Affiliation:
1. School of Pharmacy Fudan University Shanghai China
Abstract
AbstractThe α2C‐adrenoceptor (α2C‐AR) is regarded as one of the potential targets for antipsychotics. A few of structurally diverse α2C‐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. In this study, all of its four stereoisomers and a set of its analogs were synthesized and in vitro evaluated for their α2C‐AR antagonist activities. The molecular docking study and hydration site analysis gave a rational explanation for the biological results, which might provide helpful insights into the binding mode and future optimization.
Funder
National Natural Science Foundation of China
Science and Technology Commission of Shanghai Municipality
Subject
Drug Discovery,Pharmaceutical Science