Azilsartan

Bezeichnung:Azilsartan

CAS-Nr147403-03-0

Englisch Name:Azilsartan

CBNumberCB21090899

SummenformelC25H20N4O5

Molgewicht456.45

MOL-Datei147403-03-0.mol

Azilsartan physikalisch-chemischer Eigenschaften

Schmelzpunkt	188 °C(dec.)
Dichte	1.42
storage temp.	Sealed in dry,2-8°C
Löslichkeit	DMSO: soluble15mg/mL (clear solution)
Aggregatzustand	powder
pka	2.05±0.10(Predicted)
Farbe	white to beige
InChIKey	KGSXMPPBFPAXLY-UHFFFAOYSA-N

Sicherheit

WGK Germany	3
HS Code	2934.99.4400
Giftige Stoffe Daten	147403-03-0(Hazardous Substances Data)

Gefahreninformationscode (GHS)

Azilsartan Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Azilsartan is an antagonist of the angiotensin II type 1 receptor (AT₁; IC₅₀ = 0.42 μM) and the active metabolite of azilsartan medoxomil . Azilsartan is formed from azilsartan medoxomil by hydrolysis in the gastrointestinal tract and liver. Azilsartan also acts as an inverse agonist, inhibiting angiotensin II-induced accumulation of inositol-1-phosphate in COS-7 cells expressing recombinant human AT₁ (IC₅₀ = 2.6 nM). It reduces the maximal contractile response induced by angiotensin II in isolated rabbit aortic strips (pD₂ = 9.9). Azilsartan (100 ng/kg, i.v.) inhibits the angiotensin II-induced pressor response in conscious normotensive rats.
Chemische Eigenschaften
White to Off-White Solid
Verwenden
Azilsartan is an angiotensin II type 1 (AT1) receptor antagonist with IC50 of 2.6 nM
Verwenden
Azilsartan is an analgesic and antiinflammatory drugs containing angiotensin II antagonists.
Definition
ChEBI: A benzimidazolecarboxylic acid that is benzimidazole-7-carboxylic acid substituted at position 2 by a methoxy group and at position 1 by a 2'-[(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl group. Used (as the prodrug, azilsartan medoxomil) f r treatment of hypertension.
Clinical Use
Azilsartan is an orally active angiotensin II blocker which was approved and launched in Japan for the treatment of arterial hypertension in May 2012. Azilsartan, which is marketed under the trade name Azilva®, was discovered and developed by Takeda—the same firm which had developed and launched a prodrug of azilsartan (azilsartan kamedoxomil, Edarbi®) in 2010. Azilsartan exhibits higher potency and slower off-rate kinetics for type 1 angiotensin II receptors, which contributes to azilsartan’s comparatively improved blood pressure lowering effect.
Synthese
The most likely process-scale synthetic route likely mimics that which is disclosed in Takeda?ˉs patents, and this is described in the scheme below. Commercial available benzoic acid 21 was activated as the correspndong acyl azide and underwent a Curtius rearrangement to give carbamate 22 in 57% yield (three steps from compound 21). The resulting aniline 22 was then alkylated with commercial 4- (bromomethyl)-2'-cyanobiphenyl 23 to give benzylamine 24 in 85% yield. Nitroamine 24 was then exposed to mildly acidic conditions to affect Boc-removal prior to reduction via ferric chloride hydrate in the presence of hydrazine hydrate. The resulting diamine 25 arose in 64% yield across the two-step sequence. Interestingly, tt was found that metal catalysts under conventional hydrogenation conditions caused partial debenzylation, which led the authors to arrive at the hydrazine/ferric chloride conditions. Next, benzimidazole formation was achieved upon treatment of diamine 25 with ethyl orthocarbonate in acetic acid. The resulting ethoxylbenzimidazole 26 was procured in 86% yield, and this benzonitrile was further reacted with hydroxylamine hydrochloride and sodium methoxide to provide amidoxime 27 in 90% as white powder. Next, activation with ethyl chlorocarbonate gave 28 followed by heating in refluxing xylene to give oxadiazolone 29 in 23% yield from hydroxyamidine 27. Finally ester 29 was saponified with 2N LiOH in methanol to give azilsartan (V) in 84% yield.

An improved scalable route (Scheme below) to azilsartan was reported and features reproducibly better yields.43 Hydroxyamidine 30 was treated with dimethyl carbonate and sodium methoxide, which triggered they key cyclization along with concomitant transesterification to deliver 29. Milder aqueous sodium hydroxide hydrolysis converted this methyl ester 29 to azilsartan (V) in 88-90% yield.

Azilsartan Upstream-Materialien And Downstream Produkte

Azilsartan Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

147403-03-0, Azilsartan Verwandte Suche:

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