A COMPARATIVE MOLECULAR-FIELD ANALYSIS MODEL FOR 6-ARYLPYRROLO[2,1-D][1,5]BENZOTHIAZEPINES BINDING SELECTIVELY TO THE MITOCHONDRIAL BENZODIAZEPINE RECEPTOR

A series of 42 6-arylpyrrolo[2,1-d][1,5]benzothiazepines which we have recently described as selective ligands of the mitochondrial benzodia zepine receptor (MBR) (Fiorini I.; et al. J. Med. Chem. 1994, 37, 1427 -1438), have been investigated using the comparative molecular field a nalysis (CoMFA) approach. The resulting 3D-QSAR model rationalizes the steric and electronic factors which modulate affinity to the MBR with a cross-validation standard error of 0.648 pIC(50) unit. A set of sev en novel pyrrolobenzothiazepine congeners has successively been synthe sized and tested. The CoMFA model forecasts the binding affinity value s of these new compounds with a prediction standard error of 0.536.