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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Diarylacetylene piperidinyl amides as novel anxiolytics
Cheryl P Kordik1, Chi Luo, Maryann Gutherman
1Drug Discovery Division, Johnson & Johnson Pharmaceutical Research and Development LLC, Welsh and McKean Roads, Spring House, PA 19477, USA. ckordik@prdus.jnj.com
Bioorganic & Medicinal Chemistry Letters
|April 4, 2006
Summary
New piperidine acetamide derivatives show promise for anxiety treatment, demonstrating good oral activity in animal models. These compounds also exhibit modest affinity for neurokinin receptors involved in mood regulation.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Anxiety disorders represent a significant global health burden.
- Neurokinin receptors (NK-1 and NK-2) are implicated in mood and emotional regulation.
- Developing novel anxiolytic agents targeting these pathways is a key research area.
Purpose of the Study:
- To evaluate the anxiolytic potential of N-Phenyl-2-[1-[3-(2-pyridinylethynyl)benzoyl]-4-piperidine]acetamide (9) and related compounds.
- To investigate the in vivo efficacy of these derivatives in a recognized animal model of anxiety.
- To explore the receptor binding profile, specifically for neurokinin receptors.
Main Methods:
- Utilized the elevated plus maze, a standard animal model for assessing anxiety-like behavior.
- Administered piperidine acetamide derivatives orally to evaluate their efficacy.
- Performed receptor binding assays to determine affinity for neurokinin NK-1 and NK-2 receptors.
Main Results:
- Compound (9) and related derivatives exhibited significant oral activity in the elevated plus maze.
- These findings suggest a predictive value for clinical efficacy in anxiety treatment.
- Modest binding affinity was observed for both neurokinin NK-1 and NK-2 receptors.
Conclusions:
- Piperidine acetamide derivatives, including compound (9), possess promising anxiolytic properties.
- The observed activity in the elevated plus maze supports their potential as therapeutic agents for anxiety.
- The modest affinity for neurokinin receptors warrants further investigation into their precise role in the observed effects.
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