A Decade of Piperazine-Based Small Molecules Approved by U.S. FDA: Exploring the Medicinal Chemistry Impact of this Versatile Pharmacophore

Kapil Kumar Goel; Peeush Singhal; Arockia Babu Marianesan; Sarvesh Kumar Pandey; Roshan Kumar; Thakur Gurjeet Singh; Yogita Tyagi; Shilpa Gaidhane; Mahendra Pratap Singh; Ashish Ranjan Dwivedi

doi:10.1055/a-2508-9961

Synlett, Table of Contents

Synlett 2025; 36(17): 2802-2818
DOI: 10.1055/a-2508-9961

perspectives

Small Molecules in Medicinal Chemistry

A Decade of Piperazine-Based Small Molecules Approved by U.S. FDA: Exploring the Medicinal Chemistry Impact of this Versatile Pharmacophore

Authors

Kapil Kumar Goel

^aDepartment of Pharmaceutical Sciences, Gurukul Kangri (Deemed to be University), Haridwar-249404 Uttarakhand, India
Peeush Singhal

^aDepartment of Pharmaceutical Sciences, Gurukul Kangri (Deemed to be University), Haridwar-249404 Uttarakhand, India
Arockia Babu Marianesan

^bInstitute of Pharmaceutical Research, GLA University, Mathura, 17, Km Stone, National Highway #2, Delhi-Mathura Road, India
Sarvesh Kumar Pandey

^cDepartment of Chemistry, D. D. U. Gorakhpur University, Gorakhpur, India
Roshan Kumar

^dDepartment of Microbiology, Graphic Era (Deemed to be University), Clement Town Dehradun-248002, India
Thakur Gurjeet Singh

^eCentre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
Yogita Tyagi

^fUttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Premanagar, Dehradun 248007, Uttarakhand, India
Shilpa Gaidhane

^gOne Health Centre, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education, Wardha, India
Mahendra Pratap Singh

^hCenter for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
Ashish Ranjan Dwivedi ∗

ⁱGITAM School of Pharmacy, GITAM (Deemed to be) University, Hyderabad, India

Abstract

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Abstract

Heterocyclic scaffolds, particularly azaheterocycles, are part of numerous clinically relevant drugs. We have explored U.S. FDA approved small-molecule drugs (2012–2023) containing piperazine as a core ring system. The analysis revealed that 36 drugs approved in the last decade possess piperazine ring systems, with 15 drugs falling within the anticancer category. The CYP3A4 was found to be the primary enzyme responsible for the metabolism of these drugs, and most of them undergo fecal excretion. Considering stereochemical aspects, nine piperazine-containing drugs were found to be with chiral centers. The perspective is a concerted effort to cover not only the drugs bearing piperazine rings containing drugs but also provides a thorough discussion and commentaries on their pharmacokinetics and pharmacodynamics aspects. This enriches the article’s medicinal chemistry aspect and makes it a good read for the medicinal and allied science community.

1 Introduction

2 Insights into the Chemistry of Piperazine and Comparative Analysis of Molecular and Chemical Spacing Descriptors

3 Synthetic Strategies to Develop Piperazine Derivative

4 Comparative Analysis of the Pharmacological Class of the Approved Drugs Possessing a Piperazine Ring System

5 Delving Deeper into the Approved Drugs Bearing the Piperazine-Based Core Systems

6 Analysis

7 Conclusion

Key words

heterocycles - piperazine - drug discovery - US FDA approved - chemical space - molecular descriptors - chemical analysis - metabolism

Full Text

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