Spirocyclic Scaffolds in Medicinal Chemistry
Kerstin Hiesinger1, Dmitry Dar'in2, Ewgenij Proschak1
1Institute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue Straße 9, D-60348 Frankfurt am Main, Germany.
Journal of Medicinal Chemistry
|December 31, 2020
Summary
Spirocyclic scaffolds are increasingly used in drug discovery due to their unique properties. This perspective reviews synthetic methods and medicinal chemistry applications of these important molecular architectures.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Drug Discovery
Background:
- Spirocyclic scaffolds are prevalent in approved drugs and drug candidates.
- There is a growing demand for non-planar bioactive molecules.
- Synthetic methodologies for spirocycles are actively developing.
Purpose of the Study:
- To summarize diverse synthetic routes for spirocyclic systems.
- To discuss the impact of spirocycles on drug potency, selectivity, and stereochemistry.
- To examine property and ADME changes in spirocyclic compounds.
Main Methods:
- Literature review of synthetic methodologies.
- Analysis of structure-activity relationships.
- Comparison of spirocyclic and non-spirocyclic compounds' properties and ADME profiles.
Main Results:
- Diverse synthetic strategies for spirocycles are available.
- Spirocycles can positively influence potency, selectivity, and physicochemical properties.
- Stereochemistry plays a crucial role in the biological activity of spirocyclic compounds.
Conclusions:
- Spirocyclic scaffolds offer significant advantages in medicinal chemistry.
- Their unique three-dimensional structures can enhance drug efficacy and pharmacokinetic profiles.
- Continued exploration of spirocycles is vital for future drug development.
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
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