Inhibition of amine oxidases activity by 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives

A novel series of 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives have been synthesised and investigated for the ability to inhibit selectively monoamine oxidases, swine kidney oxidase, and bovine serum amine oxidase. The newly synthesised compounds 1-6 proved to be reversible and non-competitive inhibitors of all types of the assayed amine oxidases. Compounds inhibit monoamine oxidases potently, displaying low 150 values of particular interest. In particular 1-acetyl-3-(2,4-dihydroxyphenyl)-5-(3-methylphenyl)-4,5-dihydro-(1H)-pyrazole 6 showed to be a potent monoamine oxidase inhibitor with a K-i of about 10(-8) M. Further insights in the theoretical evaluation of the possible interactions between the compounds and monoamine oxidase B have been developed through a computational approach. (C) 2002 Elsevier Science Ltd. All rights reserved.