STRUCTURE AND MOLECULAR-PROPERTIES OF (1)-CENTBUTINDOLE - COMPARISON WITH HALOPERIDOL

The structure and conformation of (1)-Centbutindole, a newly marketed neuroleptic compound, has been investigated by X-ray crystallography. It crystallizes in the monoclinic system and the non-centrosymmetric s pace group P2(1) (Z = 2) with cell dimensions a = 8.434(6), b = 6.620( 3), c = 18.419(9)Angstrom, and beta = 95.07(6)degrees. The chain confo rmation is trans extended. The embedded Delta(3) piperidine ring exist s in a half-chair conformation whereas the embedded piperazine ring ex ists in a chair conformation. The propylene side chain is equatorial r elative to the piperazine. A systematic conformational analysis of cen tbutindole and of a related molecule, Haloperidol, followed by a Monte Carlo search and a stochastic dynamics simulation, have been performe d. Electronic and lipophilic properties have been computed and, molecu lar electrostatic potential (MEP) maps and molecular lipophilicity pot ential (MLP) maps, have been displayed for two selected conformers sat isfying a reported pharmacophore. The two molecules exhibit very simil ar molecular properties.