Synthesis, molecular modeling studies and selective inhibitory activity against MAO of N1-propanoyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives

Franco Chimenti; Rossella Fioravanti; Adriana Bolasco; Fedele Manna; Paola Chimenti; Daniela Secci; Francesca Rossi; Paola Turini; Francesco Ortuso; Stefano Alcaro; Maria Cristina Cardia

doi:10.1016/j.ejmech.2007.12.026

Synthesis, molecular modeling studies and selective inhibitory activity against MAO of N1-propanoyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives

Eur J Med Chem. 2008 Oct;43(10):2262-7. doi: 10.1016/j.ejmech.2007.12.026. Epub 2008 Jan 6.

Authors

Franco Chimenti¹, Rossella Fioravanti, Adriana Bolasco, Fedele Manna, Paola Chimenti, Daniela Secci, Francesca Rossi, Paola Turini, Francesco Ortuso, Stefano Alcaro, Maria Cristina Cardia

Affiliation

¹ Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università La Sapienza, P.le Aldo Moro 5, 00185 Rome, Italy.

PMID: 18281126
DOI: 10.1016/j.ejmech.2007.12.026

Abstract

A series of N1-propanoyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives were synthesized and assayed as inhibitors of MAO-A and MAO-B isoforms. Most of the tested compounds showed inhibitory activity with micromolar values and MAO-A selectivity. In addition a computational work was carried out on the most selective compound 3b to highlight the most relevant interactions in the mechanism of recognition within both the MAO-A and the MAO-B enzyme active sites.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cattle
Drug Design
Humans
Models, Molecular*
Molecular Conformation
Monoamine Oxidase / chemistry*
Monoamine Oxidase / metabolism
Monoamine Oxidase Inhibitors / chemical synthesis*
Monoamine Oxidase Inhibitors / chemistry
Monoamine Oxidase Inhibitors / pharmacology*
Pyrazoles / chemical synthesis*
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Substrate Specificity

Substances

Monoamine Oxidase Inhibitors
Pyrazoles
Monoamine Oxidase