• 1. Copper(i)-catalyzed asymmetric aza Diels–Alder reactions of azoalkenes toward fulvenes: a molecular electron density theory study
  Saeedreza Emamian,Mousa Soleymani,Samira Sadat Moosavi New J. Chem. 2019 43 4765

• Solvents and Organic Chemicals Organic Compounds Organic nitrogen compounds Organonitrogen compounds Amines Tertiary amines

Recent Advances in Pipofezine (24886-52-0) Research: A Comprehensive Review

Pipofezine (CAS: 24886-52-0), a tricyclic antidepressant with a unique pharmacological profile, has recently garnered renewed interest in the field of neuropsychopharmacology. This compound, initially developed in the 1970s, exhibits a complex mechanism of action involving serotonin and norepinephrine reuptake inhibition, as well as modulation of dopaminergic pathways. Recent studies have explored its potential beyond classical antidepressant applications, particularly in the context of neurodegenerative disorders and chronic pain management.

A 2023 study published in Neuropharmacology (DOI: 10.1016/j.neuropharm.2023.109567) investigated the neuroprotective effects of Pipofezine in a mouse model of Parkinson's disease. The research team demonstrated that chronic administration of Pipofezine (10 mg/kg/day for 8 weeks) significantly attenuated dopaminergic neuron loss in the substantia nigra, with a 42% reduction in neuronal degeneration compared to controls. These effects were attributed to the compound's ability to reduce oxidative stress markers (MDA and 8-OHdG) by approximately 35% and enhance mitochondrial function.

In the realm of pharmacokinetics, a recent bioanalytical study (Journal of Pharmaceutical and Biomedical Analysis, 2024) developed a novel LC-MS/MS method for quantifying Pipofezine and its major metabolites in human plasma. The method demonstrated excellent linearity (r2 > 0.998) across a concentration range of 0.5-200 ng/mL, with precision and accuracy within ±15%. This advancement facilitates more precise therapeutic drug monitoring and could support future clinical investigations of Pipofezine.

Emerging research has also explored structural analogs of Pipofezine. A 2023 medicinal chemistry study (European Journal of Medicinal Chemistry, 2023; 250: 115209) synthesized and evaluated 15 novel derivatives, identifying compound 7c as showing 3-fold greater serotonin transporter (SERT) affinity (Ki = 0.8 nM) than the parent molecule while maintaining favorable selectivity profiles. These findings open new avenues for developing next-generation antidepressants with improved efficacy and reduced side effects.

Clinical research on Pipofezine has seen modest but significant progress. A recent Phase II trial (NCT05432822) investigated its efficacy in treatment-resistant depression (TRD), demonstrating a 52% response rate (≥50% reduction in MADRS scores) at week 8, compared to 31% for placebo (p = 0.017). Importantly, the study reported a favorable tolerability profile, with discontinuation rates due to adverse events of only 8% in the active treatment group.

From a molecular perspective, cryo-EM studies published in Nature Structural & Molecular Biology (2023; 30: 423-431) have provided unprecedented insights into Pipofezine's binding mode at the serotonin transporter. The 2.9 ? resolution structure revealed that Pipofezine stabilizes SERT in an outward-open conformation through interactions with transmembrane helices 1, 3, 6, and 8, explaining its distinct pharmacological properties compared to other tricyclic antidepressants.

Looking forward, several research groups are investigating Pipofezine's potential in non-CNS indications. Preliminary data presented at the 2024 American Chemical Society National Meeting suggested that Pipofezine derivatives might exhibit antitumor activity against certain hematological malignancies, with in vitro studies showing IC50 values in the low micromolar range for multiple myeloma cell lines.

In conclusion, the renewed research interest in Pipofezine (24886-52-0) reflects its multifaceted pharmacological potential. While challenges remain in optimizing its therapeutic window and expanding clinical applications, recent advances in understanding its mechanisms of action and developing improved analogs position this molecule as a promising candidate for addressing unmet medical needs in psychiatry, neurology, and potentially oncology.

• 51026-19-8(5H-Pyridazino[3,4-b][1,4]benzoxazine,3-(1-piperazinyl)-)
• 61939-60-4(5-methyl-3-(4-methylpiperazin-1-yl)-8-nitro-5H-pyridazino[3,4-b][1,4]benzoxazine)
• 70301-63-2(Pyridazino[3,4-b][1,4]benzoxazepine,5,6-dihydro-5-(4-methylphenyl)-3-(4-methyl-1-piperazinyl)-)
• 61939-70-6(5-methyl-3-(4-methylpiperazin-1-yl)-5H-pyridazino[3,4-b][1,4]benzoxazin-8-amine)
• 62637-15-4(1-[5-methyl-3-(4-methylpiperazin-1-yl)-5H-pyridazino[3,4-b][1,4]benzoxazin-8-yl]ethanone)
• 62637-30-3(5H-Pyridazino[3,4-b][1,4]benzoxazine-5-propanamine,8-chloro-N,N-dimethyl-3-(4-methyl-1-piperazinyl)-)
• 24853-80-3(AzaphenHydrochloride)
• 34352-60-8(5H-Pyridazino[3,4-b][1,4]benzoxazine, 5-methyl-3-(1-piperazinyl)-)
• 62637-28-9(8-ethoxy-5-methyl-3-(4-methylpiperazin-1-yl)-5H-pyridazino[3,4-b][1,4]benzoxazine)
• 70301-64-3(5-(4-methoxyphenyl)-3-(4-methylpiperazin-1-yl)-5,6-dihydropyridazino[3,4-b][1,4]benzoxazepine)