Section 13
Chapter 12,612

Synthesis and molecular modelling of novel substituted-4,5-dihydro- (1H) -pyrazole derivatives as potent and highly selective monoamine oxidase-A inhibitors

Chimenti, F.; Bolasco, A.; Manna, F.; Secci, D.; Chimenti, P.; Granese, A.; Befani, O.; Turini, P.; Alcaro, S.; Ortuso, F.

Chemical Biology and Drug Design 67(3): 206-214


ISSN/ISBN: 1747-0277
PMID: 16611214
DOI: 10.1111/j.1747-0285.2006.00367.x
Accession: 012611231

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This report describes novel pyrazoline derivatives investigated for their ability to selectively inhibit the activity of the A and B isoforms of monoamine oxidase. These new synthetic compounds proved to be reversible, potent, and selective inhibitors of monoamine oxidase-A rather than of monoamine oxidase-B, and are promising candidates to further advance drug discovery efforts. The most active compounds show inhibitory activity on monoamine oxidase-A in the 1.0x10(-8)-8.6x10(-9) M range. Moreover, it should be pointed out that for some compounds a high IC50>or=10(-9) M value is associated with a high A-selectivity (Selectivity Index monoamine oxidase-B/monoamine oxidase-A in the 10,000-12,500 range). Further insight to understand enzyme-inhibitor molecular interaction was obtained by docking experiments with the monoamine oxidase-A and monoamine oxidase-B isoforms.

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