Azilsartan medoxomil | TAK-491 | CAS#863031-21-4 | angiotensin II receptor type 1 antagonist

MedKoo Cat#: 319902 | Name: Azilsartan medoxomil

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Azilsartan medoxomil also known as TAK-491, is an orally administered angiotensin II receptor type 1 antagonist (blocker) used in the treatment of adults with essential hypertension. Azilsartan medoxomil is a useful and attractive new option for lowering BP in patients with essential hypertension, particularly for those not able to tolerate other antihypertensive drugs. Further studies are required to evaluate the effects of azilsartan medoxomil on cardiovascular morbidity and mortality.

Chemical Structure

Azilsartan medoxomil

CAS#863031-21-4 (free acid)

Theoretical Analysis

MedKoo Cat#: 319902

Name: Azilsartan medoxomil

CAS#: 863031-21-4 (free acid)

Chemical Formula: C30H24N4O8

Exact Mass: 568.1594

Molecular Weight: 568.54

Elemental Analysis: C, 63.38; H, 4.26; N, 9.85; O, 22.51

Price and Availability

Size	Price	Availability
100mg	USD 90.00	Ready to ship
250mg	USD 180.00	Ready to ship
500mg	USD 285.00	Ready to ship
1g	USD 450.00	Ready to ship
2g	USD 750.00	Ready to ship
5g	USD 1,650.00	2 Weeks
10g	USD 2,950.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

863031-24-7 (potassium) 863031-21-4 (free acid)

Synonym

TAK-491; TAK 491; TAK491; Azilsartan medoxomil; Azilsartan medoxomil potassium; trade name: Edarbi. Ipreziv.

IUPAC/Chemical Name

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

InChi Key

QJFSABGVXDWMIW-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

O=C(C1=C2C(N=C(OCC)N2CC3=CC=C(C4=CC=CC=C4C5=NC(ON5)=O)C=C3)=CC=C1)OCC6=C(C)OC(O6)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C23B03B16

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Azilsartan medoxomil(TAK 491) is an orally administered angiotensin II receptor type 1 antagonist with IC50 of 0.62 nM.

In vitro activity:

The results in Figure 2A–C demonstrate that while exposure to AGEs significantly increased the expression levels of IL-1α, IL-6, and TNF-β roughly to 3.1 ± 0.34, 3.6 ± 0.4, and 4.3 ± 0.46-fold. However, 10 µM Azilsartan inhibited the mRNA expression of these three cytokines to 2.2 ± 0.24, 2.6 ± 0.28, and 3.1 ± 0.33-fold. Furthermore, 20 µM Azilsartan inhibited them to 1.7 ± 0.2, 1.9 ± 0.22, and 2.4 ± 0.27-fold. A similar inhibitory effect was observed on the protein secretion of these three cytokines, suggesting a distinct anti-inflammatory effect of Azilsartan in OA chondrocytes (Figure 2D–F). Reference: J Biochem Mol Toxicol. 2021 May 29:e22827. https://pubmed.ncbi.nlm.nih.gov/34051020/

In vivo activity:

Azilsartan treatment resulted in a dose-dependent reduction of systolic arterial blood pressure in both experimental age groups. The TBARS levels decreased significantly in the high-dose azilsartan treatment group at later stages of MetS. Reference: Cardiovasc Drugs Ther. 2019 Oct;33(5):501-509. https://pubmed.ncbi.nlm.nih.gov/31420755/

	Solvent	mg/mL	mM
Solubility
	DMSO	119.5	210.19

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 568.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Lei J, He M, Xu L, He C, Li J, Wang W. Azilsartan prevented AGE-induced inflammatory response and degradation of aggrecan in human chondrocytes through inhibition of Sox4. J Biochem Mol Toxicol. 2021 May 29:e22827. doi: 10.1002/jbt.22827. Epub ahead of print. PMID: 34051020. 2. Li W, Wang C, Zhang D, Zeng K, Xiao S, Chen F, Luo J. Azilsartan ameliorates ox-LDL-induced endothelial dysfunction via promoting the expression of KLF2. Aging (Albany NY). 2021 May 4;13(9):12996-13005. doi: 10.18632/aging.202973. Epub 2021 May 4. PMID: 33946046; PMCID: PMC8148451. 3. Han J, Tang H, Yao L, Jin E, Pan W, Chen S. Azilsartan protects against hyperglycemia-induced hyperpermeability of the blood-brain barrier. Bioengineered. 2021 Dec;12(1):3621-3633. doi: 10.1080/21655979.2021.1948950. PMID: 34266350. 4. Kagota S, Maruyama-Fumoto K, Shimari M, McGuire JJ, Shinozuka K. Angiotensin II Type 1 Receptor Antagonist Azilsartan Restores Vascular Reactivity Through a Perivascular Adipose Tissue-Independent Mechanism in Rats with Metabolic Syndrome. Cardiovasc Drugs Ther. 2019 Oct;33(5):501-509. doi: 10.1007/s10557-019-06900-1. PMID: 31420755.

