Azilsartan free acid TAK-536 | CAS#147403-03-0 | angiotensin II receptor antagonist

MedKoo Cat#: 319526 | Name: Azilsartan free acid

Description:

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

Azilsartan is an angiotensin II receptor antagonist used in the treatment of hypertension, developed by Takeda. It is marketed in tablet form under the trade name Edarbi as the prodrug azilsartan medoxomil (INN, codenamed TAK-491). Azilsartan medoxomil lowers blood pressure by blocking the action of angiotensin II, a vasopressor hormone.

Chemical Structure

Azilsartan free acid

CAS#147403-03-0 (free acid)

Theoretical Analysis

MedKoo Cat#: 319526

Name: Azilsartan free acid

CAS#: 147403-03-0 (free acid)

Chemical Formula: C25H20N4O5

Exact Mass: 456.1434

Molecular Weight: 456.46

Elemental Analysis: C, 65.78; H, 4.42; N, 12.27; O, 17.53

Price and Availability

Size	Price	Availability
2g	USD 250.00	2 weeks
5g	USD 550.00	2 weeks
10g	USD 950.00	2 weeks
50g	USD 1,950.00	2 weeks
100g	USD 2,950.00	2 weeks

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Related CAS #

1824707-75-6 (trimethylethanolamine) 147403-03-0 (free acid) 1346599-45-8 (deuterated forms d5)

Synonym

TAK-536; TAK-536; TAK-536; Azilsartan; Azilsartan free base

IUPAC/Chemical Name

2-Ethoxy-1-[[2'-(4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]benzimidazole-7-carboxylic acid

InChi Key

KGSXMPPBFPAXLY-UHFFFAOYSA-N

InChi Code

InChI=1S/C25H20N4O5/c1-2-33-24-26-20-9-5-8-19(23(30)31)21(20)29(24)14-15-10-12-16(13-11-15)17-6-3-4-7-18(17)22-27-25(32)34-28-22/h3-13H,2,14H2,1H3,(H,30,31)(H,27,28,32)

SMILES Code

O=C(C1=C2C(N=C(OCC)N2CC(C=C3)=CC=C3C4=CC=CC=C4C5=NOC(N5)=O)=CC=C1)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

Instruction

View handling instruction

Biological target:

Azilsartan(TAK-536) is a specific and potent angiotensin II type 1 receptor antagonist with IC50 of 2.6 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	41.2	90.17
	DMF	5.0	10.95
	DMF:PBS (pH 7.2) (1:1)	0.5	23.99
	Ethanol	0.1	0.22

