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Azilsartan

Azilsartan Structure
Azilsartan structure
CAS No.
147403-03-0
Chemical Name:
Azilsartan
Synonyms
Azilsartan Base;2-Ethoxy-1-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid;Azilsartan Acid;CS-865;Tak 536;Azisartan;AZILSARTAN;AZATMint-E;Azilsartan API;Azilsartan >
CBNumber:
CB21090899
Molecular Formula:
C25H20N4O5
Molecular Weight:
456.45
MDL Number:
MFCD20278186
MOL File:
147403-03-0.mol
MSDS File:
SDS
Last updated:2024-04-25 17:59:01
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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

Symbol(GHS)  GHS hazard pictograms
GHS08
Signal word  Warning
Hazard statements  H361-H413
Precautionary statements  P501-P273-P202-P201-P280-P308+P313-P405
WGK Germany  3
HS Code  2934.99.4400

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 $98.5 2024-03-01 Buy
Sigma-Aldrich SML0432 Azilsartan ≥98% (HPLC) 147403-03-0 50mg $382 2024-03-01 Buy
TCI Chemical A2601 Azilsartan >98.0%(HPLC)(T) 147403-03-0 200mg $115 2024-03-01 Buy
TCI Chemical A2601 Azilsartan >98.0%(HPLC)(T) 147403-03-0 1g $345 2024-03-01 Buy
Cayman Chemical 26091 Azilsartan 147403-03-0 100mg $110 2024-03-01 Buy
Product number Packaging Price Buy
SML0432 10mg $98.5 Buy
SML0432 50mg $382 Buy
A2601 200mg $115 Buy
A2601 1g $345 Buy
26091 100mg $110 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 . 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 angiotensin II type 1 (AT1) receptor antagonist with IC50 of 2.6 nM

Uses

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.

Synthesis

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.
Synthesis_147403-03-0
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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

1403474-70-3
147403-03-0
Synthesis of Azilsartan from 1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, ethyl ester

Azilsartan Preparation Products And Raw materials

Raw materials

1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, Methyl ester

Preparation Products

(Z)-Methyl 2-ethoxy-3-((2'-(N'-hydroxycarbaMiMidoyl)biphenyl-4-yl)Methyl)-3H-benzo[d] iMidazole-4-carboxylate

Azilsartan Suppliers

Global( 541)Suppliers
Supplier Tel Email Country ProdList Advantage
Changzhou Rokechem Technology Co., Ltd.
18758118018 sales001@rokechem.com China 255 58
Sinoway Industrial co., ltd. 		0592-5800732; +8613806035118 xie@china-sinoway.com China 992 58
Hangzhou ICH Biofarm Co., Ltd 		+undefined8613073685410 sales@ichemie.com China 985 58
Shanghai Affida new material science and technology center 		+undefined15081010295 2691956269@qq.com China 359 58
Ouhuang Engineering Materials (Hubei) Co., Ltd 		+8617702722807 admin@hbouhuang.com China 2259 58
Capot Chemical Co.,Ltd. 		571-85586718 +8613336195806 sales@capotchem.com China 29797 60
Beijing Cooperate Pharmaceutical Co.,Ltd 		010-60279497 sales01@cooperate-pharm.com CHINA 1811 55
Henan Tianfu Chemical Co.,Ltd. 		+86-0371-55170693 +86-19937530512 info@tianfuchem.com China 21691 55
Jiangsu Zhongbang Pharmaceutical Co., Ltd. 		025-87151996 zbsales@chinaredsun.com CHINA 32 55
Hangzhou FandaChem Co.,Ltd. 		008657128800458; +8615858145714 fandachem@gmail.com China 9348 55
Supplier Advantage
Changzhou Rokechem Technology Co., Ltd.
58
Sinoway Industrial co., ltd. 		58
Hangzhou ICH Biofarm Co., Ltd 		58
Shanghai Affida new material science and technology center 		58
Ouhuang Engineering Materials (Hubei) Co., Ltd 		58
Capot Chemical Co.,Ltd. 		60
Beijing Cooperate Pharmaceutical Co.,Ltd 		55
Henan Tianfu Chemical Co.,Ltd. 		55
Jiangsu Zhongbang Pharmaceutical Co., Ltd. 		55
Hangzhou FandaChem Co.,Ltd. 		55

Related articles

  • Synthesis of Azilsartan
  • Azilsartan (Azilsartan), the trade name is Azilva,It was approved to be marketed in Japan on January 18, 2012. It has now been....
  • Sep 16，2021

