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Azilsartan

Description Uses Pharmacokinetics Mechanism of Action Biological Activity Side Effects
Azilsartan
Azilsartan structure
CAS No.
147403-03-0
Chemical Name:
Azilsartan
Synonyms
CS-865;Tak 536;AZILSARTAN;AZATMint-E;Azilsartan API;Azilsartan >Unii-F9nux55p23;Azilsartan Acid;Azilsartan Base;TAK-536 fandachem
CBNumber:
CB21090899
Molecular Formula:
C25H20N4O5
Formula Weight:
456.45
MOL File:
147403-03-0.mol

Azilsartan Properties

Melting point:
188 °C(dec.)
Density 
1.42
storage temp. 
Sealed in dry,2-8°C
solubility 
DMSO: soluble15mg/mL (clear solution)
form 
powder
pka
2.05±0.10(Predicted)
color 
white to beige
InChIKey
KGSXMPPBFPAXLY-UHFFFAOYSA-N
FDA UNII
F9NUX55P23
SAFETY
  • Risk and Safety Statements
WGK Germany  3

Azilsartan price More Price(45)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich SML0432 Azilsartan ≥98% (HPLC) 147403-03-0 10mg $82.6 2021-12-16 Buy
Sigma-Aldrich SML0432 Azilsartan ≥98% (HPLC) 147403-03-0 50mg $320 2021-12-16 Buy
TCI Chemical A2601 Azilsartan >98.0%(HPLC)(T) 147403-03-0 200mg $98 2021-12-16 Buy
TCI Chemical A2601 Azilsartan >98.0%(HPLC)(T) 147403-03-0 1g $293 2021-12-16 Buy
Cayman Chemical 26091 Azilsartan 147403-03-0 100mg $89 2021-12-16 Buy

Azilsartan Chemical Properties,Uses,Production

Description

Edarbi (azilsartan medoxomil), a prodrug, is hydrolyzed to azilsartan in the gastrointestinal tract during absorption. Azilsartan is a selective AT1 subtype angiotensin II receptor antagonist. The drug substance used in the drug product formulation is the potassium salt of azilsartan medoxomil, also known by the US accepted name of azilsartan kamedoxomil and is chemically described as (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylate monopotassium salt.

Uses

Azilsartan and chlorthalidone combination is used to treat high blood pressure (hypertension). Azilsartan is an angiotensin II receptor blocker (ARB). It works by blocking a substance in the body that causes blood vessels to tighten. As a result, azilsartan relaxes the blood vessels. This lowers blood pressure and increases the supply of blood and oxygen to the heart.

Pharmacokinetics

Azilsartan differs structurally from candesartan only by replacement of candesartan’s five-membered tetrazole ring with a five-membered oxo-oxadiazole ring. Azilsartan is formulated as an ester prodrug, azilsartan medoxomil, which is rapidly hydrolysed to the bioactive molecule during gastrointestinal absorption. It produces dose-dependent reductions in vascular smooth muscle contraction, peripheral resistance, and the synthesis and effects of aldosterone on the kidneys. Azilsartan has a half-life of about 11 hours and is metabolized in the liver mainly via CYP2C9 and is eliminated in both the urine and feces.

Mechanism of Action

Edarbi, a prodrug, is hydrolyzed to azilsartan in the gastrointestinal tract during absorption. Azilsartan is a selective AT1 subtype angiotensin II receptor antagonist. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzymes (ACE, kinase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Azilsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathway for angiotensin II synthesis.

Biological Activity

Potent angiotensin II type 1 (AT1) receptor inverse agonist (IC50 = 2.6 nM at the human AT1 receptor). Inhibits angiotensin II-induced IP1 accumulation in COS-7 cells; decreases maximal contraction of rabbit aortic strips in a concentration-dependent manner (pD'2 = 9.9). Antihypertensive; prevents vascular cell proliferation and expression of PAI-1.

Side Effects

Overall, azilsartan is well-tolerated in most patients in terms of adverse effects. In a controlled, double-blind, randomized clinical trial comparing the efficacy of azilsartan medoxomil to the ACE inhibitor ramipril in 784 patients, the overall number of adverse events was reported to be much less frequent with azilsartan. During the treatment period, dizziness and hypotension occurred more often with the azilsartan treatment groups, and cough, a class side effect commonly encountered with ACE inhibitors, occurred more frequently with the ramipril group (8.2% of participants). Cough only occurred in 1% and 1.4% of azilsartan 40 and 80 mg groups, respectively. Another effect observed in the azilsartan group was a pertinent increase in serum potassium, sodium, and uric acid; no deaths resulted from this effect or the aforementioned adverse effects as well.

Description

Azilsartan is an antagonist of the angiotensin II type 1 receptor (AT1; IC50 = 0.42 μM) and the active metabolite of azilsartan medoxomil (Item No. 23805). 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.

Chemical Properties

White to Off-White Solid

Uses

Azilsartan is an analgesic and antiinflammatory drugs containing angiotensin II antagonists.

Uses

Azilsartan is an angiotensin II type 1 (AT1) receptor antagonist with IC50 of 2.6 nM

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.

Chemical Synthesis

The most likely process-scale synthetic route likely mimics that which is disclosed in Takeda’s 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.

QQ截图20210210111404.jpg

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 synthesis

147404-82-8
147403-03-0
Synthesis of Azilsartan from (Z)-Methyl 2-ethoxy-3-((2'-(N'-(ethoxycarbonyloxy)carbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d]iMidazole-4-carboxylate

Azilsartan Preparation Products And Raw materials

Raw materials

Preparation Products


Azilsartan Suppliers

Global( 364)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Shandong Hengshannuode Pharmaceutical Technology Co., Ltd.
13583348585
admin@hsnordpharma.com CHINA 92 58
Beijing Cooperate Pharmaceutical Co.,Ltd
010-60279497
010-60279497 sales01@cooperate-pharm.com CHINA 1817 55
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com China 22607 55
Jiangsu Zhongbang Pharmaceutical Co., Ltd.
025-87151996
025-87151996 zbsales@chinaredsun.com CHINA 32 55
Hangzhou FandaChem Co.,Ltd.
008615858145714
+86-571-56059825 fandachem@gmail.com CHINA 9115 55
ATK CHEMICAL COMPANY LIMITED
+86 21 5161 9050/ 5187 7795
+86 21 5161 9052/ 5187 7796 ivan@atkchemical.com CHINA 26782 60
career henan chemical co
+86-0371-55982848
sales@coreychem.com China 29954 58
HEBEI YINGONG NEW MATERIAL TECHNOLOGY CO.,LTD
+8619933070948
claire@hbyingong.com China 681 58
Hubei Jusheng Technology Co.,Ltd.
86-18871470254
027-59599243 linda@hubeijusheng.com CHINA 28229 58
Casorganics US Corp
+17326109938
sales@casorganics.com CHINA 175 58

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View Lastest Price from Azilsartan manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2022-01-06 Azilsartan
147403-03-0
US $200.00 / KG 10g 99% 500kg/month HEBEI YINGONG NEW MATERIAL TECHNOLOGY CO.,LTD
2021-11-30 Azilsartan
147403-03-0
US $1587.00 / KG 500g 99% 1000KG Baoji Guokang Bio-Technology Co., Ltd.
2021-11-27 Azilsartan
147403-03-0
US $12.00 / g 1KG 99% 5ton/Month Hebei Yirun Sega Biological Technology Co. Ltd

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