Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. Monoamine oxidase (MAO) is an FAD-containing enzyme bound to the mitochondrial outer membrane of neuronal, glial, and other cells. This enzyme regulates levels of biogenic amines ( including neurotransmitters) in the brain and the peripheral tissues by catalyzing their deamination. The MAOIs have been used for several years in the treatment of depression and anxiety diseases (MAO-A inhibitors) and in Parkinson's disease (MAO-B inhibitors). The benzofuran nucleus has been recently described as a good scaffold for the design of potent and relatively non selective MAOIs. Several 3-arylcoumarin derivatives were previously described as interestings elective MAO-B inhibitors. Preserving the trans stilbene structure, a series of 2-arylbenzofuran derivatives were synthesized and evaluated as inhibitors of both MAO isoforms, MAO-A and MAO-B. The key step for the formation of the benzofuran moiety was achieved by an intramolecular Wittig reaction between ortho-hydroxybenzyltriphosphonium salts and the appropriate benzoyl chlorides.
SYNTHESIS AND BIOLOGICAL EVALUATION OF 2-ARYLBEI\ZOFURANS AS MAO INHIBITORS
DELOGU, GIOVANNA LUCIA;
2014-01-01
Abstract
Monoamine oxidase (MAO) is an important drug target for the treatment of neurological disorders. Monoamine oxidase (MAO) is an FAD-containing enzyme bound to the mitochondrial outer membrane of neuronal, glial, and other cells. This enzyme regulates levels of biogenic amines ( including neurotransmitters) in the brain and the peripheral tissues by catalyzing their deamination. The MAOIs have been used for several years in the treatment of depression and anxiety diseases (MAO-A inhibitors) and in Parkinson's disease (MAO-B inhibitors). The benzofuran nucleus has been recently described as a good scaffold for the design of potent and relatively non selective MAOIs. Several 3-arylcoumarin derivatives were previously described as interestings elective MAO-B inhibitors. Preserving the trans stilbene structure, a series of 2-arylbenzofuran derivatives were synthesized and evaluated as inhibitors of both MAO isoforms, MAO-A and MAO-B. The key step for the formation of the benzofuran moiety was achieved by an intramolecular Wittig reaction between ortho-hydroxybenzyltriphosphonium salts and the appropriate benzoyl chlorides.
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