Anti-HIV-1 entry optimization of novel imidazopiperidine-tropane CCR5 antagonists

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 (IC50 < 10 nM) inhibitors of HIV-1 entry. One compound (40) was further profiled and was found to have attractive selectivity, pharmacokinetic, and antiviral properties.

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 (IC50 < 10 nM) inhibitors of HIV-1 entry. One compound (40) was further profiled and was found to have attractive selectivity, pharmacokinetic, and antiviral properties.Figure optionsDownload as PowerPoint slide