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The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and was made available in 1960 by Hoffmann–La Roche, which followed with the development of diazepam (Valium) three years later, in 1963. [1]
Chlordiazepoxide (initially called methaminodiazepoxide) was the first benzodiazepine to be synthesized in the mid-1950s. The synthesis was derived from work on a class of dyes, quinazoline-3-oxides. [33] It was discovered by accident when in 1957 tests revealed that the compound had hypnotic, anxiolytic, and muscle relaxant effects.
Librium, based on the R0 6-690 compound discovered by Sternbach in 1956, was approved for use in 1960. In 1963, its improved version, Valium, was released and became astonishingly popular: between 1969 and 1982, it was the most prescribed drug in America, with over 2.3 billion doses sold in its peak year of 1978.
The first tricyclic antidepressant (TCA), imipramine was discovered. 1958. Aaron B. Lerner et al. of Yale University isolated the hormone melatonin, which was found to regulate the circadian rhythm. 1960s. Aaron T. Beck developed cognitive therapy. 1960. The first benzodiazepine, chlordiazepoxide, under the trade name Librium was introduced. 1961
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In 1833 French chemist Anselme Payen was the first to discover an enzyme, diastase. In 1834, François Mothes and Joseph Dublanc created a method to produce a single-piece gelatin capsule that was sealed with a drop of gelatin solution. In 1853 Alexander Wood was the first physician that used hypodermic needle to dispense drugs via Injections.
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The structure that the first benzodiazepine is based on was discovered by Leo H. Sternbach. He thought the compound had a heptoxdiazine structure (Figure 7) but it was later determined to be a quinazoline-3-oxide. Possible drug candidates were then synthesized from that compound and screened for activity.