863031-24-7

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 NO: 863031-24-7
• Molecular Formula: C30H23N4O8.K
• Molecular Weight: 607.63200
• EINECS: 1308068-626-2
• Product Categories: Azilsartan Kamedoxomil
• Mol File: 863031-24-7.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• Storage Temp.: Refrigerator, Under inert atmosphere
• Solubility: DMSO (Slightly), Methanol (Slightly)
• CAS DataBase Reference: Azilsartan kaMedoxoMil(CAS DataBase Reference)
• NIST Chemistry Reference: Azilsartan kaMedoxoMil(863031-24-7)
• EPA Substance Registry System: Azilsartan kaMedoxoMil(863031-24-7)

Safety Data

• Hazardous Substances Data: 863031-24-7(Hazardous Substances Data)

Usage

Uses

Azilsartan Kamedoxomil is an angiotensin II receptor blocker.

Definition

ChEBI: An organic potassium salt that is the monopotassium salt of azilsartan medoxomil. A prodrug for azilsartan, it is used for treatment of hypertension.

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.

Synthesis

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.

InChI:InChI:1S/C30H24N4O8.K/c1-3-38-28-31-23-10-6-9-22(27(35)39-16-24-17(2)40-30(37)41-24)25(23)34(28)15-18-11-13-19(14-12-18)20-7-4-5-8-21(20)26-32-29(36)42-33-26;/h4-14H,3,15-16H2,1-2H3,(H,32,33,36);/q;+1/p-1