863031-21-4 Usage
Description
Different sources of media describe the Description of 863031-21-4 differently. You can refer to the following data:
1. Azilsartan medoxomil (Edarbi), an angiotensin II receptor antagonist,
was approved by the U.S. FDA in February 2011 for the treatment of
hypertension in adults. The discovery of azilsartan was the result
of a medicinal chemistry effort to identify an ARB with a different carboxylic
acid isostere than the ones found in the marketed ARBs. Several of the
marketed ARBs use a tetrazole group as a carboxylic acid isostere. The medicinal
chemistry approach that led to azilsartan involved the replacement of
this commonly used tetrazole with a 5-oxo-1,2,4-oxadiazole group.
Azilsartan can be synthesized by Suzuki coupling of p-tolyl boronic acid
to 2-bromobenzonitrile, followed by bromination of the methyl group.
The bromide is displaced to introduce a protected 2-ethoxy-1H-benzo[d]
imidazole-7-carboxylate. The cyano group is converted to a hydroxylamidine,
followed by reaction with an alkyl-chloroformate and intramolecular
cyclization to form the 5-oxo-1,2,4-oxadiazole ring. The acid is
then deprotected and converted to a prodrug. The parent, azilsartan has been
extensively characterized in vitro and compared with other marketed AT1
antagonists olmesartan, valsartan, telmisartan, irbesartan, and candesartan.
Azilsartan was found to be a potent (IC50=2.6 nM), selective, inverse agonist
of the AT1 receptor. From washout experiments, azilsartan was found
have slow dissociation from the receptor and thus is characterized as an insurmountable
antagonist.
2. Azilsartan medoxomil is a prodrug form of azilsartan , a potent and selective angiotensin II receptor 1 (AT1) antagonist. Azilsartan medoxomil (0.1-10 mg/kg) reduces blood pressure and decreases plasminogen activator inhibitor 1 (PAI-1) levels in the plasma, left ventricle, and aortic wall in mice in a dose-dependent manner. It also inhibits the pressor response induced by angiotensin II in normotensive rats (ID50 = 0.12 mg/kg) and reduces blood pressure and improves glucose infusion, a marker of insulin sensitivity, in spontaneously hypertensive rats. Azilsartan medoxomil also has more potent antiproteinuric effects in Wistar fatty rats than olmesartan medoxomil . Formulations containing azilsartan medoxomil have been used in the treatment of hypertension.
Originator
Takeda (United States)
Uses
Azilsartan medoxomil is a long-acting angiotensin II receptor blocker (ARB) that is used to lower hypertension. When Azilsartan medoxomil enters the gastrointestinal tract, it is rapidly converted to its active form, Azilsartan (A926900).
Definition
ChEBI: A carboxylic ester obtained by formal condensation of the carboxy group of azilsartan with the hydroxy group of 4-(hydroxymethyl)-5-methyl-1,3-dioxol-2-one. A prodrug for azilsartan, it is used for treatment of hypertension.
Brand name
Edarbi
Check Digit Verification of cas no
The CAS Registry Mumber 863031-21-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,6,3,0,3 and 1 respectively; the second part has 2 digits, 2 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 863031-21:
(8*8)+(7*6)+(6*3)+(5*0)+(4*3)+(3*1)+(2*2)+(1*1)=144
144 % 10 = 4
So 863031-21-4 is a valid CAS Registry Number.
InChI:InChI:1S/C30H24N4O8/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)
863031-21-4Relevant articles and documents
Polymorphs and solvatomorphs of azilsartan medoxomil: Elucidation of solvent-induced construction and conformational diversity
Zhang, Xian-Rui,He, Sai-Fei,Zhang, Shuo,Li, Jing,Li, Shan,Liu, Jin-Song,Zhang, Lei
, p. 103 - 113 (2017)
Two polymorphs (AM-A and AM-B) of azilsartan medoxomil (AM) and four AM solvatomorphs with toluene (AM-TOL), 1,4-dioxane (AM-DIO), chloroform (AM-TCM) and N,N-dimethylacetamide (AM-DMA) have been prepared by the hydrolysis of azilsartan medoxomil potassium in aqueous-organic solutions. In the crystal structures of two polymorphs and three solvatomorphs (AM-TOL, AM-DIO and AM-TCM), two asymmetric AM molecules form the dimeric cycle-like structures via intermolecular N[sbnd]H?N hydrogen bonds in R22 (26) ring, while AM-DMA shows intramolecular N[sbnd]H?O hydrogen bond between AM and DMA molecules. The hydrogen bonds (C[sbnd]H?O or C[sbnd]H?N) and π···π (or C[sbnd]H···π) interactions are helpful to stabilize the conformational diversity of AM. The solvent-induced experiment shows that solvent molecules have great influence on the solvatomorph formation and DIO can form the most steady solvatomorph than other solvents. The thermal study demonstrates that toluene molecules in three solvatomorphs (AM-TOL, AM-DIO and AM-TCM) are the most difficult to remove from the cage. Our results illustrate that the solvent plays significant role in tuning the size of the cage and producing the conformational diversity of AM molecules.
Preparation method of azilsartan kamedoxomil hydrate
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Paragraph 0061; 0064, (2018/09/08)
The invention provides a preparation method of azilsartan kamedoxomil hydrate. The preparation method at least comprises the following steps: (1) performing the chlorination; (2) performing the esterification; (3) forming azilsartan kamedoxomil; and (4) forming the azilsartan kamedoxomil hydrate. The preparation method has the characteristics of simple operation, high yield, high purity and good stability, and is suitable for industrialized production.
A method for preparing arab League Qi Shatan ester (by machine translation)
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Paragraph 0018 - 0021; 0046 - 0049, (2016/10/08)
The invention relates to a method of synthesizing arab League Qi Shatan ester, the method to the 4 [...] -bromo methyl-2-cyano biphenyl as the raw material and then by the hydroxylamine compound II is prepared by cyclization; to 2-ethoxylbenzimidazole-7-carboxylic acid as raw materials to carry out the esterification reaction to make compound V, then utilize the compound prepared with compound II arab League Qi Shatan ester V reaction. The method of the present invention the synthetic route is short, the operation is simple, high yield, at the same time reduces the raw material 4 the [...] -bromomethyl-2-cyanobiphenyl consumption, the cost is reduced. (by machine translation)