Brain-penetrating 2-aminobenzimidazole H1-antihistamines for the treatment of insomnia

Exploration of a benzimidazole aminopiperidine core led to potent, selective and brain-penetrating H1-antihistamines. Efficacy in an EEG/EMG model was demonstrated. Further SAR focused on attenuation of a hERG liability, yielding compound 4i with an improved in vitro profile.