Piperazine derivatives for therapeutic use: a patent review (2010-present)

ABSTRACT

Introduction: Piperazine, a six membered nitrogen containing heterocycle, is of great significance to the rational design of drugs. This moiety can be found in a plethora of well-known drugs with various therapeutic uses, such as antipsychotic, antihistamine, antianginal, antidepressant, anticancer, antiviral, cardio protectors, anti-inflammatory, and imaging agents. Slight modification to the substitution pattern on the piperazine nucleus facilitates a recognizable difference in the medicinal potential of the resultant molecules.

Areas covered: Scifinder was the main source used to search for patents containing piperazine compounds with therapeutic uses. The article describes a variety of molecular designs bearing piperazine entity furnishing CNS agents, anticancer, cardio-protective agents, antiviral, anti-tuberculosis, anti-inflammatory, antidiabetic, and antihistamine profiles, as well as agents relieving pain and useful in imaging applications.

Expert opinion: The great interest gathered to explore piperazine based molecules in relatively few years reflects the broad potential of the entity. Earlier, this scaffold was considered to express CNS activity only. However, a significant increase in research covering studies of several different activities of piperazine ring suggest a successful emergence of the pharmacophore. Certain patents outlined in the present article recommend that piperazines can be a flexible building block to discover drug-like elements and modification of substituents present on the piperazine ring may have a significant impact on the pharmacokinetic and pharmacodynamics factors of the resulting molecules. This article aims to provide insights to piperazine based molecular fragments that would assist drug discoverers to rationally design molecules for various diseases. We anticipate, and highly recommend, further therapeutic investigations on this motif.

KEYWORDS:

• Anticancer
• antihistamine
• anti-inflammatory
• anti-tuberculosis
• antiviral
• cardio-protective
• CNS disorder
• imaging agents
• piperazine
• pain

Article highlights

• Piperazine moieties are emerging as a primary scaffold to enhance the drug-like properties of the molecules in the rational drug design process

• Piperazine skeleton have been found in a variety of marketed drugs of the various therapeutic categories.

• Piperazines can be a good replacement to other nucleophiles in order to influence the overall pharmacological profiles of the parent molecules positively.

• Substituent present on the piperazine ring system may be the factor responsible for the variable drug-like action of the molecule.

• Molecules possessing piperazine entities can be useful to target multiple pharmacological activities.

This box summarizes key points contained in the article.

Declaration of interest

This article is supported by Dongguk University, Seoul, Republic of Korea, research funds 2016-2017. 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 apart from those disclosed.