Synthesis of pyrido[2,3-d]pyridazines and pyrazino[2,3-d]-pyridazines—novel classes of GABAA receptor benzodiazepine binding site ligands

Novel syntheses of 2,3,8-trisubstituted pyrido2,3-d]pyridazines and 2,3,5-trisubstituted pyrazino2,3-d]pyridazines are described. Two complementary routes to pyrido2,3-d]pyridazines were developed, the first of which began by constructing the pyridine ring, and the second of which started by constructing the pyridazine ring. Pyrazino2,3-d]pyridazines were prepared in a route employing an aza-Wadsworth-Emmons cyclization as the key step. The resulting compounds were found to be high affinity ligands for the GABA_A receptor benzodiazepine binding site.