The Design and Synthesis of 1,4-Substituted Piperazine Derivatives as Triple Reuptake Inhibitors

Han, Minsoo; Han, Young-Hue; Song, Chi-Man; Hahn, Hoh‐Gyu

doi:10.5012/bkcs.2012.33.8.2597

Cited by 9 publications

(19 citation statements)

References 22 publications

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“…Han et al. synthesized two different series of a total of 49 1,4‐disubstituted piperazine derivatives as triple reuptake inhibitors with antidepressant activity [80] . The antidepressant activity of synthesized compounds was evaluated using neurotransmitter transporter uptake assay kit (Molecular Devices, Sunnyvale, CA, USA) against dopamine (DA), norepinephrine (NE), and serotonin neurotransmitters.…”

Section: Recent Advancements In Piperazine Derivatives As Antidepressantsmentioning

confidence: 99%

Piperazine, a Key Substructure for Antidepressants: Its Role in Developments and Structure‐Activity Relationships

et al. 2021

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Depression is the single largest contributor to global disability with a huge economic and social burden on the world. There are a number of antidepressant drugs on the market, but treatment‐resistant depression and relapse of depression in a large number of patients have increased problems for clinicians. One peculiarity observed in most of the marketed antidepressants is the presence of a piperazine substructure. Although piperazine is also used in the optimization of other pharmacological agents, it is almost extensively used for the development of novel antidepressants. One common understanding is that this is due to its favorable CNS pharmacokinetic profile; however, in the case of antidepressants, piperazine plays a much bigger role and is involved in specific binding conformations of these agents. Therefore, in this review, a critical analysis of the significance of the piperazine moiety in the development of antidepressants has been performed. An overview of current developments in the designing and synthesis of piperazine‐based antidepressants (2015 onwards) along with SAR studies is also provided. The various piperazine‐based therapeutic agents in early‐ or late‐phase human testing for depression are also discussed. The preclinical compounds discussed in this review will help researchers understand how piperazine actually influences the design and development of novel antidepressant compounds. The SAR studies discussed will provide crucial clues about the structural features and optimizations required to enhance the efficacy and potency of piperazine‐based antidepressants.

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Section: Recent Advancements In Piperazine Derivatives As Antidepressantsmentioning

confidence: 99%

Piperazine, a Key Substructure for Antidepressants: Its Role in Developments and Structure‐Activity Relationships

et al. 2021

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“…5H,5xCH). 13 C NMR (101 MHz, DMSO-d 6 ) δ 158. 11, 157.04, 156.33, 155.82, 143.99, 130.17, 128.48, 123.82, 119.05, 96.95 …”

Section: -(4-phenoxyphenyl)-1h-pyrazolo[34-d]pyrimidin-4-amine (11)mentioning

confidence: 99%

“…1 H NMR (400 MHz, CDCl 3 ) δ 7.36 -7.28 (m, 5H, CH ar ), 5.12 (s, 2H, CH 2 ), 3.51 (t, J = 4.8 Hz, 4H, 2xCH 2 ), 2.79 (t, J = 6.0 Hz, 2H, CH 2 ), 2.44 (t, J = 6.0 Hz, 2H, CH 2 ), 2.40 (br s, 4H, 2xCH 2 ), 2.30 (s, 2H, NH 2 ). 13 After the solution of the carboxylate product (12.58 g, 47.75 mmol) in THF (200 mL) was cooled to 0 °C, Boc 2 O (1.2 eq., 12.51 g, 57.30 mmol) was added portion wise and the reaction mixture was allowed to warm up to RT overnight before being concentrated. The residue was further purified by silica column chromatography (20% 30% EtOAc/Pentane) to afford benzyl 4-(2-((tertbutoxycarbonyl)amino)ethyl)piperazine-1-carboxylate as a yellowish oil (13.71 g, 37.72 mmol, 79%).…”

Section: Tert-butyl (2-(piperazin-1-yl)ethyl)carbamate (16)mentioning

confidence: 99%

Direct and two-step bioorthogonal probes for Bruton's tyrosine kinase based on ibrutinib: a comparative study

Liu

Hoogendoorn

Kar³

et al. 2015

Org. Biomol. Chem.

