Selective inhibitors of monoamine oxidase. 2. Arylamide SAR.
Monoamine oxidase (MAO) exists in two forms distinguishable by substrate specificity. Inhibition of MAO A is believed to be responsible for the antidepressant activity of MAO inhibitors. A group of N-arylacetamides are highly specific inhibitors of MAO A, some with IC50 values in the 10-100 nM range. The requirements for high activity and specificity include a nearly linear tricyclic aromatic portion but a larger and a smaller central ring component. The amide group, which is best acetamido, is optimally placed para to the smaller central group. The size and shape of the aromatic moiety appear to be the major influence on activity and specificity for MAO A.
Division of Organic Chemistry, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709.
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Harfenist
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Joyner
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D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology; D002855:Chromatography, Thin Layer; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000081:Acetamides; D000928:Antidepressive Agents; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase