Recent developments concerning the application of the Mannich reaction for drug design

ABSTRACT

Introduction: The versatile multicomponent Mannich reaction occupies a salient position in organic chemistry and drug design. Sound knowledge of its scope and variations and of the biological activities of Mannich bases is crucial for the development and improvement of drugs for various diseases.

Areas covered: The following article provides an overview of the latest developments in the field of drugs based on the Mannich reaction. Web-based literature searching tools such as PubMed and SciFinder were applied to obtain useful articles. In addition, pertinent literature that was recently published by the authors is discussed in this manuscript. The chemical structures of bioactive Mannich bases are also given.

Expert opinion: The Mannich reaction represents a feasible and cost-effective procedure with great potential for drug development. Several newly discovered Mannich bases exhibit sound activities against various human diseases as well as favorable pharmacokinetics. Thus, scientific research about Mannich bases is prospering and appears very attractive both for chemists and for clinicians.

KEYWORDS:

• Aminoalkylation
• bioavailability
• drug design
• Mannich bases
• Mannich reaction
• multicomponent reaction

Article highlights

• The Mannich reaction is a cost-effective, robust three-component reaction with many applications in chemistry and drug design.

• The Mannich reaction is applicable to the aminoalkylation of phenols, electron-rich heterocycles, and enolizable ketones.

• Aminoalkylation of drugs can significantly improve their activity, solubility and bioavailability.

• Quite a few new Mannich bases are auspicious drug candidates for diseases such as cancer, infectious diseases, epilepsy, Alzheimer’s disease, inflammation and pain.

• Several new Mannich bases revealed promising activity in animal models of the targeted disease with potential to be developed to clinically applicable drugs in the near future.

This box summarizes key points contained in the article.

Declaration of interest

B Biersack is grateful to the Maharashtra Cosmopolitan Education Society (Mr. P.A. Inamdar and Mrs. Abeda Inamdar) and Dr. E.M. Khan, Principal of the Abeda Inamdar Senior College, Pune, for the provision of a scholarship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

R Schobert thanks the Deutsche Forschungsgemeinschaft (DFG) for a grant [Scho 402/12-1].