In vitro protocol:

In vivo protocol:

1. Han J, Tang H, Yao L, Jin E, Pan W, Chen S. Azilsartan protects against hyperglycemia-induced hyperpermeability of the blood-brain barrier. Bioengineered. 2021 Dec;12(1):3621-3633. doi: 10.1080/21655979.2021.1948950. PMID: 34266350. 2. Kagota S, Maruyama-Fumoto K, Shimari M, McGuire JJ, Shinozuka K. Angiotensin II Type 1 Receptor Antagonist Azilsartan Restores Vascular Reactivity Through a Perivascular Adipose Tissue-Independent Mechanism in Rats with Metabolic Syndrome. Cardiovasc Drugs Ther. 2019 Oct;33(5):501-509. doi: 10.1007/s10557-019-06900-1. PMID: 31420755.

1: Handley A, Lloyd E, Roberts A, Barger B. Safety and tolerability of azilsartan medoxomil in subjects with essential hypertension: a one-year, phase 3, open-label study. Clin Exp Hypertens. 2016;38(2):180-8. doi: 10.3109/10641963.2015.1081213. Epub 2016 Jan 28. PubMed PMID: 26817604. 2: White WB, Cuadra RH, Lloyd E, Bakris GL, Kupfer S. Effects of azilsartan medoxomil compared with olmesartan and valsartan on ambulatory and clinic blood pressure in patients with type 2 diabetes and prediabetes. J Hypertens. 2016 Jan 12. [Epub ahead of print] PubMed PMID: 26766564. 3: Webb NJ, Wells T, Tsai M, Zhao Z, Juhasz A, Dudkowski C. Single-dose pharmacokinetics and safety of azilsartan medoxomil in children and adolescents with hypertension as compared to healthy adults. Eur J Clin Pharmacol. 2016 Jan 4. [Epub ahead of print] PubMed PMID: 26725367. 4: Bramlage P, Schmieder RE, Gitt AK, Baumgart P, Mahfoud F, Buhck H, Ouarrak T, Ehmen M, Potthoff SA; EARLY Registry Group. The renin-angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril in clinical trials versus routine practice: insights from the prospective EARLY registry. Trials. 2015 Dec 19;16:581. doi: 10.1186/s13063-015-1100-8. PubMed PMID: 26686682; PubMed Central PMCID: PMC4684935. 5: Tsai MC, Wu J, Kupfer S, Vakilynejad M. Population Pharmacokinetics and Exposure-Response of a Fixed-Dose Combination of Azilsartan Medoxomil and Chlorthalidone in Patients with Stage 2 Hypertension. J Clin Pharmacol. 2015 Dec 3. doi: 10.1002/jcph.684. [Epub ahead of print] PubMed PMID: 26632101. 6: Harrell RE, Karim A, Zhang W, Dudkowski C. Effects of Age, Sex, and Race on the Safety and Pharmacokinetics of Single and Multiple Doses of Azilsartan Medoxomil in Healthy Subjects. Clin Pharmacokinet. 2015 Oct 27. [Epub ahead of print] PubMed PMID: 26507722. 7: Kuze Y, Kogame A, Jinno F, Kondo T, Asahi S. Development, validation and application of the liquid chromatography tandem mass spectrometry method for simultaneous quantification of azilsartan medoxomil (TAK-491), azilsartan (TAK-536), and its 2 metabolites in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Sep 15;1001:174-81. doi: 10.1016/j.jchromb.2015.07.047. Epub 2015 Jul 30. PubMed PMID: 26279009. 8: Swain D, Patel PN, Palaniappan I, Sahu G, Samanthula G. Liquid chromatography/tandem mass spectrometry study of forced degradation of azilsartan medoxomil potassium. Rapid Commun Mass Spectrom. 2015 Aug 15;29(15):1437-47. doi: 10.1002/rcm.7235. PubMed PMID: 26147484. 9: Schmieder RE, Potthoff SA, Bramlage P, Baumgart P, Mahfoud F, Buhck H, Ouarrak T, Ehmen M, Senges J, Gitt AK; EARLY Registry Group. Patients With Newly Diagnosed Hypertension Treated With the Renin Angiotensin Receptor Blocker Azilsartan Medoxomil vs Angiotensin-Converting Enzyme Inhibitors: The Prospective EARLY Registry. J Clin Hypertens (Greenwich). 