Chemical compound
Pharmaceutical compound
Piperoxan , also known as benodaine , was the first antihistamine to be discovered.[ 1] [ 2] benzodioxan , was prepared in the early 1930s by Daniel Bovet and Ernest Fourneau at the Pasteur Institute in France .[ 1] [ 2] 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] Nobel Prize in Physiology or Medicine for his contribution.[ 4] Anne-Marie Staub , published the first structure–activity relationship (SAR) study of antihistamines in 1939.[ 1] 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
Synthesis:[ 6] [ 7] 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
^ a b c d Scriabine A, Landau R, Achilladelis B (1999). "Discovery and Development of Major Drugs" . Pharmaceutical innovation: revolutionizing human health . Philadelphia: Chemical Heritage Press. ISBN 0-941901-21-1 ^ a b c Nelson WL (2008). "Antihistamines and Related Antiallergic and Antiulcer Agents" . In Williams DH, Lemke TL, Foye WO (eds.). Foye's Principles of Medicinal Chemistry . Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 978-0-7817-6879-5 ^ Fourneau E, Bovet D (1933). "Recherches sur l'action sympathicolytique d'un nouveau dérivé du dioxane". Archives Internationales de Pharmacodynamie et de Thérapie . 46 : 178– 91. ISSN 0003-9780 . ^ "Daniel Bovet" . Biography . NobelPrize.org.^ Landau R, Achilladelis B, Scriabine A (1999). "Discovery and Development of Major Drugs" . Pharmaceutical Innovation: Revolutionizing Human Health . Chemical Heritage Foundation. pp. 230–. ISBN 978-0-941901-21-5 ^ Nelson WL, Wennerstrom JE, Dyer DC, Engel JE (July 1977). "Absolute configuration of glycerol derivatives. 4. Synthesis and pharmacological activity of chiral 2-alkylaminomethylbenzodioxans, competitive alpha-adrenergic antagonists". Journal of Medicinal Chemistry . 20 (7): 880– 885. doi :10.1021/jm00217a002 . eISSN 1520-4804 . PMID 17749 . ^ US 2056046 , Fourneau E, "Manufacture of bases derived from benz-dioxane", issued 29 September 1936, assigned to Rhone Poulenc SA
α1
Agonists Antagonists
Abanoquil Ajmalicine Alfuzosin Anisodamine Anisodine Atiprosin Atypical antipsychotics (e.g., brexpiprazole , clozapine , olanzapine , quetiapine , risperidone )Benoxathian Beta blockers (e.g., adimolol , amosulalol , arotinolol , carvedilol , eugenodilol , labetalol )Buflomedil Bunazosin Corynanthine Dapiprazole Domesticine Doxazosin Ergolines (e.g., acetergamine , ergotamine , dihydroergotamine , lisuride , nicergoline , terguride )Etoperidone Fenspiride Hydroxyzine Indoramin Ketanserin L-765,314 mCPP Mepiprazole Metazosin Monatepil Moxisylyte Naftopidil Nantenine Neldazosin Niaprazine Niguldipine Pardoprunox Pelanserin Perlapine Phendioxan Phenoxybenzamine Phentolamine Phenylpiperazine antidepressants (e.g., hydroxynefazodone , nefazodone , trazodone , triazoledione )Piperoxan Prazosin Quinazosin Quinidine Silodosin Spegatrine Spiperone Talipexole Tamsulosin Terazosin Tiodazosin Tolazoline Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin )Tricyclic antidepressants (e.g., amitriptyline , clomipramine , doxepin , imipramine , trimipramine )Trimazosin Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine )Urapidil WB-4101 Zolertine
α2
Agonists Antagonists
1-PP Adimolol Amesergide Aptazapine Atipamezole Atypical antipsychotics (e.g., asenapine , brexpiprazole , clozapine , lurasidone , olanzapine , paliperidone , quetiapine , risperidone , zotepine )Azapirones (e.g., buspirone , gepirone , ipsapirone , tandospirone )BRL-44408 Buflomedil Cirazoline Efaroxan Esmirtazapine Fenmetozole Fluparoxan Idazoxan Ketanserin Lisuride mCPP Mianserin Mirtazapine NAN-190 Pardoprunox Phentolamine Phenoxybenzamine Piperoxan Piribedil Rauwolscine Rotigotine Setiptiline Spegatrine Spiroxatrine Sunepitron Terguride Tolazoline Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine )Yohimbine
β
H1
Agonists Antagonists
Others: Atypical antipsychotics (e.g., aripiprazole , asenapine , brexpiprazole , brilaroxazine , clozapine , iloperidone , olanzapine , paliperidone , quetiapine , risperidone , ziprasidone , zotepine )Phenylpiperazine antidepressants (e.g., hydroxynefazodone , nefazodone , trazodone , triazoledione )Tetracyclic antidepressants (e.g., amoxapine , loxapine , maprotiline , mianserin , mirtazapine , oxaprotiline )Tricyclic antidepressants (e.g., amitriptyline , butriptyline , clomipramine , desipramine , dosulepin (dothiepin) , doxepin , imipramine , iprindole , lofepramine , nortriptyline , protriptyline , trimipramine )Typical antipsychotics (e.g., chlorpromazine , flupenthixol , fluphenazine , loxapine , perphenazine , prochlorperazine , thioridazine , thiothixene )
H2
H3
H4
