Discovery of N-benzyl-N'-(4-pipyridinyl)urea CCR5 antagonists as anti-HIV-1 agents (II): modification of the acyl portion

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

doi:10.1016/j.bmcl.2010.10.042

Discovery of N-benzyl-N'-(4-pipyridinyl)urea CCR5 antagonists as anti-HIV-1 agents (II): modification of the acyl portion

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7401-4. doi: 10.1016/j.bmcl.2010.10.042. Epub 2010 Oct 21.

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 Ttriangle Park, NC 27709, USA. [email protected]

PMID: 21055933
DOI: 10.1016/j.bmcl.2010.10.042

Abstract

Modification of the acyl moiety in the CCR5 lead molecule 2 led to identification of several new classes of CCR5 antagonists. Antiviral activity and pharmacokinetic properties of the synthesized compounds were evaluated. Structure-activity relationship (SAR) derived from these studies further guided the optimization efforts, ultimately leading to the discovery of 36 with an acceptable drug-like profile.

MeSH terms

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

Substances

Anti-HIV Agents
CCR5 Receptor Antagonists
Pyridines
Receptors, CCR5
Urea
pyridine