| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
As a prodrug form, the target of olmesartan ethyl ester‘s active metabolite olmesartan is the angiotensin II type 1 receptor (AT1R). Olmesartan is a selective, competitive, nonpeptide angiotensin II receptor antagonist that blocks the binding of angiotensin II to AT1 receptors, inhibiting vasoconstriction and aldosterone secretion, thereby exerting antihypertensive effects. Its affinity for the AT1 receptor is 12,500 times greater than for the AT2 receptor, demonstrating high selectivity. The compound is hydrolyzed by esterases in the gastrointestinal tract to the active metabolite olmesartan, which interacts with AT1 receptors to reduce peripheral vascular resistance.
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|---|---|
| ln Vitro |
The in vitro activity of olmesartan ethyl ester primarily relates to its transport properties as a prodrug. This compound exists predominantly in an anionic form at intestinal pH and is a substrate for the human organic anion transporting polypeptide 2B1 (OATP2B1), a transporter highly expressed in the small intestine that mediates drug absorption. Studies have shown that the interaction of olmesartan ethyl ester with OATP2B1 is critical for its oral absorption, and OATP2B1 inhibitors (e.g., 50 µM naringin) significantly reduce its area under the plasma concentration-time curve in rats to 76.9%. The parent active metabolite olmesartan exhibits potent AT1 receptor binding with an IC₅₀ of 7.7 nM.
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| ln Vivo |
Following oral administration, olmesartan ethyl ester is rapidly hydrolyzed in the gastrointestinal tract to the active metabolite olmesartan, which exerts antihypertensive effects. Clinical studies have demonstrated that olmesartan (at doses ranging from 10-40 mg) significantly reduces both systolic and diastolic blood pressures, with effects lasting for 24 hours. The pharmacokinetics of olmesartan conform to a two-compartment linear model with first-order absorption and an absorption lag time. The drug is also effective in elderly patients, with randomized and observational studies showing that olmesartan provides effective blood pressure control across the 24-hour dosing interval.
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| Enzyme Assay |
AT1 receptor binding activity of olmesartan ethyl ester can be assessed using radioligand binding assays. The typical protocol is as follows: Membranes from cells expressing human AT1 receptors (e.g., CHO cell membranes) are incubated with [¹²⁵I]-labeled angiotensin II (approximately 0.1 nM) and various concentrations of olmesartan ethyl ester (0.1 nM-100 μM) in binding buffer (50 mM Tris-HCl, pH 7.4, containing 5 mM MgCl₂, 0.1% BSA) at room temperature for 60-120 minutes. The reaction is terminated by rapid vacuum filtration through Whatman GF/C glass fiber filters, followed by three washes with ice-cold buffer. After drying, retained radioactivity on filters is measured using a gamma counter to calculate specific binding inhibition percentages. Competition binding curves are fitted by non-linear regression to obtain IC₅₀ values.
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| Cell Assay |
Cellular assays for olmesartan ethyl ester can utilize the Caco-2 cell monolayer model to evaluate intestinal absorption and transport properties. Caco-2 cells are seeded onto Transwell inserts (0.4 μm pore size) at a density of 1×10⁵ cells/cm² and cultured for 21 days to form tight monolayers (transepithelial electrical resistance >400 Ω·cm²). Various concentrations of olmesartan ethyl ester (1-100 μM) are added to the apical side, and after incubation at 37°C for 2 hours, samples are collected from the basolateral side. Drug concentrations are determined by HPLC-MS/MS to calculate apparent permeability coefficients (Papp). For transporter-mediated uptake studies, OATP2B1-overexpressing HEK293 cells can be used: cells are seeded into 24-well plates at 1×10⁵ cells/well, cultured for 48 hours, then treated with olmesartan ethyl ester (10 μM) at 37°C for 30 minutes. After cell lysis, intracellular drug concentrations are measured by LC-MS/MS to calculate uptake rates.
