Discovery of a novel series of cyclic urea as potent CCR5 antagonists

Maosheng Duan; Wieslaw M Kazmierski; Matt Tallant; Jung Ho Jun; Mark Edelstein; Rob Ferris; Dan Todd; Pat Wheelan; Zhiping Xiong

doi:10.1016/j.bmcl.2011.08.096

Discovery of a novel series of cyclic urea as potent CCR5 antagonists

Bioorg Med Chem Lett. 2011 Nov 1;21(21):6381-5. doi: 10.1016/j.bmcl.2011.08.096. Epub 2011 Aug 28.

Authors

Maosheng Duan¹, Wieslaw M Kazmierski, Matt Tallant, Jung Ho Jun, Mark Edelstein, Rob Ferris, Dan Todd, Pat Wheelan, Zhiping Xiong

Affiliation

¹ Infectious Disease Medicine Discovery and Development, GlaxoSmithKline Five Moore Drive, Research Triangle Park, NC 27706, USA.

PMID: 21930378
DOI: 10.1016/j.bmcl.2011.08.096

Abstract

A novel series of cyclic urea-based CCR5 antagonists was designed aiming to resolve instability issue in the fasted simulated intestinal fluid (FSIF) associated with the acyclic urea moiety in 1. This class of CCR5 compounds demonstrated high antiviral activities against HIV-1 infection in both HOS and PBL assays. Further evaluation of these compounds indicated that 16-R not only substantially enhanced its stability, but also exhibited excellent pharmacokinetics properties.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemistry
Anti-HIV Agents / pharmacology*
CCR5 Receptor Antagonists*
Drug Discovery*
HIV-1 / drug effects
Urea / chemistry*
Urea / pharmacology*

Substances

Anti-HIV Agents
CCR5 Receptor Antagonists
Urea