Synthesis and antidepressant-like activity evaluation of sulphonamides and sulphonyl-hydrazones.

In this study a series of sulphonamides and sulphonyl hydrazones of maleimide, naphthalimide and phthalimide derivatives was synthesized. The antidepressant effect of these compounds was evaluated by the forced-swimming test in mice. The behavioural parameter observed in this test is a reduction in the immobility time, which is indicative of antidepressant activity. All compounds, except 8, 11 and 24, were active as antidepressants. The most active compound was the sulphonyl-hydrazone 10 which showed an activity of around 72.02% at 60 mg/kg, it thus being more active than imipramine (10mg/kg, ip), a commercial antidepressant. Other important results were obtained for the benzylnaphthalimide derivatives, the sulphonamides 21 and 22 showing activity of 64% at 10mg/kg, also being more active than imipramine. These results indicate that the sulphonamides and sulphonyl-hydrazone cyclic imide derivatives are potential compounds for use in the designing of new candidates for the treatment of depression.

4-[(1,3-Dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-2-yl)meth-yl]-N'-[(E)-4-nitro-benzyl-idene]benzene-sulfono-hydrazide dimethyl sulfoxide monosolvate.

The mol-ecular structure of the title compound, C(26)H(18)N(4)O(6)S·C(2)H(6)OS, shows an E conformation of the hydrazone double bond. The presence of a methyl-ene group between the benzo[de]isoquinoline and benzene-sulfonyl moieties allows the 4-nitro-phenyl ring and the benzo[de]isoquinoline system to be parallel with respect to each other, so that the mol-ecule adopts a U-shaped spatial conformation. The dihedral angle between mean planes of these aromatic groups is 4.4 (1)°. This special arrangement enables neighboring mol-ecules to be inter-calated, forming slipped π-π inter-actions [centroid-centroid distance = 3.535 (2) Å] between the 4-nitro-phenyl and benzo[de]isoquinoline groups and point-to-face C-H⋯π inter-actions between the benzo[de]isoquinoline and benzene-sulfonyl aromatic systems. In addition, the crystal packing also features an inter-molecular N-H⋯O inter-action involving the amine group and the dimethyl sulfoxide solvent mol-ecule.

Antinociceptive properties of chloromaleinimides and their sulphonyl derivatives.

This report describes the synthesis of new cyclic imides obtained from the reaction between aniline and dichloromaleic anhydride with further chlorosulphonation as well as the reaction between different amines and 4-methoxyphenol for the synthesis of imidobenzenesulphonyl derivatives. These compounds were tested as antinociceptive agents using the writhing test on mice. Some compounds, when intraperitoneally injected, proved to be potent and dose-related antinociceptives, being several times more active than many known reference drugs.