The piperazine scaffold for novel drug discovery efforts: the evidence to date

ABSTRACT

Introduction

Piperazine is a structural element present in drugs belonging to various chemical classes and used for numerous different therapeutic applications; it has been considered a privileged scaffold for drug design.

Areas covered

The authors have searched examples of piperazine-containing compounds among drugs recently approved by the FDA and in some research fields (nicotinic receptor modulators, compounds acting against cancer, and bacterial multidrug resistance), looking in particular to the design behind the insertion of this moiety.

Expert opinion

Piperazine is widely used due to its peculiar characteristics, such as solubility, basicity, chemical reactivity, and conformational properties. This moiety has represented an important tool to modulate pharmacokinetic and pharmacodynamic properties of drugs.

KEYWORDS:

• Antibacterial drugs
• multidrug resistance
• nicotinic acetylcholine receptor ligands
• physicochemical properties
• piperazine
• rigid analogues

Article highlights

• Piperazine is a structural element present in drugs belonging to various chemical classes.

• The physicochemical properties of this water-soluble heterocycle can be effectively modulated by substituents on N and C atoms.

• A piperazine ring has been inserted in many drugs to improve pharmacokinetic properties.

• The chemical reactivity of piperazine facilitates its use to link different pharmacophores in the same molecule or as scaffold for the group important for the interaction with the target macromolecule.

• The conformational flexibility of piperazine can be reduced by inserting it into more complex polycyclic structures.

• Piperazine represents a versatile scaffold around which new drugs can be designed.

This box summarizes key points contained in the article.

Acknowledgments

We wish to thank the University of Florence for providing access to literature facilities.

Declaration of Interest

The authors have no 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.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.