[2-(4-Phenyl-4-piperidinyl)ethyl]amine based CCR5 antagonists: derivatizations at the N-terminal of the piperidine ring

Maosheng Duan; Christopher Aquino; Robert Ferris; Wieslaw M Kazmierski; Terry Kenakin; Cecilia Koble; Pat Wheelan; Chris Watson; Michael Youngman

doi:10.1016/j.bmcl.2009.02.014

[2-(4-Phenyl-4-piperidinyl)ethyl]amine based CCR5 antagonists: derivatizations at the N-terminal of the piperidine ring

Bioorg Med Chem Lett. 2009 Mar 15;19(6):1610-3. doi: 10.1016/j.bmcl.2009.02.014. Epub 2009 Feb 10.

Authors

Maosheng Duan¹, Christopher Aquino, Robert Ferris, Wieslaw M Kazmierski, Terry Kenakin, Cecilia Koble, Pat Wheelan, Chris Watson, Michael Youngman

Affiliation

¹ Infectious Diseases Center for Excellence in Drug Discovery, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA.

PMID: 19233649
DOI: 10.1016/j.bmcl.2009.02.014

Abstract

Several series of CCR5 antagonists have been discovered by derivatization at the N-terminal of the piperidine ring of the core template 2. Some derivatives exhibited potent inhibition against HIV-1infection. The pharmacokinetic properties of the lead compounds 11a, 14a, 15b, and 16b have been evaluated in vivo.

MeSH terms

Animals
Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / pharmacology
CCR5 Receptor Antagonists*
CHO Cells
Chemistry, Pharmaceutical / methods
Cricetinae
Cricetulus
Drug Design
HIV Infections / drug therapy*
HIV-1 / metabolism
Inhibitory Concentration 50
Molecular Conformation
Piperidines / chemical synthesis*
Piperidines / pharmacology
Protein Structure, Tertiary
Rats
Receptors, CCR5 / chemistry

Substances

Anti-HIV Agents
CCR5 Receptor Antagonists
Piperidines
Receptors, CCR5
piperidine