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

• Published in: European journal of medicinal chemistry Vol. 43; no. 10; pp. 2262 - 2267
• Main Authors: Chimenti, Franco, Fioravanti, Rossella, Bolasco, Adriana, Manna, Fedele, Chimenti, Paola, Secci, Daniela, Rossi, Francesca, Turini, Paola, Ortuso, Francesco, Alcaro, Stefano, Cardia, Maria Cristina
• Format: Journal Article
• Language: English
• Published: PARIS Elsevier Masson SAS 01.10.2008; Elsevier
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Biological and medical sciences; Cattle; Chemistry, Medicinal; Drug Design; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Life Sciences & Biomedicine; MAO inhibitors; Medical sciences; Miscellaneous; Models, Molecular; Molecular Conformation; Molecular modeling; Monoamine Oxidase - chemistry; Monoamine Oxidase - metabolism; Monoamine Oxidase Inhibitors - chemical synthesis; Monoamine Oxidase Inhibitors - chemistry; Monoamine Oxidase Inhibitors - pharmacology; Oxidoreductases; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrazoline derivatives; Science & Technology; Substrate Specificity; Pyrazoline derivatives; MAO inhibitors; Molecular modeling; MONOAMINE-OXIDASE; DRUG; DOCKING; NEURONS; SELEGILINE; FORCE-FIELD; BRAIN; Five membered ring; Enzyme; Nitrogen heterocycle; Isozyme; MAO inhibitor; Benzene derivatives; Enzyme inhibitor; Inhibitor enzyme complex; Selectivity; In vitro; Modeling; Amine oxidase (flavin-containing); Structure activity relation; Molecular model; Oxidoreductases; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2007.12.026

A series of N1-propanoyl-3,5-diphenyl-4,5-dihydro-(1 H)-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. A series of N1-propanoyl-3,5-diphenyl-4,5-dihydro-(1 H)-pyrazole derivatives were synthesized and assayed as inhibitors of MAO-A and MAO-B isoforms. [Display omitted]