title: A comparative molecular field analysis model for 6-arylpyrrolo[2,1-d] [1,5]benzothiazepines binding selectively to the mitochondrial benzodiazepine receptor.
abstract: A series of 42 6-arylpyrrolo[2,1-d][1,5]benzothiazepines, which we have recently described as selective ligands of the mitochondrial benzodiazepine receptor (MBR) (Fiorini I.; et al. J. Med. Chem. 1994, 37, 1427-1438), have been investigated using the comparative molecular field analysis (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 pIC50 unit. A set of seven novel pyrrolobenzothiazepine congeners has successively been synthesized and tested. The CoMFA model forecasts the binding affinity values of these new compounds with a prediction standard error of 0.536.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli, Federico II, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Greco
authors.forename: E
authors.initials: E
authors.lastname: Novellino
authors.forename: I
authors.initials: I
authors.lastname: Fiorini
authors.forename: V
authors.initials: V
authors.lastname: Nacci
authors.forename: G
authors.initials: G
authors.lastname: Campiani
authors.forename: S M
authors.initials: SM
authors.lastname: Ciani
authors.forename: A
authors.initials: A
authors.lastname: Garofalo
authors.forename: P
authors.initials: P
authors.lastname: Bernasconi
authors.forename: T
authors.initials: T
authors.lastname: Mennini
mesh_terms: D000818:Animals; D007546:Isoquinolines / Q000378:metabolism; D008024:Ligands; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D011758:Pyrroles / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D012044:Regression Analysis; D013329:Structure-Activity Relationship; D013841:Thiazepines / Q000378:metabolism*
chemical_list: D007546:Isoquinolines; D008024:Ligands; D011758:Pyrroles; D011963:Receptors, GABA-A; D013841:Thiazepines; C037850:PK 11195