Azilsartan kaMedoxoMil Chemische Eigenschaften,Einsatz,Produktion Methoden

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 in the U.S. under the brand name Edarbi. Edarbi is a prodrug that undergoes rapid hydrolysis to liberate azilsartan, the active ingredient (TAK-536, 39). As the 8th angiotensin receptor blocker (ARB) to enter the world market, azilsartan kamedoxomil can function as monotherapy or in combination with other antihypertensive agents. In several clinical studies, monotherapeutic azilsartan kamedoxomil showed superior antihypertensive activity and a favorable safety/tolerability profile in patients compared with other established therapeutics, including valsartan, olmesartan medoxomil, candesartan, and telmisartan.In late 2011,Takeda announced that FDA also approved the fixed-dose combination tablet of azilsartan kamedoxomil with chlorthalidone under the trade name of Edarbyclor.

Synthese

Based on the synthesis of azilsartan, the process-scale approach to azilsartan kamedoxomil is described in the scheme. The synthesis started with commercially available methyl 2-[(tert-butoxycarbonyl)amino]-3-nitrobenzoate (30), which can also be prepared by several different routes.41,42 Alkylation of 30 with diaryl bromide 31 gave benzylamine 32 in 78% yield, which was followed by deprotection with 30% ethanolic HCl and alkalinization to produce amine 33 in 77% yield. The nitro group within 33 was reduced with hydrazine hydrate and a catalytic amount of ferric chloride to afford 2,3-diaminobenzoate 34 in 64% yield. Ring formation was achieved by treatment of 34 with tetraethoxymethane and acetic acid to produce benzimidazole 35 in 91% yield.37 The addition of hydroxylamine to the cyano group of 35 provided amidoxime 36 in 55% yield, which underwent immediate cyclization upon treatment with 2-ethylhexyl chloroformate 37 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 acid anhydride intermediate, which when condensed with alcohol 41 furnished benzoate 42 in 50% yield. Salt preparation of 42 was accomplished with potassium 2-ethylhexyl carboxylate 43 affording azilsartan kamedoxomil (V) in 63% yield.

Azilsartan kaMedoxoMil Upstream-Materialien And Downstream Produkte

Upstream-Materialien

Downstream Produkte

Azilsartan kaMedoxoMil Anbieter Lieferant Produzent Hersteller Vertrieb H?ndler.

Firmenname	Telefon	E-Mail	Land	Produktkatalog	Edge Rate
Xuchang Hengsheng Pharmaceutical Co., Ltd	+86-03745692999 +86-13569491380	xccxn@xchsyy.com	China	15	58
Henan Tianfu Chemical Co.,Ltd.	+86-0371-55170693 +86-19937530512	info@tianfuchem.com	China	21634	55
career henan chemical co	+86-0371-86658258 +8613203830695	sales@coreychem.com	China	29884	58
Shenzhen Nexconn Pharmatechs Ltd	+86-755-89396905 +86-15013857715	admin@nexconn.com	China	10310	58
HubeiwidelychemicaltechnologyCo.,Ltd	18627774460	faith@widelychemical.com	CHINA	742	58
Chongqing Chemdad Co., Ltd	+86-023-6139-8061 +86-86-13650506873	sales@chemdad.com	China	39894	58
Zhengzhou Alfa Chemical Co.,Ltd	+8618530059196	sale04@alfachem.cn	China	13507	58
SIMAGCHEM CORP	+86-13806087780	sale@simagchem.com	China	17365	58
AFINE CHEMICALS LIMITED	+86-0571-85134551	sales@afinechem.com	China	15354	58
Finetech Industry Limited	+86-27-87465837 +8618971612321	info@finetechnology-ind.com	China	9640	58

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• 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.)
• Azilsartan MedoxMil PotassuiM
• 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-, (5-Methyl-2-oxo-1,3-dioxol-4-yl)Methyl ester, potassiuM salt
• Azilsartan Medoxomil Potassium
• Azilsartan Mehtyl ester
• Azilsartan Impurity 50 Potassium Salt
• Azilsartan medoxomil monopotassium (TAK 491)
• Azilsartan KaMedoximil
• Azilsartan Medoxomil Potassium Crude
• Azilsartan Impurity 45 Potassium Salt
• (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)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate, potassium salt
• TAK 491 kamedoxomil
• TAK-491 monopotassium
• Azilsartan Impurity 60 Potassium Salt
• (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)-[1,1'-biphenyl]-4-yl)methyl)-1H-benzo[d]imidazole-7-carboxylate, potassium salt
• Potassium 3-(4'-((2-ethoxy-7-(((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)carbonyl)-1H-benzo[d]imidazol-1-yl)methyl)-[1,1'-biphenyl]-2-yl)-5-oxo-5H-1,2,4-oxadiazol-2-ide
• AZILSARTAN KAMEDOXOMIL IH
• 863031-24-7
• C30H23KN4O8
• C30H23N4O8K
• Azilsartan Kamedoxomil
• 863031-24-7