Introduction：Basic information about Azilsartan kaMedoxoMil CAS 863031-24-7, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Azilsartan kaMedoxoMil Basic information
| Product Name: | Azilsartan kaMedoxoMil |
| Synonyms: | Azilsartan kaMedoxoMil;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 (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester potassium salt;Azilsartan MedoxoMil PotassiuM salt;Azilsartan MedoxoMil (MonopotassiuM salt);Azilsartan MedoxoMil (MonopotassiuM);Azilsartan MedoxiMil PotassiuM;Azilsartan KaModoxoMil;Azilsartan kaMedoxoMil (with 5 ints.) |
| CAS: | 863031-24-7 |
| MF: | C30H25KN4O8 |
| MW: | 608.65 |
| EINECS: | 1308068-626-2 |
| Product Categories: | Azilsartan Kamedoxomil;863031-24-7 |
| Mol File: | 863031-24-7.mol |
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Azilsartan kaMedoxoMil Chemical Properties
| Melting point | 193 - 195°C |
| storage temp. | Refrigerator, Under inert atmosphere |
| solubility | DMSO (Slightly), Methanol (Slightly) |
| form | Solid |
| color | White to Off-White |
| InChIKey | URRUOGRYFYNQJO-UHFFFAOYSA-N |
| SMILES | C(C1C=CC(C2C=CC=CC=2C2=NOC(=O)N2)=CC=1)N1C(=NC2=CC=CC(C(=O)OCC3=C(OC(=O)O3)C)=C12)OCC.[KH] |
Safety Information
Azilsartan kaMedoxoMil Usage And Synthesis
| Uses | Azilsartan Kamedoxomil is an angiotensin II receptor blocker. |
| Definition | ChEBI: Azilsartan kamedoxomil is an organic potassium salt that is the monopotassium salt of azilsartan medoxomil. A prodrug for azilsartan, it is used for treatment of hypertension. It has a role as a prodrug, an antihypertensive agent and an angiotensin receptor antagonist. It contains an azilsartan medoxomil(1-). |
| Clinical Use | Azilsartan kamedoxomil, developed by Takeda Pharmaceuticals,was approved for the treatment of hypertension and launched inthe U.S. under the brand name Edarbi. Edarbi is a prodrug thatundergoes rapid hydrolysis to liberate azilsartan, the active ingredient(TAK-536, 39). As the 8th angiotensin receptorblocker (ARB) to enter the world market, azilsartan kamedoxomil can function as monotherapy or in combination with other antihypertensiveagents. In several clinical studies, monotherapeutic azilsartankamedoxomil showed superior antihypertensive activity and a favorable safety/tolerability profile in patients comparedwith other established therapeutics, including valsartan, olmesartanmedoxomil, candesartan, and telmisartan.In late 2011,Takeda announced that FDA also approved the fixed-dose combinationtablet of azilsartan kamedoxomil with chlorthalidone underthe trade name of Edarbyclor. |
| Synthesis | Based on the synthesis of azilsartan, the process-scale approach to azilsartan kamedoxomil isdescribed in the scheme. The synthesis started with commerciallyavailable methyl 2-[(tert-butoxycarbonyl)amino]-3-nitrobenzoate(30), which can also be prepared by several different routes.41,42Alkylation of 30 with diaryl bromide 31 gave benzylamine 32 in78% yield, which was followed by deprotection with 30% ethanolicHCl and alkalinization to produce amine 33 in 77% yield. The nitrogroup within 33 was reduced with hydrazine hydrate and a catalyticamount of ferric chloride to afford 2,3-diaminobenzoate 34in 64% yield. Ring formation was achieved by treatment of 34 withtetraethoxymethane and acetic acid to produce benzimidazole 35in 91% yield.37 The addition of hydroxylamine to the cyano groupof 35 provided amidoxime 36 in 55% yield, which underwentimmediate cyclization upon treatment with 2-ethylhexyl chloroformate37 in refluxing xylenes to give oxadiazolone 38 in 52%yield. Hydrolysis of 38 gave azilsartan (39, TAK-536) in 94%yield. In the presence of perchlorobenzoyl chloride 40 and triethylamine,carboxylic acid 39 was converted to the mixed acidanhydride intermediate, which when condensed with alcohol 41furnished benzoate 42 in 50% yield. Salt preparation of 42 wasaccomplished with potassium 2-ethylhexyl carboxylate 43 affordingazilsartan kamedoxomil (V) in 63% yield. |
| in vivo | Azilsartan medoxomil (0.03-1 mg/kg, p.o.) monopotassium inhibits the angiotensin II-induced pressor response innormotensive rats[2].
Azilsartan medoxomil (0.1-10 mg/kg in peanut butter, once daily) monopotassium inhibits vascular wall expression of plasminogen activator inhibitor type-I (PAI-1) protein, and potentially facilitates the stabilization of atherosclerotic plaques in ApoE knockout mice on a high fat diet rendered overexpressors of PAI-1 in VSMCs[5].
Azilsartan medoxomil (0.03-10 mg/kg, oral gavage, once a day) monopotassium reduces myocardial infarct size in rats[6].
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| IC 50 | AT1 Receptor |
Azilsartan kaMedoxoMil Preparation Products And Raw materials
