title: Anti-HIV-1 entry optimization of novel imidazopiperidine-tropane CCR5 antagonists.
abstract: A novel series of imidazopiperidine-tropane CCR5 antagonists is described. The series was optimized for anti-HIV-1 potency using a set of phenotypic viral entry assays. This strategy resulted in the identification of several very potent (IC(50)<10nM) inhibitors of HIV-1 entry. One compound (40) was further profiled and was found to have attractive selectivity, pharmacokinetic, and antiviral properties.
authors.affiliation: Department of Medicinal Chemistry, Kémia, Inc., 5871 Oberlin Drive, San Diego, CA 92121, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Ernst
authors.forename: Russell
authors.initials: R
authors.lastname: Dahl
authors.forename: Christopher
authors.initials: C
authors.lastname: Lum
authors.forename: Lubomir
authors.initials: L
authors.lastname: Sebo
authors.forename: Jan
authors.initials: J
authors.lastname: Urban
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Miller
authors.forename: Jan
authors.initials: J
authors.lastname: Lundström
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D007093:Imidazoles; D010880:Piperidines; D014326:Tropanes