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![Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F59557.jpg&w=3840&q=50)
Technical Aspect of the Automated Synthesis and Real-Time Kinetic Evaluation of [11C]SNAP-7941
Published on: April 28, 2019
Synthesis, biological evaluation, and molecular modeling of ORM-10921 and its analogs as α2C -adrenoceptor
Qiaoning Ma1, Lingxuan Zhu1, Zhe Zhang1
1School of Pharmacy, Fudan University, Shanghai, China.
Abstract:
The 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.
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