5-Aryl-1,3,4-oxadiazol-2(3H)-one derivatives and sulfur analogues as new selective and competitive monoamine oxidase type B inhibitors

Mazouz, Fathi; Lebreton, Luc; Milcent, René; Burstein, Claude

doi:10.1016/0223-5234(90)90131-l

Cited by 43 publications

(18 citation statements)

References 24 publications

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“…The only current drug marketed for reversible inhibition of MAO A is moclobemide [ 65 ]. The anti-bacterial drug linezolid is a weak inhibitor [ 66 ], but many other oxazolidinones are potent reversible inhibitors of MAO [ 67 , 68 ], including the MAO-A selective inhibitor befloxatone [ 69 ]. The need to avoid inhibiting MAO A in the gut and the increase of MAO B in ageing brain has driven the search for potent reversible inhibitors of MAO B. Safinamide, an anticonvulsant now marketed for Parkinson’s disease, is an inhibitor of MAO B that is effective at nanomolar concentrations [ 70 ].…”

Section: Inhibition Of Neurotransmitter Breakdown In Neurodegeneramentioning

confidence: 99%

Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs

2017

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The actions of many drugs involve enzyme inhibition. This is exemplified by the inhibitors of monoamine oxidases (MAO) and the cholinsterases (ChE) that have been used for several pharmacological purposes. This review describes key principles and approaches for the reliable determination of enzyme activities and inhibition as well as some of the methods that are in current use for such studies with these two enzymes. Their applicability and potential pitfalls arising from their inappropriate use are discussed. Since inhibitor potency is frequently assessed in terms of the quantity necessary to give 50% inhibition (the IC50 value), the relationships between this and the mode of inhibition is also considered, in terms of the misleading information that it may provide. Incorporation of more than one functionality into the same molecule to give a multi-target-directed ligands (MTDLs) requires careful assessment to ensure that the specific target effects are not significantly altered and that the kinetic behavior remains as favourable with the MTDL as it does with the individual components. Such factors will be considered in terms of recently developed MTDLs that combine MAO and ChE inhibitory functions.

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Section: Inhibition Of Neurotransmitter Breakdown In Neurodegeneramentioning

confidence: 99%

Assessment of Enzyme Inhibition: A Review with Examples from the Development of Monoamine Oxidase and Cholinesterase Inhibitory Drugs

2017

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“…10; fragment I) established from the study of several families of reversible and selective monoamine oxidase inhibitors (oxadiazolones, tetrazoles and oxadiazinones derivatives so-called diazoheterocyclics) [94][95][96][97] has been used in a 3D-search of the CSD to identify new lead compounds [98].…”

Section: Example 13mentioning

confidence: 99%

Small Molecule Crystallography in Drug Design

Ooms

2001

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Crystal structures of small molecules (i.e. isolated ligands) are a source of valuable structural information helpful in the process of drug design (pharmacophore model elaborations, 3D QSAR, docking, and de novo design). Indeed, structural data obtained from small molecules crystallography can approach ligand-receptor binding by providing unique structural features both about the conformation (internal geometry) of the ligand (s) and about the intermolecular interaction potentially occurring within the active site of a target (enzyme/receptor). Small molecule crystal structure databases can also be used in three dimensional search to identify new drug candidates. Future development in small molecule crystallography (e.g. powder diffraction) should also provide original solutions to complex problems related to polymorphism.

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“…The compounds 1,3,4-oxadiazole heterocycles are good bioisosteres of amides and esters, which can contribute substantially in increasing pharmacological activity by participating in hydrogen bonding interactions with the receptors [3]. The 2,5-disubstituted-1,3,4-oxadiazole derivatives are known for various pharmacological activities such as antibacterial [4], anti-inflammatory [5], analgesic [6], antiviral and anticancer [7], antihypertensive [8], anticonvulsant [9], antiproliferative [10], herbicidal [11], hypoglycemic [12], hypnotic and sedative [13], MAO inhibitor [14] and insecticidal [15].…”

Section: Introductionmentioning

confidence: 99%