Synthesis, biological evaluation, and molecular modeling of ORM‐10921 and its analogs as α2C‐adrenoceptor antagonists

• DOI: 10.1002/ardp.202300125
• Publication Date: 2023-05-19T03:07:14Z
• Authors: Qiaoning Ma; Lingxuan Zhu; Zhe Zhang; Ying Xiong; Yan Li; Xinsheng Lei
• Keywords: Docking (animal); Molecular model

The α2C -adrenoceptor (α2C -AR) is regarded as one of the potential targets for antipsychotics. A few structurally diverse -AR antagonists have been reported, among which ORM-10921, containing rigid tetracyclic framework with two neighboring chiral centers, has exhibited remarkable antipsychotic-like effects and pro-cognitive properties in different animal models. Yet binding mode ORM-10921 remains elusive. In this study, all its four stereoisomers a set analogs were synthesized vitro evaluated their antagonist activities. molecular docking study hydration site analysis gave rational explanation biological results, might provide helpful insights into future optimization.