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| Other names | Benodaine |
| Routes of administration | Oral |
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| Formula | C14H19NO2 |
| Molar mass | 233.311 g·mol−1 |
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Piperoxan, also known asbenodaine, was the firstantihistamine to be discovered.[1][2] This compound, derived frombenzodioxan, was prepared in the early 1930s byDaniel Bovet andErnest Fourneau at thePasteur Institute inFrance.[1][2] Formerly investigated by Fourneau as anα-adrenergic-blocking agent, they demonstrated that it alsoantagonizedhistamine-inducedbronchospasm inguinea pigs, and published their findings in 1933.[1][2][3] Bovet went on to win the 1957Nobel Prize in Physiology or Medicine for his contribution.[4] One of Bovet and Fourneau's students,Anne-Marie Staub, published the firststructure–activity relationship (SAR) study of antihistamines in 1939.[1] Piperoxan andanalogues themselves were not clinically useful due to the production oftoxic effects in humans and were followed byphenbenzamine (Antergan) in the early 1940s, which was the first antihistamine to be marketed for medical use.[5]
Condensation ofcatechol [120-80-9] (1) withepichlorohydrin in the presence of an aqueous base can be visualized as proceeding initially with the epoxide (2) Opening of the oxirane ring by the phenoxide anion then leads to 2-hydroxymethyl-1,4-benzodioxane [3663-82-9] (3). Halogenation withthionyl chloride gives 2-chloromethyl-1,4-benzodioxane [2164-33-2] (4). Displacement of the leaving group by piperidine completed the synthesis of piperoxan (5).
