Mining the Chemical Abstracts database with pharmacophore-based queries

A method is described to convert 3D patterns of pharmacophoric groups into 2D queries for molecular substructure searches of the Chemical Abstracts database with SciFinder Scholar ®. The results of such searches and the options for refinement of the hit lists are presented using a rigid tetrahydroisoquinoline-carbazole (IQC) hybrid molecule fitted onto previously developed pharmacophores for subtype-selective α 1-adrenergic receptor antagonists as an example. The compounds retrieved were further analysed by limiting their physical properties to ‘drug-like’ ranges and by enumerating the ring skeletons they contain. Selected ring skeletons were evaluated by fitting them on to the original pharmacophores. Several structurally novel rigid ring skeletons were found with this new database mining technique which are potentially useful as leads in the design of α 1B selective adrenergic receptor antagonists.