Monoamine oxidase inhibitory activity of 3,5-biaryl-4,5-dihydro-1H-pyrazole-1-carboxylate derivatives

• 3a–3f were competitive, reversible inhibitors & selective inhibitors of hMAO-A.
• Phenyl carbamates (3e–3h) were potent with best selectivity index towards hMAO-A.
• Molecular docking studies revealed that S-conformers were better than R-conformers.
• Compound 3f, the best amongst the eight with SIhMAO-A = 8.86 × 10−5.

Ethyl and phenyl carbamate derivatives of pyrazoline (3a–3h) were synthesized and tested for their MAO inhibitory activity. All the compounds were found to be selective towards MAO-A. Phenyl carbamates (3e–3h) were better than ethyl carbamates (3a–3d) and displayed the best selectivity index. Compound 3f (KiMAO-A; 4.96 ± 0.21 nM) was found to be equally potent as that of standard drug, Moclobemide (KiMAO-A; 5.01 ± 0.13 nM) but with best selectivity index (8.86 × 10−5). Molecular docking studies with R & S conformer of 3f revealed S-enantiomer is better than R-enantiomer as reported earlier by other groups. It is proposed that VdW's radii of the substitution (bulkiness) in ring B determine the potency of phenyl carbamates.

Amongst the eight compounds (3a–3h), compound 3f was found to be potent and selective towards hMAO-A and is competitive and reversible in nature.Figure optionsDownload as PowerPoint slide