Synthesis and evaluation of CCR5 antagonists containing modified 4-piperidinyl-2-phenyl-1-(phenylsulfonylamino)-butane

Shrenik K Shah; Natalie Chen; Ravindra N Guthikonda; Sander G Mills; Lorraine Malkowitz; Martin S Springer; Sandra L Gould; Julie A Demartino; Anthony Carella; Gwen Carver; Karen Holmes; William A Schleif; Renee Danzeisen; Daria Hazuda; Joseph Kessler; Janet Lineberger; Michael Miller; Emilio A Emini; Malcolm MacCoss

doi:10.1016/j.bmcl.2004.12.044

Synthesis and evaluation of CCR5 antagonists containing modified 4-piperidinyl-2-phenyl-1-(phenylsulfonylamino)-butane

Bioorg Med Chem Lett. 2005 Feb 15;15(4):977-82. doi: 10.1016/j.bmcl.2004.12.044.

Affiliation

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

PMID: 15686896
DOI: 10.1016/j.bmcl.2004.12.044

Abstract

Synthesis of analogs containing more rigid bicyclic piperidine replacements for the 4-benzyloxycarbonyl-(ethyl)amino-piperidine moiety of the CCR5 antagonist structure, 1, is described. Although similar binding affinity to the lead was achieved with some analogs they were overall less potent anti-HIV agents suggesting that other features besides CCR5 binding are required for good anti-viral activity.

MeSH terms

Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / pharmacology
Butanes / chemical synthesis
Butanes / pharmacology
CCR5 Receptor Antagonists*
Dose-Response Relationship, Drug
Inhibitory Concentration 50
Piperidines / chemical synthesis
Piperidines / pharmacology
Structure-Activity Relationship
Sulfones / chemical synthesis*
Sulfones / pharmacology
Viruses / drug effects

Substances

Anti-HIV Agents
Butanes
CCR5 Receptor Antagonists
Piperidines
Sulfones