Novel benzothiophene H1-antihistamines for the treatment of insomnia

Structure–activity relationships around the lead H1-antihistamine 2, a potential agent for the treatment of insomnia, led to the identification of several potential backups with differences in projected pharmacokinetic profiles. While human PK of 16d indicated a suitable half-life, the compound was not moved into development due to significant variability in pharmacokinetic profile. From preclinical studies, compound 28b may represent a more suitable backup.