Azilsartan

Base Information

• Chemical Name: Azilsartan
• CAS No.: 147403-03-0
• Molecular Formula: C25H20N4O5
• Molecular Weight: 456.458
• Mol file: 147403-03-0.mol

Synonyms:see 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-;TAK 536;2-Ethoxy-1-[[2'-(4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid;

Chemical Property of Azilsartan

Chemical Property:

• Melting Point: 188 °C(dec.)
• PKA: 2.05±0.10(Predicted)
• PSA: 123.24000
• Density: 1.42 cm³
• LogP: 4.19180
• Storage Temp.: 2-8°C
• Solubility.: DMSO: soluble15mg/mL (clear solution)

Purity/Quality:

99%, ^*data from raw suppliers

Azilsartan ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• 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. 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.
• 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. Azilsartan is an analgesic and antiinflammatory drugs containing angiotensin II antagonists. Azilsartan is an angiotensin II type 1 (AT1) receptor antagonist with IC50 of 2.6 nM
• 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.

Technology Process of Azilsartan

There total 49 articles about Azilsartan which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.5%

ethyl ester of 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 (1403474-70-3) → azilsartan (147403-03-0)

Guidance literature:

With water; sodium hydroxide; at 50 ℃; for 4h;

Reference yield: 97.1%

C25H19N4O5(1-)*Na(1+) → azilsartan (147403-03-0)

Guidance literature:

With citric acid; In water; at 5 ℃; pH=5; Reagent/catalyst;

Reference yield: 96.8%

methyl 2-ethoxy-1-((2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1H-benzo[d]-imidazole-7-carboxylate (147403-52-9) → azilsartan (147403-03-0)

Guidance literature:

methyl 2-ethoxy-1-((2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1H-benzo[d]-imidazole-7-carboxylate; With water; sodium hydroxide; In methanol; at 20 ℃; for 24h;

With hydrogenchloride; In water; Product distribution / selectivity;

upstream raw materials:

methyl 2-ethoxy-1-((2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl)methyl)-1H-benzo[d]-imidazole-7-carboxylate

methyl 1-[(2'-cyanobiphenyl-4-yl)methyl]-2-ethoxy-benzimidazole-7-carboxylate

methyl 2-ethoxy-1-((2′-(N′-hydroxycarbamimidoyl)-biphenyl-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate

pyrographite

Downstream raw materials:

Azilsartan medoxomil

(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-oxo-3-((2’-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1’-biphenyl]-4-yl)methyl)-2,3-dihydro-1H-benzo[d]imidazole-4-carboxylate

(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-ethoxy-1-((2′-(4-ethyl-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-biphenyl-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate

(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester of 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 dimethylacetamide

Refernces

• 1、 Chapala, Vijaya Lakshmi,Katari, Naresh Kumar,Malavattu, Giri Prasad,Marisetti, Vishnu Murthy,Jonnalagadda, Sreekantha B.. "An Improved Preparation of Azilsartan". . p. 550 - 555. Retrieved 2020.
• 2、 -. "Synthesis technology for continuously preparing azilsartan in micro-channel reactor". Paragraph 0060-0067. . Retrieved 2020/02/19.