A series of 2-methoxy-4-(5-phenyl-4,5-dihydro-1-pyrazol-3-yl)phenol (pyrazoline) derivatives () have been synthesized and tested for human monoamine oxidase (hMAO) inhibitory activity. The most active derivative () behaved as a competitive hMAO-A inhibitor, with an inhibition constant value of 0.08 μM and a strong hMAO-A selectivity ((hMAO-B)/(hMAO-A) > 1751). In addition, exhibited little to no cytotoxic effects up to a 25 μM concentration and provided the best blood-brain barrier permeability among the derivatives synthesized. Molecular dynamics simulations revealed that a chlorine substituent at the-position of the phenyl ring in enabled a π-π stacking interaction with Tyr407 and Tyr444 that resulted in the formation of an "aromatic sandwich" structure. Consequently, this tight-binding aromatic cage culminated in a dramatically reduced active site volume that is believed to be the origin of the observed selectivity between the hMAO-A and hMAO-B isozymes. Removal of the chlorine from disrupted the favorable intermolecular interactions and resulted in a selectivity change towards hMAO-B.

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Die aus Indol‐3‐aldehyd (I) mit den Phenylhydrazinen (II) leicht zugänglichen Phenylhydrazone (III) kuppeln mit den Aryldiazoniumchloriden (IV) zu den Formazanen (V), die sich mit H2O2 zu den Tetrazoliumsalzen (VI) cyclisieren lassen.