L Gould; Lorraine Malkowitz; Salvatore J Siciliano; Martin S Springer; Anthony Carella; Gwen Carver; Daria Hazuda; Karen Holmes; Joseph Kessler; Janet Lineberger; Michael D Miller; Emilio A Emini; William A Schleif

doi:10.1016/j.bmcl.2004.04.078

Syntheses and SAR studies of 4-(heteroarylpiperdin-1-yl-methyl)-pyrrolidin-1-yl-acetic acid antagonists of the human CCR5 chemokine receptor

Bioorg Med Chem Lett. 2004 Jul 5;14(13):3419-24. doi: 10.1016/j.bmcl.2004.04.078.

Affiliation

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

PMID: 15177445
DOI: 10.1016/j.bmcl.2004.04.078

Abstract

Efforts toward the exploration of the title compounds as CCR5 antagonists are disclosed. The basis for such work stems from the fact that cellular proliferation of HIV-1 requires the cooperative assistance of both CCR5 and CD4 receptors. The synthesis and SAR of pyrrolidineacetic acid derivatives as CCR5 antagonists displaying potent binding and antiviral properties in a HeLa cell-based HIV-1 infectivity assay are discussed.

MeSH terms

Acetates / chemistry
Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / pharmacology
Binding Sites
CCR5 Receptor Antagonists*
Cell Division / drug effects
HIV-1 / drug effects*
HeLa Cells
Humans
Piperidines / chemical synthesis
Piperidines / pharmacology
Pyrrolidines / chemical synthesis*
Pyrrolidines / chemistry
Structure-Activity Relationship

Substances

Acetates
Anti-HIV Agents
CCR5 Receptor Antagonists
Piperidines
Pyrrolidines