Astemizol

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H315：Verursacht Hautreizungen.

  H319：Verursacht schwere Augenreizung.

  H335：Kann die Atemwege reizen.

• Sicherheit

  P261：Einatmen von Staub vermeiden.

  P264：Nach Gebrauch gründlich waschen.

  P264：Nach Gebrauch gründlich waschen.

  P271：Nur im Freien oder in gut belüfteten Räumen verwenden.

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

  P302+P352：BEI BERÜHRUNG MIT DER HAUT: Mit viel Wasser/... (Hersteller kann, falls zweckmäßig, ein Reinigungsmittel angeben oder, wenn Wasser eindeutig ungeeignet ist, ein alternatives Mittel empfehlen) waschen.

  P305+P351+P338：BEI KONTAKT MIT DEN AUGEN: Einige Minuten lang behutsam mit Wasser spülen. Eventuell vorhandene Kontaktlinsen nach Möglichkeit entfernen. Weiter spülen.

Astemizole Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R22:Gesundheitsschädlich beim Verschlucken.
  R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.

• S-Sätze Betriebsanweisung:

  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
  S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.

• Beschreibung

  Astemizole belongs to the second-generation class of non-sedating, non-anticholinergic antihistamines. Its non-sedating properties appear to result from its poor penetration of the blood brain barrier. As a result it shows no potentiation of CNS depressants, including alcohol. Its long half-life allows once-daily dosing.

• Chemische Eigenschaften

  Crystalline Solid

• Originator

  Janssen (Belgium)

• Verwenden

  Astemizole is used for preventing and treating severe seasonal and chronic allergic rhinitis, allergic conjunctivitis, hives, Quinke’s edema, other allergic conditions and dermatitis. Synonyms of this drug are hismanal, histazol, and others.

• Verwenden

  scabicide

• Verwenden

  Nonsedating-type histamine H1-receptor antagonist. Potential for combination therapy with antivancer drugs such as doxorubicin in resistant leukemia. Antihistaminic

• Definition

  ChEBI: A piperidine compound having a 2-(4-methoxyphenyl)ethyl group at the 1-position and an N-[(4-fluorobenzyl)benzimidazol-2-yl]amino group at the 4-position.

• Manufacturing Process

  A mixture of 2.3 parts of 2-(4-methoxyphenyl)ethyl methanesulfonate, 4.9 parts of 1-[(4-fluorophenyl)methyl]-N-(4-piperidinyl)-1H-benzimidazol-2- amine dihydrobromide, 3.2 parts of sodium carbonate, 0.1 part of potassium iodide and 90 parts of N,N-dimethylformamide is stirred overnight at 70°C. The reaction mixture is poured onto water. The product is extracted with methylbenzene. The extract is washed with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from 2,2'-oxybispropane, yielding 2.2 parts (48%) of 1- (4-fluorophenylmethyl)-N-[1-[2-(4-methoxyphenyl)ethyl]-4-piperidinyl]-1Hbenzimidazol- 2-amine, MP 149.1°C.

• Trademarks

  Hismanal (Janssen);Alermizol;Astezol;Astol;Histamanal;Novo-nastizol;EISMANAL.

• Therapeutic Function

  Antiallergic, Antihistaminic

• Weltgesundheitsorganisation (WHO)

  The first clinically interesting histamine ti-antagonists were introduced in the late forties and early fifties. Several histamine ti-antagonists have a similar cardiac effect to that seen with astemizole and terfenadine. Serious cardiovascular adverse reactions have been reported when used concomitantly with imidazole antifungals and macrolide antibiotics.

• Biologische Aktivität

  Orally active, potent histamine H 1 antagonist (IC 50 = 4 nM) that displays 20-fold, > 250-fold and > 250-fold selectivity over 5-HT, dopamine and muscarinic acetylcholine receptors respectively. Exhibits antimalarial activity in multidrug resistant strains in vitro (IC 50 = 227 - 734 nM). Also potent hERG K + channel blocker (IC 50 = 0.9 nM) that displays cardiotoxicity in vivo .

• Biochem/physiol Actions

  Astermizole is a potent hERG potassium channel blocker (IC50 of 0.9 nM) and may used as a pharmacological chaperone to correct folding defects and restore protein function for some mutated forms of hERG channels. It has also been studied for treatment of malaria, hERG and hEAG channel function in cancer and as a second generation antihistamine H-1 antagonist.

• Sicherheitsprofil

  Poison by subcutaneous andintravenous routes. Moderately toxic by ingestion. Humansystemic effects by ingestion: arrhythmias, coma, nauseaor vomiting, somnolence. When heated to decompositionit emits toxic fumes of F?? and NOx.

• Synthese

  Astemizole, 1-[(4-fluorophenyl)methyl]-N-[1-[2-(4-methoxyphenyl) ethyl]-4- piperidinyl]-benzimidazol-2-amine (16.1.31), is synthesized in a multi-stage synthesis from 1-carbethoxy-4-aminopiperidine and 2-nitroisothiocyanobenzol, from which a derivative of thiourea (16.1.26) is synthesized upon their reaction. The nitro group of the product is reduced and the further S-methoxided. In reaction conditions intermolecular cyclization into a derivative of benimidazol, N-[1-[2-(4-carethoxy)]-4-piperidinyl]benzimidazol-2-amine (16.1.28) occurs. The obtained aminobenzimidazole derivative is alkylated with 4-fluorobenzylchoride into 1-[(flurophenyl)methyl]-N-[1-[2-(4-carethoxy)]-4-piperidinyl] benzimidazol- 2-amine (16.1.29). The carbethoxyl group of the resulting compound (16.1.29) is hydrolyzed by hydrobromic acid, forming a non-substituted on the nitrogen atom derivative of piperidine (16.1.30), the alkylation of which with 2-(4-methoxyphenyl)ethylmetanesulfonate leads to the formation of astemizole (16.1.31).

  

• Lager

  Store at +4°C

• Einzelnachweise

  1) Richards et al. (1984), Astemizole. A review of its pharmacodynamic properties and therapeutic efficacy; Drugs, 28 38 2) Laduron et al. (1982), In vitro and in vivo binding characteristics of a new long-acting histamine H1 antagonist, astemizole; Mol. Pharmacol., 21 294

Astemizole Upstream-Materialien And Downstream Produkte

Astemizol Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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