Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomnia

Several indenes with high affinity for the H1 receptor and appropriate selectivity versus off-targets were assessed for metabolism profile and in vivo properties. Compound 10a displayed a diversified metabolism profile, showed equivalent efficacy in a rat EEG/EMG model to a previously identified clinical candidate, and a potentially superior pharmacokinetic profile as determined from a human microdose study.