title: Discovery of a novel series of cyclic urea as potent CCR5 antagonists.
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.
authors.affiliation: Infectious Disease Medicine Discovery and Development, GlaxoSmithKline Five Moore Drive, Research Triangle Park, NC 27706, USA.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Duan
authors.forename: Wieslaw M
authors.initials: WM
authors.lastname: Kazmierski
authors.forename: Matt
authors.initials: M
authors.lastname: Tallant
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Jun
authors.forename: Mark
authors.initials: M
authors.lastname: Edelstein
authors.forename: Rob
authors.initials: R
authors.lastname: Ferris
authors.forename: Dan
authors.initials: D
authors.lastname: Todd
authors.forename: Pat
authors.initials: P
authors.lastname: Wheelan
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Xiong
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D055808:Drug Discovery; D015497:HIV-1 / Q000187:drug effects; D014508:Urea / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D014508:Urea