Morpholine as a privileged scaffold for neurodegenerative disease therapeutics

Морфолин как привилегированная структурная платформа для создания лекарственных средств против нейродегенеративных заболеваний
Saranya Kattil Parmbil, Sunil Kumar, T. M. Rangarajan, Della Grace Thomas Parambi, Naseer Maliyakkal, Anél Petzer, Jacobus P. Petzer, Bijo Mathew
2026-01-01

blood-brain barrier permeabilitycholinesterase inhibitorsmonoamine oxidase inhibitorsmorpholine derivativesneurodegenerative diseases
Morpholine, a six-membered heterocyclic ring containing oxygen and nitrogen, is increasingly recognized in medicinal chemistry for its diverse pharmacological properties. Morpholine derivatives have shown promise as enzyme inhibitors, neurotransmitter modulators, and receptor agonists, making them candidates for treating neurodegenerative and neuropsychiatric disorders. The importance of this study lies in elucidating the therapeutic significance of morpholine in central nervous system (CNS) drug development, particularly in its role in inhibiting monoamine oxidases (MAO-A and MAO-B) and cholinesterases (AChE and BChE) and targeting the norepinephrine and dopamine pathways. Systematic searches of peer-reviewed literature were conducted to evaluate the structural significance and pharmacological potential of morpholine-based compounds. The findings reveal that morpholine derivatives exhibit promising efficacy and selectivity, often outperforming conventional drugs in specific contexts. These discoveries point to the possibility of morpholine as a valuable scaffold in CNS drug discovery due to its balanced lipophilic-hydrophilic profile and enhanced blood-brain barrier permeability. The implications of these findings are significant, and they call for future research to focus on optimizing morpholine derivatives to improve selectivity, efficacy, and safety, thereby expanding their therapeutic potential in CNS applications. Overall, this study emphasizes the importance of morpholine derivatives in advancing CNS therapeutics and their potential role in addressing unmet medical needs in neuropsychiatric disorder treatments.
1
Morpholine derivatives show potential as inhibitors of monoamine oxidases MAO-A and MAO-B and cholinesterases AChE and BChE.
2
Morpholine is identified as a promising privileged scaffold for central nervous system drug development because of its diverse pharmacological properties.
3
Morpholine’s balanced lipophilic-hydrophilic profile may enhance blood-brain barrier permeability, while further optimization is needed to improve selectivity, efficacy, and safety.
4
Reported morpholine derivatives demonstrate promising efficacy and selectivity, in some contexts outperforming conventional drugs.
5
These compounds can modulate neurotransmitter systems, including norepinephrine and dopamine pathways, relevant to neurodegenerative and neuropsychiatric disorders.

morpholine derivatives for central nervous system therapeutics

their pharmacological efficacy and selectivity in inhibiting monoamine oxidases and cholinesterases and modulating norepinephrine and dopamine pathways

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2026-01-01
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Saranya Kattil Parmbil
Sunil Kumar
T. M. Rangarajan
Della Grace Thomas Parambi
Naseer Maliyakkal
Anél Petzer
Jacobus P. Petzer
Bijo Mathew
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