Imidazo[1,2-b]pyridazines: Synthesis and interaction with central and peripheral-type (mitochondrial) benzodiazepine receptors

The fundamental chemistry of pyridazines, the syntheses of substituted imidazo[1,2-b]pyridazines (1) (and some related compounds) and the interaction of the products with central benzodiazepine receptors (CBR) and peripheral-type (mitochondrial) benzodiazepine receptors (PBR) are described. Some of these imidazo[1,2-b]pyridazines had high selective affinity for the central benzodiazepine receptors and others had high selectivity for the peripheral-type (mitochondrial) benzodiazepine receptors. The results of structure-activity studies and molecular modeling will be reported. In vivo tests of some compounds which interacted strongly with the central benzodiazepine receptors revealed reasonably potent anticonvulsant/anticonflict activity, and some of those which bind selectively to the peripheral type (mitochondrial) benzodiazepine receptors are being examined as possible radiopharmaceuticals for imaging of tumors (and other disease states).