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Ibrutinib is a covalent and irreversible inhibitor of Bruton's tyrosine kinase (BTK) and has been approved for the treatment of haematological malignancies, such as chronic lymphocytic leukaemia, mantle cell lymphoma and Waldenström's macroglobulinemia. The covalent and irreversible nature of its molecular mode of action allows identification and monitoring of its target in an activity-based protein profiling (ABPP) setting. Fluorescent and biotinylated ibrutinib derivatives have appeared in the literature in recent years to monitor BTK in vitro and in situ. The work described here complements this existing methodology and pertains a comparative study on the efficacy of direct and two-step bioorthogonal ABPP of BTK.

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“…Piperazine derivatives are known to possess the properties of triple reuptake inhibitors [1], norovirus inhibitors [2], cannabinoid CB1 receptor agonists [3], antagonists for the melanocortin-4 receptor [4], antimicrobials [5], enzyme inhibitors [6], etc. This moiety has also found applications in the field of engineering [7] and polymers [8].…”

Section: Introductionmentioning

confidence: 99%

“…A Jasco-320-A spectrometer was used to record IR peaks by the KBr pellet method. Bruker spectrometers were used to record 1 H-NMR signals at 500 MHz in CHCl 3 -d 1 , and a JMS-HX-110 spectrometer recorded EIMS signals.…”

Section: Experimental Generalmentioning

confidence: 99%

Synthesis of 3-[4-(2-furoyl)-1-piperazinyl]-N- (substituted)propanamides as promising antibacterial agents with mild cytotoxicity

et al. 2018

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Purpose: To evaluate the antibacterial activity and cytotoxicity of a series of molecules with amalgamation of furoyl, piperazine and amide moieties. Methods: New derivatives, namely 3-[4-(2-furoyl)-1-piperazinyl]-N-(substituted)propanamides, were synthesized and evaluated for their antibacterial activity and toxicity to mammalian cells. The synthesis was initiated by treating different aryl/aralkyl amines (1a-u) with 3-bromopropionyl chloride (2) to obtain the solid electrophiles 3a-u, which were collected by filtration. Thereafter, and 2-furoyl-1-piperazine (4) at equimolar ratios were allowed to react in acetonitrile and in the presence of a base, K2CO3, to form the target compounds, 5a-u. Structural elucidation was carried out using EI-MS (electron impact mass spectrometry), IR (infrared) and 1H-NMR (proton nuclear magnetic resonance). The antibacterial activity of the synthesized compounds was evaluated against various bacterial strains. Furthermore, hemolysis was determined to assess cytotoxicity using bovine red blood cells. Results: Molecules 5g, 5a, 5p, 5g and 5i were found to be potent agents against S. aureus, S. typhi, P. 8.34 ± 0.55, 8.37 ± 0.12, 8.65 ± 0.57, 8.97 ± 0.12 and 9.24 ± 0.50 µM, compared to 7.80 ± 0.19, 7.45 ± 0.58, 7.14 ± 0.58, 7.16 ± 0.58 and 7.29 ± 0.90 aeruginosa, E. coli and B. subtilis with respective minimum inhibitory concentration (MIC) values of

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The Design and Synthesis of 1,4-Substituted Piperazine Derivatives as Triple Reuptake Inhibitors

Cited by 9 publications

References 22 publications

Piperazine, a Key Substructure for Antidepressants: Its Role in Developments and Structure‐Activity Relationships

Piperazine, a Key Substructure for Antidepressants: Its Role in Developments and Structure‐Activity Relationships

Direct and two-step bioorthogonal probes for Bruton's tyrosine kinase based on ibrutinib: a comparative study

Synthesis of 3-[4-(2-furoyl)-1-piperazinyl]-N- (substituted)propanamides as promising antibacterial agents with mild cytotoxicity

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