Synthesis and evaluation of 2-phenyl-1,4-butanediamine-based CCR5 antagonists for the treatment of HIV-1

Matthew D Tallant; Maosheng Duan; George A Freeman; Robert G Ferris; Mark P Edelstein; Wieslaw M Kazmierski; Pat J Wheelan

doi:10.1016/j.bmcl.2011.01.030

Synthesis and evaluation of 2-phenyl-1,4-butanediamine-based CCR5 antagonists for the treatment of HIV-1

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1394-8. doi: 10.1016/j.bmcl.2011.01.030. Epub 2011 Jan 11.

Authors

Matthew D Tallant¹, Maosheng Duan, George A Freeman, Robert G Ferris, Mark P Edelstein, Wieslaw M Kazmierski, Pat J Wheelan

Affiliation

¹ Department of Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. [email protected]

PMID: 21292480
DOI: 10.1016/j.bmcl.2011.01.030

Abstract

We describe the synthesis and potency of a novel series of N-substituted 2-phenyl- and 2-methyl-2-phenyl-1,4-diaminobutane- based CCR5 antagonists. Compounds 7a and 12f were found to be potent in anti-HIV assays and bioavailable in the low-dose rat PK model.

MeSH terms

Animals
Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / chemistry
Anti-HIV Agents / pharmacokinetics
Anti-HIV Agents / pharmacology
CCR5 Receptor Antagonists*
Cell Line
Disease Models, Animal
HIV Infections / drug therapy
HIV-1 / drug effects
Inhibitory Concentration 50
Putrescine / chemistry*
Rats
Rats, Sprague-Dawley

Substances

Anti-HIV Agents
CCR5 Receptor Antagonists
Putrescine