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

Abstract

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.

NMR-based investigations of acyl-functionalized piperazines concerning their conformational behavior in solution

“…The different energy barriers of both effects resulted in two different coalescence points. To further investigate the conformational behavior of the piperazines and to determine these energies, temperaturedependent NMR experiments 39 were performed for all derivatives in CDCl 3 and in DMSO-d 6 . Results are presented in Tables 2 and 3.…”

“…1 The piperazine scaffold has been integrated as a privileged structure and is frequently found in bioactive and pharmacologically relevant compounds across a number of different therapeutic areas. A wide variety of N-functionalized piperazines serve as skeletons in pesticides, pharmaceuticals [2][3][4] such as analgesics 5 and other drugs, 6,7 scaffolds in medicinal chemistry, [8][9][10] intermediates in organic reactions, 11,12 ligands for complexation purposes, [13][14][15] for peptide syntheses and modications 16,17 as well as building blocks in material sciences e.g. for polymerizations.…”

Sulfonylpiperazines based on a flavone as antioxidant and cytotoxic agents

“…In a light of aformentioned facts, we have designed chrysin‐based piperazine molecules, which includes the presence of one OH group in chyrsin core as well as substituting another OH group by desired active pharmacophores and these analogues appeared to have significant antioxidant and anticancer effects. Moreover, organic and inorganic precursors holding sulfone entity were found to have promising potential as biological active agents, whereas piperazine analgoues have been proposed to be a key factor enhancing biological effects of the bearing molecules. Most important, the piperazine‐based anticancer agents include abemaciclib, bosutinib, brigatinib, dexrazoxane, dosatinib, imatinib, leucovorin, olaparib, palbociclib, ponatinib, rociletinib, venetoclax, and trabectidin, and so forth .…”

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

“…Piperazine is an important structural core found in many biologically active natural products [1]. Piperazines are also useful intermediates in the synthesis of a variety of drug molecules having important biological activities such as anticancer [2–3], antifungal [4], amoebiasis, trypanosomiasis, bilharziasis [5–6], and schistosomiasis [7–8].…”