Piperoxan
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| Clinical data | |
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| Other names | Benodaine |
| Routes of administration | Oral |
| ATC code |
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Piperoxan, also known as benodaine, was the first
α-adrenergic-blocking agent, they demonstrated that it also antagonized histamine-induced bronchospasm in guinea pigs, and published their findings in 1933.[1][2][3] Bovet went on to win the 1957 Nobel Prize in Physiology or Medicine for his contribution.[4] One of Bovet and Fourneau's students, Anne-Marie Staub, published the first structure–activity relationship (SAR) study of antihistamines in 1939.[1] Piperoxan and analogues themselves were not clinically useful due to the production of toxic effects in humans and were followed by phenbenzamine (Antergan) in the early 1940s, which was the first antihistamine to be marketed for medical use.[5]
Synthesis
Condensation of catechol [120-80-9] (1) with epichlorohydrin 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 with thionyl chloride gives 2-chloromethyl-1,4-benzodioxane [2164-33-2] (4). Displacement of the leaving group by piperidine completed the synthesis of piperoxan (5).
References
- ^ ISBN 0-941901-21-1.
- ^ ISBN 978-0-7817-6879-5.
- ISSN 0003-9780.
- ^ "Daniel Bovet". Biography. NobelPrize.org.
- ISBN 978-0-941901-21-5.
- PMID 17749.
- ^ US 2056046, Fourneau E, "Manufacture of bases derived from benz-dioxane", issued 29 September 1936, assigned to Rhone Poulenc SA