Structure-activity relationship of a new series of tricyclic monoamine oxidase inhibitors of pentanthrene type.

Abstract

This study was undertaken to evaluate the relationship between the structure and monoamine oxidase (MAO) inhibitory activity of a new series of tricyclic compounds, represented by tetrazolo-[5, 1-a]phthalazine (Tetra-P), which are based on the pentanthrene skeleton (Fig. 1.). Eleven tricyclic compounds analogous to Tetra-P were synthesized and tested as MAO inhibitors in vitro. Some of them, 1, 2, 3-triazolo[1, 5-a]quinoline (Tri-Q), tetrazolo[5, 1-a]isoquinoline (Tetra-I), 1, 2, 3-triazolo-[5, 1-a]isoquinoline (Tri-I2) and 1H-naphtho[1, 2-d]triazole (Tri-N), were found to have potent MAO inhibitory effects almost equal to that of iproniazid or nialamide. In this series of compounds, the addition of the C ring to the bicyclic skeleton seemed to produce an increase in MAO inhibitory potency compared with the corresponding bicyclic compounds. The sequence of nitrogen atoms of the C ring appeared to be important for the MAO inhibitory effect. It was concluded that the electronic conditions around the C ring are critical for the interaction between MAO and these inhibitors.