Molecular structure analysis of benzamide neuroleptics. Part 13. A tropapride sulphonamidic analogue C₁₅H₂₂N ₃O₃SCI

The crystal structure of the title compound (1 ) has been solved by direct methods from single crystal X-ray diffraction. Monoclinic, space group P2 ₁/c with a = 9.277(1), b = 9.977(2), c = 18.557(2) Å, β = 98.44(1)°; Z = 4. The final R-factor is 0.03 for 2923 observed reflections. The inactive title compound (for the dopaminergic D₂ receptor) containing a benzosulphonamide function is compared with a very potent benzamide analogue: tropapride (2). The molecular conformation of the title compound obtained by optimal superimposition (flexible fitting) of the proposed pharmacophoric elements with those of tropapride corresponds to a significantly less stable conformation as shown by ab initio LCAO-MO-SCF calculations. In fact, the electron-attracting mesomeric effect of the sulphone group excludes the formation of a strong intramolecular hydrogen bond which would stabilize the tropapride-like conformation of the lateral chain.