2015 Dec;17(12):947-53. doi: 10.1111/jch.12603. Epub 2015 Jun 24. PubMed PMID: 26105590. 10: Kipnes MS, Handley A, Lloyd E, Barger B, Roberts A. Safety, tolerability, and efficacy of azilsartan medoxomil with or without chlorthalidone during and after 8 months of treatment for hypertension. J Clin Hypertens (Greenwich). 2015 Mar;17(3):183-92. doi: 10.1111/jch.12474. Epub 2015 Jan 24. PubMed PMID: 25619410. 11: Ebeid WM, Elkady EF, El-Zaher AA, El-Bagary RI, Patonay G. Stability-indicating RP-LC method for determination of azilsartan medoxomil and chlorthalidone in pharmaceutical dosage forms: application to degradation kinetics. Anal Bioanal Chem. 2014 Oct;406(26):6701-12. doi: 10.1007/s00216-014-8085-0. Epub 2014 Sep 5. PubMed PMID: 25190009. 12: Abdelsaid M, Coucha M, Ergul A. Cerebrovasculoprotective effects of azilsartan medoxomil in diabetes. Transl Res. 2014 Nov;164(5):424-32. doi: 10.1016/j.trsl.2014.06.003. Epub 2014 Jun 17. PubMed PMID: 24999268; PubMed Central PMCID: PMC4250409. 13: Baker WL, Nigro SC, White WB. Efficacy of azilsartan medoxomil with chlorthalidone in hypertension. Expert Rev Cardiovasc Ther. 2014 Jul;12(7):791-8. doi: 10.1586/14779072.2014.924853. Epub 2014 Jun 2. Review. PubMed PMID: 24881461. 14: Ebeid WM, Elkady EF, El-Zaher AA, El-Bagary RI, Patonay G. Spectrophotometric and spectrofluorimetric studies on azilsartan medoxomil and chlorthalidone to be utilized in their determination in pharmaceuticals. Anal Chem Insights. 2014 May 7;9:33-40. doi: 10.4137/ACI.S13768. eCollection 2014. PubMed PMID: 24855334; PubMed Central PMCID: PMC4022702. 15: Weber MA, White WB, Sica D, Bakris GL, Cao C, Roberts A, Kupfer S. Effects of combining azilsartan medoxomil with amlodipine in patients with stage 2 hypertension. Blood Press Monit. 2014 Apr;19(2):90-7. doi: 10.1097/MBP.0000000000000027. PubMed PMID: 24445723; PubMed Central PMCID: PMC3966914. 16: Barrios V, Escobar C. Azilsartan medoxomil in the treatment of hypertension: the definitive angiotensin receptor blocker? Expert Opin Pharmacother. 2013 Nov;14(16):2249-61. doi: 10.1517/14656566.2013.834887. Epub 2013 Sep 26. Review. PubMed PMID: 24070321. 17: Lastra G, Santos FR, Hooshmand P, Hooshmand P, Mugerfeld I, Aroor AR, Demarco VG, Sowers JR, Henriksen EJ. The Novel Angiotensin II Receptor Blocker Azilsartan Medoxomil Ameliorates Insulin Resistance Induced by Chronic Angiotensin II Treatment in Rat Skeletal Muscle. Cardiorenal Med. 2013 Jul;3(2):154-164. Epub 2013 Jun 25. PubMed PMID: 23922555; PubMed Central PMCID: PMC3721134. 18: Pierini D, Anderson KV. Azilsartan medoxomil/chlorthalidone: a new fixed-dose combination antihypertensive. Ann Pharmacother. 2013 May;47(5):694-703. doi: 10.1345/aph.1R618. Epub 2013 Apr 12. PubMed PMID: 23585646. 19: Preston RA, Karim A, Dudkowski C, Zhao Z, Garg D, Lenz O, Sica DA. Single-center evaluation of the single-dose pharmacokinetics of the angiotensin II receptor antagonist azilsartan medoxomil in renal impairment. Clin Pharmacokinet. 2013 May;52(5):347-58. doi: 10.1007/s40262-013-0044-y. PubMed PMID: 23575872. 20: Bönner G, Bakris GL, Sica D, Weber MA, White WB, Perez A, Cao C, Handley A, Kupfer S. Antihypertensive efficacy of the angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril. J Hum Hypertens. 2013 Aug;27(8):479-86. doi: 10.1038/jhh.2013.6. Epub 2013 Mar 21. PubMed PMID: 23514842; PubMed Central PMCID: PMC3715765.