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Leo Sternbach was born in Abbazia, Croatia, in 1907. He studied pharmacy and organic chemistry at Jagellonian University in Cracow, Poland, and as a postgraduate student synthesized several heptoxdiazine compounds. After a short academic career, Sternbach, joined Hoffmann-La Roche, one of the major Swiss pharmaceutical companies in Basel, moved in 1941 from Switzerland to the United States, and some years later became Director of Medicinal Chemistry at Roche’s research facility in Nutley, New Jersey.

In 1954, while searching for drugs with psychotropic properties, he returned to his early interest as a postgraduate student, and synthesized a series of heptoxdiazines which, at the time, he recognized were quinazoline-3-oxides, and treated one of them with methylamine. From the reaction resulted 2-methylamino-7-chloro-5-phenyl-3H-1, 4-benzodiazepine 4-oxide, a substituted 1,4 benzodiazepine, that was  given the generic name, methaminodiazepoxide first and chlordiazepoxide subsequently, in 1957, pharmacologic screening revealed that the substance had similar pharmacologic profile to meprobamate, a widely used drug for relieving anxiety and tension at the time. In 1960, chlordiazepoxide, the first benzodiazepine compound was introduced into clinical use as an anxiolytic with the brand name of Librium. From the several other “benzodiazepines” Sternbach synthesized, diazepam was introduced also primarily for treatment of anxiety; flurazepam, nitrazepam, and flunitrazepam for insomnia; and clonazepam for epilepsy. During the 1960s chlordiazepoxide and especially diazepam became widely used substances around the world; from 1969 to 1982, diazepam was the most prescribed drugs in the United States. They were instrumental in opening up research in the neuropsychopharmacology of anxiety. Sternbach died in 2005 at age 98.

Sternbach LH. 1,4 – Benzodiazepines: chemistry and some aspects of the structure-activity relationship.  Agnew Chem 1971; 10: 34-43. Sternbach LH. The discovery of Librium. Agents and Actions 1972; 2 193-6.

Thomas A. Ban

June 13, 2013