Revealing the role of the benzyloxy pharmacophore in the design of a new class of monoamine oxidase‐B inhibitors

Abstract

The conceptual layout of monoamine oxidase (MAO) inhibitors has been modified to explore their potential biological application in the case of neurological disorders for the time being. The current review article is an effort to display the summation of innovative conceptual prospects of MAO inhibitors and their intriguing chemistry and bioactivity. Based on this scenario, we emphasize the pivotal role of the benzyloxy moiety attached to scaffolds like oxadiazolones, indolalkylamines, safinamide, caffeine, benzofurans, α-tetralones, β-nitrostyrene, benzoquinones, coumarins, indoles, chromones, and chromanone analogs, while acting as an MAO inhibitor.

Exploration of a new class of monoamine oxidase B inhibitors by assembling benzyloxy pharmacophore on halogenated chalcones

“…The moieties associated to the benzyloxy group, such as indolalkylamines, nitrostyrene, safinamide, oxadiazolones, benzofurans, benzoquinones, coumarins, caffeines, indoles, tetralones, chromanone and chromones analogues, exhibit substantial MAO‐B inhibiting activities. When acting as a MAO inhibitor, the benzyloxy group attached to some frameworks reinforced the importance of a conformationally flexible terminus phenyl, which was then strengthened by adding a conformationally pliable ‐CH 2 O‐ bridge (Chimenti et al, 2009; Knez et al, 2022; Mostert et al, 2017; Pérez et al, 1999; Rao et al, 2021; Rullo et al, 2019; Sudevan, Rangarajan, et al, 2022).…”

2‐Hydroxy‐4‐benzyloxylimine Resveratrol Derivatives as Potential Multifunctional Agents for the Treatment of Parkinson's Disease

“…Moreover, aryl benzyl ether is a versatile scaffold, many natural products and synthetic derivatives with this pharmacophore showed various activities such as MAO-B inhibition, antioxidant activity, glutamate release inhibition and neuroprotective effects. [29][30][31] Especially, the representative compound safinamide, which was approved by European Medicines Agency (EMA) for the treatment of PD in 2015, is a typical MAO-B inhibitor with multiple biologic functions. [32] Therefore, in order to obtain novel multifunctional anti-PD agents with more efficiency, imine resveratrols with ortho hydroxy group were combined with aryl benzyl ether in this paper to afford a series of 2-hydroxy-4-benzyloxyimine resveratrol derivatives by using MTDLs strategy (Figure 2).…”

“…Moreover, aryl benzyl ether is a versatile scaffold, many natural products and synthetic derivatives with this pharmacophore showed various activities such as MAO‐B inhibition, antioxidant activity, glutamate release inhibition and neuroprotective effects [29–31] . Especially, the representative compound safinamide, which was approved by European Medicines Agency (EMA) for the treatment of PD in 2015, is a typical MAO‐B inhibitor with multiple biologic functions [32] .…”

Piperidine: A Versatile Heterocyclic Ring for Developing Monoamine Oxidase Inhibitors

“…47 Currently, Food and Drug Administration (FDA)-approved drugs, such as antipsychotics, include haloperidol, 48 benperidol, 49 risperidone, 50 and thioridazine 51 for the symptomatic management of schizophrenia; droperidol, a dopamine antagonist used to prevent and treat postoperative nausea and vomiting; 52 and anticholinesterases, including donepezil 53 for treating AD (Figure 3). 26 Recently, many structural scaffolds, such as chalcones, 54 conjugated dienones, 55 isatins, 56 chromones, 57 coumarins, 58 pyrazolines, 59 quinazolines, 60 β-carbolines, 61 and benzyloxyderived molecules, 62 are used to develop MAO inhibitors. In search for newer MAO inhibitors, researchers have identified the inevitable role of halogens in selective and potent MAO-B inhibition.…”