Molecular structure analysis of benzamide neuroleptics. Part 13. A tropapride sulphonamidic analogue C15H22N3O3SCl

Abstract

The crystal structure of the title compound (1) has been solved by direct methods from single crystal X-ray diffraction. Monoclinic, space group P21/c with a= 9.277(1), b= 9.977(2), c= 18.557(2)A, β= 98.44(1)°; Z= 4. The final R-factor is 0.03 for 2 923 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.