Piperazine derivatives with central pharmacological activity used as therapeutic tools

Abstract

Medicinal chemistry is a science applied to the search and discovery of new therapeutic agents for the treatment of various diseases. Therefore, promising structures have been identified; one of these structures is the piperazine moiety, a cyclic molecule containing two nitrogen atoms in positions 1 and 4 as well as four carbon atoms. Many piperazine derivatives have central pharmacological activity that mainly involves the activation of the monoamine pathway. Thus, piperazine derivatives have been the subject of research for many central therapeutic applications, including antipsychotic, antidepressant and anxiolytic applications. Benzylpiperazine is the prototype of piperazine derivatives; this substance is the main component of recreational drugs, partly due to its stimulant and euphoric effects. This paper describes some piperazine derivatives used therapeutically as antipsychotic (clozapine), antidepressant (vortioxetine) and anxiolytic (buspirone) drugs.

Anxiolytic‐like effects of the new arylpiperazine derivatives containing isonicotinic and picolinic nuclei: behavioral and biochemical studies

“…Included in this group are agomelatine (a 5‐HT 2C antagonist) and melatonin (an MT1 and MT2 agonist) . Also, most of third‐generation antipsychotics are blockers of these receptors . Moreover, it has been also shown that in the anxiolytic effects of 5‐HT 1A receptor ligands may indirectly involve the GABA A ‐BDZ receptor complex .…”

“…Herein, substituted phenyl is typically located in the aryl position, while the heterocyclic nucleus is an amide or imide . The piperazine moiety is one of these active structures with important heterocyclic nuclei and exhibits various pharmacological activities .…”

Crystal structures of the recreational drug N-(4-methoxyphenyl)piperazine (MeOPP) and three of its salts

“…The action of MeOPP on human physiology is similar to that of amphetamines, but it has a significantly lower potential for abuse (Nagai et al, 2007). In view of these observations, coupled with the broad range of biological activities exhibited by piperazine derivatives in general (Asif, 2015;Brito et al, 2019), we have recently initiated a programme of study centred on N-(4-methoxyphenyl)piperazine derivatives. Thus, we have recently reported the synthesis and structures of a range of salts derived from MeOPP (Kiran , as well as those of a range of neutral 1-aroyl-4-(4methoxyphenyl)piperazines (Kiran Kumar, Yathirajan, Sagar et al, 2019).…”

Six 1-aroyl-4-(4-methoxyphenyl)piperazines: similar molecular structures but different patterns of supramolecular assembly

“…Piperazines are found in a wide range of compounds which are active across a number of different therapeutic areas such as antibacterial, antidepressant, antifungal, antimalarial, antipsychotic, and antitumour activity (Brockunier et al, 2004;Bogatcheva et al, 2006), and a number of these areas have recently been reviewed (Elliott, 2011;Kharb et al, 2012;Asif, 2015;Brito et al, 2019). 1-(4-Methoxyphenyl)piperazine has been found to inhibit the re-uptake and accelerate the release of monoamine neurotransmitters such as dopamine and serotonin, with a mechanism of action similar to that of recreational drugs such as amphetamines, but with significantly lower abuse potential (Nagai et al, 2007).…”