Discovery of N-benzyl-N'-(4-pipyridinyl)urea CCR5 antagonists as anti-HIV-1 agents (I): optimization of the amine portion

Maosheng Duan; Jennifer Peckham; Mark Edelstein; Robert Ferris; Wieslaw M Kazmierski; Andrew Spaltenstein; Pat Wheelan; Zhiping Xiong

doi:10.1016/j.bmcl.2010.10.033

Discovery of N-benzyl-N'-(4-pipyridinyl)urea CCR5 antagonists as anti-HIV-1 agents (I): optimization of the amine portion

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7397-400. doi: 10.1016/j.bmcl.2010.10.033. Epub 2010 Oct 12.

Authors

Maosheng Duan¹, Jennifer Peckham, Mark Edelstein, Robert Ferris, Wieslaw M Kazmierski, Andrew Spaltenstein, Pat Wheelan, Zhiping Xiong

Affiliation

¹ Infectious Diseases Center for Excellence in Drug Discovery, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. maosheng.a.duan@gsk.com

PMID: 21035337
DOI: 10.1016/j.bmcl.2010.10.033

Abstract

Several series of carbamate, urea and carboxamide-based CCR5 antagonists have been discovered via optimizations at the amine portion of lead compound 2. All compounds were evaluated for their antiviral activities. Lead urea 29 showed good pharmacokinetic properties, justifying further development of this series.

MeSH terms

Amines / chemistry*
Animals
Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / chemistry*
Anti-HIV Agents / pharmacokinetics
CCR5 Receptor Antagonists*
Cell Line, Tumor
Drug Evaluation, Preclinical
HIV-1 / drug effects*
Humans
Phenylurea Compounds / chemical synthesis
Phenylurea Compounds / chemistry*
Phenylurea Compounds / pharmacokinetics
Rats
Rats, Sprague-Dawley
Receptors, CCR5 / metabolism
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry*
Sulfonamides / pharmacokinetics
Urea / analogs & derivatives*
Urea / chemical synthesis
Urea / pharmacokinetics
Virus Replication / drug effects

Substances

Amines
Anti-HIV Agents
CCR5 Receptor Antagonists
Phenylurea Compounds
Receptors, CCR5
Sulfonamides
Urea