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Licit and illicit drugs
Published in Jason Payne-James, Richard Jones, Simpson's Forensic Medicine, 2019
Jason Payne-James, Richard Jones
Many of these newly abused drugs belong to the chemical class known as piperazines, derived from piperazine and benzyl chloride. Piperazines were originally used as worming agents in humans and in veterinary medicine, particularly in the treatment of round worms (especially Ascaris); they paralyse the worms so they are flushed out by peristalsis. However, the medicinal use of piperazines is banned in many countries. Ironically, more than half of the cocaine sold in the USA is contaminated with levamisole, a piperazine anti-helminthic drug, which was initially withdrawn from the US market because it is known to induce bone marrow suppression. Several piperazines derivatives are now in circulation.
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
The piperazines are a type of DRUG (for example, FLUPHENAZINE and TRIFLUOPERAZINE) related to the PHENOTHIAZINES, with ANTIPSYCHOTIC activity. They have quite significant EXTRAPYRAMIDAL SIDE-EFFECTS and are not commonly used.
Discovery of novel arylamide derivatives containing piperazine moiety as inhibitors of tubulin polymerisation with potent liver cancer inhibitory activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Xiao-Yi Shi, Huang Jiao, Jia-Kai Zhang, Xin-Yi Tian, Dan-Feng Guo, Jie Gao, Mei-Qi Jia, Jian Song, Sai-Yang Zhang, Xiang-Jing Fu, Hong-Wei Tang
We further explored the effects of replacement of aryl piperazine groups with alkyl piperazines, carbonyl piperazines, morpholine, or thiomorpholine on the antiproliferative activities. As shown in Table 2, the target compounds 16l–16s exhibited reduced antiproliferative activities with IC50 values ranging from 0.88 to 6.69 μM than that of compounds 16a–16k. Among them, compound 16l bearing the 1-methylpiperazine group exhibited the most potent inhibitory activities with IC50 values of 1.21 (for MGC-803), 0.88 (for HCT-116), and 1.58 μM (for SMMC-7721). Comparing the antiproliferative activities of compounds 16l–16s, it was obvious to figure out that the compounds 16l–16o bearing the alkyl piperazines were more effective in inhibiting the proliferation of cancer cells than that of compounds 16p–16s bearing the carbonyl piperazines (compounds 16p–16q), morpholine (compound 16r), or thiomorpholine (compound 16s). In addition, the extension of alkyl chains (compounds 16l–16o) reduced inhibitory activities.
The piperazine scaffold for novel drug discovery efforts: the evidence to date
Published in Expert Opinion on Drug Discovery, 2022
Maria Novella Romanelli, Dina Manetti, Laura Braconi, Silvia Dei, Alessio Gabellini, Elisabetta Teodori
The widespread insertion of a piperazine moiety into drugs is due to its physicochemical properties. Piperazine 20 (Table 2) contains two basic nitrogen atoms; however, at physiological pH (7.4), only one is protonated (pKa values 9.75 and 5.36) [18]). The basicity of substituted piperazines varies according to the position and nature of the substituent. In fact, 20 becomes less basic after alkylation of one carbon atom (20a) and of one (20b, 20c) or of both nitrogen atoms (20d) [19]. The insertion of acyl (20e-h) or sulfonyl (20i) substituents, or of aromatic rings (20 j-l), is also detrimental [20–22]: the pKa variation depends on the kind of aryl group and the substituent on the aromatic ring [20,21]. The reduction of basicity after alkylation of one of the N atoms was verified also in other situations [20,22]. For instance, we can compare the pKa of 20f and 20h or 20j and 20k. The basicity obviously affects the degree of ionization of the molecule, its lipophilicity and solubility, and its ability to establish H-bonds as donor or acceptor, in other words, its drug-like properties.
Investigation of piperazines as human carbonic anhydrase I, II, IV and VII activators
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Andrea Angeli, Niccolò Chiaramonte, Dina Manetti, Maria Novella Romanelli, Claudiu T. Supuran
Piperazines 1–24 (Figure 3) were chosen to be investigated as CAAs as they contain the endocyclic NH group able to participate in proton shuttling processes between the zinc-coordinated water from the CA active site and the external medium, in a similar manner to 4-aminoethyl-piperazine A, and histamine B, which were considered as lead compounds. Furthermore, in contrast to A and B, piperazines 1–24 do not possess the aminoethyl moiety present in the two leads, but the pKa of the NH (or NR) groups from the heterocyclic ring is influenced by the diverse substitution patterns present in them. Indeed, both electron withdrawing as well as electron donating moieties are present in these compounds which may lead to a different basicity of the moieties able to shuttle protons between the enzyme active site and the reaction medium (Figure 3). The unsubstituted piperazine (compound C) was also tested for comparison.