Synthesis, biological evaluation, and molecular modeling of ORM-10921 and its analogs as α -adrenoceptor antagonists.

The α -adrenoceptor (α -AR) is regarded as one of the potential targets for antipsychotics. A few of structurally diverse α -AR antagonists have been reported, among which ORM-10921, containing one rigid tetracyclic framework with two neighboring chiral centers, has exhibited remarkable antipsychotic-like effects and pro-cognitive properties in different animal models. Yet the binding mode of ORM-10921 remains elusive.