Azilsartan medoxomil
[CAS 863031-21-4]

Identification

• Classification: Biochemical >> Inhibitor >> Endocrinology & hormones >> RAAS antagonist
• Name: Azilsartan medoxomil
• Synonyms: TAK 491; 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
• Molecular Formula: C₃₀H₂₄N₄O₈
• Molecular Weight: 568.53
• CAS Registry Number: 863031-21-4
• SMILES: CCOC1=NC2=CC=CC(=C2N1CC3=CC=C(C=C3)C4=CC=CC=C4C5=NOC(=O)N5)C(=O)OCC6=C(OC(=O)O6)C

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Boiling point: 748.0±70.0 °C 760 mmHg (Calc.)^*
• Flash point: 406.2±35.7 °C (Calc.)^*
• Solubility: DMSO: 114 mg/mL, Water: <1 mg/mL, Ethanol: <1 mg/mL (Expl.)
• Index of refraction: 1.68 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

chemBlink Chemical Story

Azilsartan medoxomil, CAS 863031-21-4, is an orally administered prodrug of azilsartan and an angiotensin II receptor blocker developed by Takeda. PubChem records the formula C30H24N4O8 and the development code TAK-491. The medoxomil group masks the carboxylic acid of azilsartan as an ester, improving the properties needed for oral delivery; after administration, ester hydrolysis converts the prodrug to active azilsartan.

Azilsartan belongs to the angiotensin receptor blocker, or ARB, class. Angiotensin II normally activates the AT1 receptor, promoting vasoconstriction and other responses that raise blood pressure. Active azilsartan selectively antagonizes this receptor and reduces angiotensin II signaling. The medoxomil portion is not the long-term active pharmacophore; its job is to deliver azilsartan efficiently and then be removed metabolically.

The molecule grew from Takeda's research on benzimidazole-based angiotensin II receptor antagonists. A distinguishing structural feature of azilsartan is its 5-oxo-1,2,4-oxadiazole ring, used in place of the tetrazole group found in several earlier ARBs. Medicinal-chemistry optimization produced azilsartan and then the medoxomil ester TAK-491 as the orally suitable prodrug.

The U.S. FDA approved azilsartan medoxomil as Edarbi on February 25, 2011, for treatment of hypertension in adults. The FDA label identifies it as an angiotensin II receptor blocker and notes that it can be used alone or with other antihypertensive agents. The distinction between CAS 863031-21-4 and azilsartan itself is important: this CAS refers to the medoxomil prodrug, not simply to the active hydrolysis product.

Azilsartan medoxomil illustrates a central principle of prodrug design. Sometimes the molecule with the desired receptor activity is not the molecular form best suited for administration. Medicinal chemists can temporarily mask a polar functional group, use the modified molecule to improve delivery, and rely on metabolism to reveal the active drug after absorption.

References:
1. PubChem, Azilsartan medoxomil, CID 135409642, CAS 863031-21-4.
2. U.S. FDA, Edarbi (azilsartan medoxomil) Prescribing Information, initial U.S. approval 2011.
3. Takeda Pharmaceutical Company, Edarbi U.S. availability announcement, April 15, 2011.

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