This lecture recounts the development of centrally acting 1,4-benzodiazepines, starting with Roche's mid-1950s initiative to synthesize superior tranquilizers. Using an empirical approach, researchers focused on benzheptoxdiazines (later identified as quinazoline 3-oxides). In 1957, a previously synthesized product from quinazoline N-oxide and methylamine was tested and found to have valuable pharmacological properties, leading to the discovery of chlordiazepoxide (Librium), the first 1,4-benzodiazepine. Subsequent studies yielded more potent derivatives like diazepam (Valium). Extensive structure-activity relationship research followed, with over 3000 compounds synthesized and evaluated, resulting in multiple benzodiazepine drugs marketed globally.