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 456.46 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: Naruse M, Koike Y, Kamei N, Sakamoto R, Yambe Y, Arimitsu M. Effects of azilsartan compared with telmisartan on insulin resistance in patients with essential hypertension and type 2 diabetes mellitus: An open-label, randomized clinical trial. PLoS One. 2019 Apr 3;14(4):e0214727. doi: 10.1371/journal.pone.0214727. eCollection 2019. PubMed PMID: 30943275; PubMed Central PMCID: PMC6447197. 2: Fukuda M, Isobe-Sasaki Y, Sato R, Miura T, Mizuno M, Ono M, Kiyono K, Yamamoto Y, Hayano J, Ohte N. The angiotensin II type 1 receptor blocker azilsartan can overwhelm the sympathetic nerve activation stimulated by coadministration of calcium channel blockers. J Renin Angiotensin Aldosterone Syst. 2019 Jan-Mar;20(1):1470320319839525. doi: 10.1177/1470320319839525. PubMed PMID: 30915878; PubMed Central PMCID: PMC6437324. 3: Li N, Fan L, Wu B, Dai G, Jiang C, Guo Y, Wang D. Preparation and in vitro/in vivo evaluation of azilsartan osmotic pump tablets based on the preformulation investigation. Drug Dev Ind Pharm. 2019 Mar 25:1-10. doi: 10.1080/03639045.2019.1593441. [Epub ahead of print] PubMed PMID: 30909753. 4: Hardin MD, Jacobs TF. Azilsartan. 2019 Mar 31. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK538473/ PubMed PMID: 30860708. 5: Ehlken B, Shlaen M, Lopez Fuensalida de Torres MDP, Hisada M, Bennett D. Use of azilsartan medoxomil in the primary-care setting in Germany: A real-world evidence study. Int J Clin Pharmacol Ther. 2019 Mar 8. doi: 10.5414/CP203359. [Epub ahead of print] PubMed PMID: 30848243. 6: Miyoshi T, Onoue G, Ito H. Effect of Switching to Azilsartan From Fixed-Dose Combination of an Angiotensin II Receptor Blocker and Calcium Channel Blocker or a Thiazide in Patients With Hypertension. J Clin Med Res. 2019 Mar;11(3):202-207. doi: 10.14740/jocmr3723. Epub 2019 Feb 13. PubMed PMID: 30834043; PubMed Central PMCID: PMC6396784. 7: He Y, Zhang W, Guo T, Zhang G, Qin W, Zhang L, Wang C, Zhu W, Yang M, Hu X, Singh V, Wu L, Gref R, Zhang J. Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan. Acta Pharm Sin B. 2019 Jan;9(1):97-106. doi: 10.1016/j.apsb.2018.09.003. Epub 2018 Sep 7. PubMed PMID: 30766781; PubMed Central PMCID: PMC6361728. 8: Matsuo Y, Suematsu Y, Tomita S, Tashiro K, Kuwano T, Kitajima K, Miura SI. Unique mode of binding between angiotensin II type 1 receptor and its blockers. Clin Exp Hypertens. 2018 Nov 19:1-6. doi: 10.1080/10641963.2018.1545851. [Epub ahead of print] PubMed PMID: 30453795. 9: Hussein LA, Magdy NN, Ibrahim MA. Stability-Indicating RP-UPLC Method for Simultaneous Determination of Azilsartan Medoxomil and Chlorthalidone in Tablets in the Presence of Its Degradation Products. J Chromatogr Sci. 2019 Mar 1;57(3):213-219. doi: 10.1093/chromsci/bmy102. PubMed PMID: 30395199. 10: Li Y, Zhu H, Yang J, Ke K, Zhu Y, Chen L, Qu Y, Suo R, Chen X, Zhu Y. Discovering Proangiogenic Drugs in Ischemic Stroke Based on the Relationship between Protein Domain and Drug Substructure. ACS Chem Neurosci. 2019 Jan 16;10(1):507-517. doi: 10.1021/acschemneuro.8b00381. Epub 2018 Oct 29. PubMed PMID: 30346717. 11: Collier DJ, Juhasz A, Agabiti-Rosei E, Lloyd E, Hisada M, Zhao L, Kupfer S, Caulfield MJ. Efficacy and safety of azilsartan medoxomil/chlortalidone fixed-dose combination in hypertensive patients uncontrolled on azilsartan medoxomil alone: A randomized trial. J Clin Hypertens (Greenwich). 2018 Oct;20(10):1473-1484. doi: 10.1111/jch.13376. Epub 2018 Oct 9. PubMed PMID: 30302936. 12: Ferdinand KC, Bakris GL, Cushman WC, Weber MA, Lloyd E, Wu J, White WB. Comparison of Effectiveness of Azilsartan Medoxomil and Olmesartan in Blacks Versus Whites With Systemic Hypertension. Am J Cardiol. 2018 Nov 1;122(9):1496-1505. doi: 10.1016/j.amjcard.2018.07.022. Epub 2018 Aug 4. PubMed PMID: 30217371. 13: Komaki H, Iwasa M, Hayakawa Y, Okamoto C, Minatoguchi S, Yamada Y, Kanamori H, Kawasaki M, Nishigaki K, Minatoguchi S. Azilsartan attenuates cardiac damage caused by high salt intake through the downregulation of the cardiac (pro)renin receptor and its downstream signals in spontaneously hypertensive rats. Hypertens Res. 2018 Nov;41(11):886-896. doi: 10.1038/s41440-018-0099-0. Epub 2018 Sep 12. PubMed PMID: 30209283. 14: Weber MA, Sever P, Juhasz A, Roberts A, Cao C. A randomized trial of the efficacy and safety of azilsartan medoxomil combined with chlorthalidone. J Renin Angiotensin Aldosterone Syst. 2018 Jul-Sep;19(3):1470320318795000. doi: 10.1177/1470320318795000. PubMed PMID: 30175930; PubMed Central PMCID: PMC6122257. 15: Mishra S, Ingole S, Jain R. Salt sensitivity and its implication in clinical practice. Indian Heart J. 2018 Jul - Aug;70(4):556-564. doi: 10.1016/j.ihj.2017.10.006. Epub 2017 Oct 10. Review. PubMed PMID: 30170653; PubMed Central PMCID: PMC6116721. 16: Grigoreva NY, Koroleva ME. [Choice of an Optimal Blocker of the Renin-Angiotensin-Aldosterone System in Patients With Concomitant Arterial Hypertension and Chronic Obstructive Pulmonary Disease]. Kardiologiia. 2018 Aug;(8):50-57. Russian. PubMed PMID: 30131042. 17: Mahmood NMA, Hussain SA, Mirza RR. Azilsartan improves the effects of etanercept in patients with active rheumatoid arthritis: a pilot study. Ther Clin Risk Manag. 2018 Aug 7;14:1379-1385. doi: 10.2147/TCRM.S174693. eCollection 2018. PubMed PMID: 30122937; PubMed Central PMCID: PMC6086094. 18: Liu SJ, Liu XY, Li JH, Guo J, Li F, Gui Y, Li XH, Yang L, Wu CY, Yuan Y, Li JJ. Gastrodin attenuates microglia activation through renin-angiotensin system and Sirtuin3 pathway. Neurochem Int. 2018 Nov;120:49-63. doi: 10.1016/j.neuint.2018.07.012. Epub 2018 Jul 31. PubMed PMID: 30075231. 19: Enya K, Saji BT, Kato T, Okamoto H, Koumura E. Pharmacokinetics of a Single Dose of Azilsartan in Pediatric Patients: A Phase 3, Open-Label, Multicenter Study. Adv Ther. 2018 Aug;35(8):1181-1190. doi: 10.1007/s12325-018-0754-5. Epub 2018 Jul 19. PubMed PMID: 30027478; PubMed Central PMCID: PMC6096965. 20: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK501769/ PubMed PMID: 30000828.