Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Alniditan: Difference between pages

{{Short description|Chemical compound}}

| Verifiedfields = changed

| verifiedrevid = 477318521

| routes_of_administration =

| excretion =

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 152317-89-0

| IUPHAR_ligand = 120

| index2_label = Dihydrochloride

| CAS_number2_Ref = {{cascite|correct|CAS}}

| CAS_number2 = 155428-00-5

| UNII2_Ref = {{fdacite|correct|FDA}}

| UNII2 = 54PE58MGKB

'''Alniditan''' is a [[5-HT1D receptor|5-HT_1D receptor]] [[agonist]] with [[migraine]]-preventive effects.<ref name="pmid8967979">{{cite journal | vauthors = Leysen JE, Gommeren W, Heylen L, Luyten WH, Van de Weyer I, Vanhoenacker P, Haegeman G, Schotte A, Van Gompel P, Wouters R, Lesage AS | display-authors = 6 | title = Alniditan, a new 5-hydroxytryptamine1D agonist and migraine-abortive agent: ligand-binding properties of human 5-hydroxytryptamine1D alpha, human 5-hydroxytryptamine1D beta, and calf 5-hydroxytryptamine1D receptors investigated with [3H]5-hydroxytryptamine and [3H]alniditan | journal = Molecular Pharmacology | volume = 50 | issue = 6 | pages = 1567–1580 | date = December 1996 | pmid = 8967979 }}</ref>

==Synthesis==

The sizeable number of serotonergic drugs for treating migraines all incorporate the indole nucleus found in serotonin itself. It is thus of interest that a compound based on a [[benzopyran]] manifests much the same activity.

[[File:Alniditan synthesis.svg|thumb|center|400px|Alniditan synthesis:<ref>{{Cite journal | doi = 10.1016/0960-894X(95)00473-7 | title = The discovery of a series of new non-indole 5HT1D agonists | year = 1995 | vauthors = Van Lommen G, De Bruyn M, Schroven M, Verschueren W, Janssens W, Verrelst J, Leysen J | journal = Bioorganic & Medicinal Chemistry Letters | volume = 5 | issue = 22 | pages = 2649–2654 }}</ref>]]

Alkylation of [[phenol]] with 2-bromobutyrolactone ('''2''') leads to the ether ('''3'''). Oxidation of that product with [[chromium trioxide]] then leads to the substituted [[succinic anhydride]] ('''4'''). Treatment of anhydride with [[polyphosphoric acid]] leads to

the [[acylation]] of the aromatic ring and the formation of the [[benzopyranone]] ring ('''5'''). The [[ketone]] is then selectively reduced by any of several methods, as, for example, conversion to a [[dithiolane]] followed by [[Mozingo reduction]] to '''6'''. The [[carboxylic acid]] is next reduced to the corresponding [[aldehyde]] ('''7''') by successive conversion to an [[acid chloride]] followed by [[hydrogenation]] in the presence of [[thiophene]]. A second [[hydrogenation]] in the presence of [[benzylamine]] leads to the [[reductive amination]] product ('''8'''). [[Michael addition]] of the amino group in '''8''' to [[acrylonitrile]] leads to a [[1,4-addition]] and the formation of ('''9'''). Reduction of the [[nitrile]] affords the [[diamine]] ('''10'''). Reaction of this last diamine with [[tetrahydropyrimidine chloride]] ('''11'''), itself formed by treatment of [[trimethylene urea]] with [[phosphorus oxychloride]], leads to the displacement of halogen by the terminal, and thus more accessible, amino group in ('''10'''). There is thus formed the serotonergic agent alniditan ('''12''').

== References ==

{{Reflist}}

{{Antimigraine}}

{{Serotonergics}}

[[Category:Antimigraine drugs]]

[[Category:Benzopyrans]]

[[Category:5-HT1D agonists]]

{{Analgesic-stub}}