Novel imidazobenzazepine derivatives as dual H1/5-HT2A antagonists for the treatment of sleep disorders.

Abstract A novel imidazobenzazepine template ( 5a ) with potent dual H 1 /5-HT 2A antagonist activity was identified. Application of a zwitterionic approach to this poorly selective and poorly developable starting point successfully delivered a class of high quality leads, 3-[4-(3-R 1 -2-R-5H-imidazo[1,2- b ][2]benzazepin-11-yl)-1-piperazinyl]-2,2-dimethylpropanoic acids (e.g., 9 , 19 , 20 , and 21 ), characterized by potent and balanced H 1 /5-HT 2A receptor antagonist activities and good developability profiles.