View Lastest Price from Azilsartan manufacturers

Image Update time Product Price Min. Order Purity Supply Ability Manufacturer
Azilsartan pictures 2024-04-25 Azilsartan
147403-03-0
 US $0.00-0.00 / KG 1KG 99 50000KG/month Shanghai Affida new material science and technology center
Azilsartan pictures 2024-04-24 Azilsartan
147403-03-0
 US $0.00-0.00 / mg 10mg 0.98 10g ShenZhen H&D Pharmaceutical Technology Co., LTD
Azilsartan pictures 2024-04-24 Azilsartan
147403-03-0
 US $201.00 / kg 1kg 99.9% 200000kg Ouhuang Engineering Materials (Hubei) Co., Ltd
  • Azilsartan pictures
  • Azilsartan
    147403-03-0
  • US $0.00-0.00 / KG
  • 99
  • Shanghai Affida new material science and technology center
  • Azilsartan pictures
  • Azilsartan
    147403-03-0
  • US $0.00-0.00 / mg
  • 0.98
  • ShenZhen H&D Pharmaceutical Technology Co., LTD
  • Azilsartan pictures
  • Azilsartan
    147403-03-0
  • US $201.00 / kg
  • 99.9%
  • Ouhuang Engineering Materials (Hubei) Co., Ltd

Azilsartan Spectrum

Azilsartan(147403-03-0)1HNMR

147403-03-0(Azilsartan)Related Search:

Thiophanate-methyl Tribenuron methyl Methyl salicylate Biphenyl Kresoxim-methyl
Bifonazole Aspartame Tolvaptan 1H-BenziMidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl] -2-ethoxy-, ethyl ester O-Desethyl Azilsartan
ethyl2-oxo-3-((2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)Methyl)-2,3-dihydro-1H-benzo[d]iMidazole-4-carboxylate Azilsartan Medoxomil 4-(Hydroxymethyl)-5-methyl-1,3-dioxol-2-one Methyl 1H-BENZOIMIDAZOLE-4-CARBOXYLIC ACID
N-Hydroxyacetamidine BENZAMIDOXIME HYDROCHLORIDE Methyl bromide

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AZILSARTAN 2-Ethoxy-1-[[2'-(4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid Azilsartan 2-ethoxy -1- {[2'-(5-oxo-4,5-dihydro -1,2,4 -oxadiazol-3-yl) biphenyl-4-yl ] methyl} -1H –benzimi[d]dazole-7-carboxylic acid 2-ethoxy-1-((2'-(5-oxo-4,5-dihydro- 1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylic acid 2-Ethoxy-1-[[2'-(4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid Tak 536 Unii-F9nux55p23 2-ethoxy-3-((2'-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)Methyl)-3H-benzo[d]iMidazole-4-carboxylic acid Azilsartan 2-Ethoxy-1-[[2'-(4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]Methyl]benziMidazole-7-carboxylic acid 1-[[2'-(2,5-Dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]Methyl]-2-ethoxy-1H-benziMidazole-7-carboxylic Acid Azilsartan (TAK-536) AzilsartanMedoxoMilInterMediates-3 2. 2-Ethoxy-1-[[2'-(4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]Methyl]benziMidazole-7-carboxylic acid 2-Ethoxy-1-｛[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl) biphenyl-4-yl]Methyl ｝-1H-benzo -[d]iMidazole-7- carboxylic acid 1H-Benzimidazole-7-carboxylic acid, 1-[[2'-(2,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)[1,1'-biphenyl]-4-yl]methyl]-2-ethoxy- Azilsartan metabolite MI D4 Azilsartan metabolite MII-D4 Azilsartan API AZATMint-E Azilsartan, ≥98% (HPLC) CS-865 Azilsartan > 2-Ethoxy-1-[(2-5-Oxo-4,5-Dihydro-1,2,4-Oxadiazol-3-Yl)Biphenyl-4-Yl] Methyl-1H-Benzimidazole-7-Carboxalic Biphenyl-4-Yl] Methyl-1H-Benzimidazole-7-Carboxalic Acid Azilsartan USP/EP/BP 1-[2’-(4,5-dihydro-5-oxo-4H-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]-2-ethoxy-1-H-benzimidazole-7- carboxylic acid 2-Ethoxy-1-[(2-5-Oxo-4,5-Dihydro-1,2,4-Oxadiazol-3-Yl) Biphenyl-4-Yl] Methyl-1H-Benzimidazole-7-Carboxalic Acid Generic API Azilsartan 2-Ethoxy-1-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid Azilsartan Acid Azilsartan Base 2-Ethoxy-1-((2'-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylic acid 2-Ethoxy-1-[[2’-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic Acid Azilsartan 1-[[2’-(2,5-Dihydro-5-oxo-1,2,4-oxadiazol-3-yl) [1,1’-biphenyl]-4-yl]methyl]-2-ethoxy-1H-benzimidazole-7- carboxylic Acid Azisartan 2-Ethoxy-1-((2'-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylic acid 147403-03-0 Intermediates Aromatics Heterocycles Intermediates & Fine Chemicals Pharmaceuticals 147403-03-0