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Updated: Jun 6, 2025
11:45
Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
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"Angular" Spirocyclic Azetidines: Synthesis, Characterization, and Evaluation in Drug Discovery
Alexander A Kirichok1,2, Hennadii Tkachuk1, Kostiantyn Levchenko1,3
1Enamine Ltd, Winston Churchill st. 78, 02094, Kyiv, Ukraine.
Angewandte Chemie (International Ed. in English)
|December 2, 2024
Summary
Newly synthesized spirocyclic azetidines serve as effective bioisosteres for common heterocycles in drug discovery. These novel compounds yield patent-free analogs of existing drugs with maintained activity and properties.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Drug Discovery
Background:
- Spirocyclic azetidines are under-explored heterocyclic scaffolds.
- Common saturated six-membered heterocycles are frequently used in drug structures.
- Bioisosterism is a key strategy for drug optimization.
Purpose of the Study:
- To synthesize and characterize novel angular spirocyclic azetidines.
- To evaluate the potential of these azetidines as bioisosteres for six-membered heterocycles.
- To incorporate azetidines into known drug structures to create new analogs.
Main Methods:
- Synthesis of angular spirocyclic azetidines.
- Characterization of synthesized compounds.
- Incorporation of azetidines into Sonidegib and Danofloxacine scaffolds.
- Evaluation of physicochemical properties and biological activity of analogs.
Main Results:
- Successful synthesis and characterization of novel spirocyclic azetidines.
- Demonstrated bioisosteric replacement of morpholine and piperazine moieties.
- Generated patent-free analogs of Sonidegib and Danofloxacine.
- Analogs retained similar physicochemical properties and high biological activity.
Conclusions:
- Angular spirocyclic azetidines are viable and valuable bioisosteres.
- These scaffolds offer a route to novel, patent-free drug analogs.
- The findings support the utility of spirocyclic azetidines in drug discovery programs.
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