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| Animal Protocol |
In vivo pharmacodynamic evaluation of olmesartan ethyl ester can be performed using the spontaneously hypertensive rat (SHR) model. Six-to-eight-week-old male SHRs (body weight 200-250 g) are administered olmesartan ethyl ester (1-10 mg/kg) or positive control olmesartan medoxomil by oral gavage, with 6-8 animals per group. Systolic and diastolic blood pressures are measured using the tail-cuff method before administration and at 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-administration to construct antihypertensive effect-time curves. Simultaneously, blood samples are collected from the retro-orbital venous plexus (approximately 0.3 mL per time point), and plasma is separated by centrifugation. Olmesartan concentrations are determined by HPLC-MS/MS to conduct pharmacokinetic-pharmacodynamic correlation analyses. Pharmacokinetic parameters are calculated using non-compartmental models, including Cmax, Tmax, AUC₀₋₂₄, and t₁/₂.
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| ADME/Pharmacokinetics |
Olmesartan ethyl ester is a prodrug that is rapidly hydrolyzed by esterases in the gastrointestinal tract to the active metabolite olmesartan following oral administration. The pharmacokinetics of olmesartan conform to a two-compartment linear model with first-order absorption and an absorption lag time. Mean values of clearance (CL/F) and volume of distribution (V/F) of olmesartan in patients are 0.31565 L/h and 44.5162 L, respectively. Age and creatinine clearance are factors influencing olmesartan clearance, while the volume of distribution depends on age and body surface area. The compound exists predominantly in an anionic form at intestinal pH, facilitating absorption via the OATP2B1 transporter. Coadministration of olmesartan ethyl ester with OATP2B1 inhibitors (e.g., 50 µM naringin) reduces the area under the plasma concentration-time curve of olmesartan to 76.9% in rats.
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| Toxicity/Toxicokinetics |
Toxicological data specifically for olmesartan ethyl ester are limited. As a pharmaceutical impurity, it typically exists only in trace amounts in the drug substance and finished product, so its toxicity contribution at clinical doses is negligible. Olmesartan ethyl ester is not classified as a hazardous material for transport at room temperature; however, reference standard grades (>95% purity) are typically labeled with GHS07 pictograms. Based on structural similarity, this compound may exhibit toxicological characteristics similar to those of olmesartan. The parent compound olmesartan medoxomil is generally well-tolerated in clinical use, with the most common adverse reaction being dizziness (approximately 3% incidence). Other adverse reactions include asthenia, angioedema, hyperkalemia, and elevated blood creatinine levels. Standard chemical safety practices should be followed during handling, including avoiding inhalation, ingestion, or skin contact. The compound can be stored long-term at 2-8°C in sealed, light-protected conditions, and powder can be stored at -20°C for up to 3 years.
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| References |
[1]. Development of efficient one-pot three-component assembly of trityl olmesartan medoxomil. Bioorg Med Chem. 2018 Aug 7;26(14):4348-4359.
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| Molecular Formula |
C26H30N6O3
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|---|---|
| Molecular Weight |
474.55
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| Exact Mass |
474.238
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| CAS # |
144689-23-6
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| Related CAS # |
144689-24-7; 1347262-29-6 (methyl ester ); 144689-63-4 (medoxomil)
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| PubChem CID |
10600595
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.135
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
35
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| Complexity |
686
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCCC1N(CC2=CC=C(C3=C(C4N=NNN=4)C=CC=C3)C=C2)C(C(OCC)=O)=C(C(C)(C)O)N=1
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| InChi Key |
RYYGFMDEVYVZGY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H30N6O3/c1-5-9-21-27-23(26(3,4)34)22(25(33)35-6-2)32(21)16-17-12-14-18(15-13-17)19-10-7-8-11-20(19)24-28-30-31-29-24/h7-8,10-15,34H,5-6,9,16H2,1-4H3,(H,28,29,30,31)
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| Chemical Name |
ethyl 5-(2-hydroxypropan-2-yl)-2-propyl-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazole-4-carboxylate
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| Synonyms |
Olmesartan Ethyl Ester; Olmesartan Acid Ethyl Ester; Olmesartan Ethyl Ester Impurity; Ethyl 1-((2'-(1h-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-4-(2-hydroxypropan-2-yl)-2-propyl-1H-imidazole-5-carboxylate;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1073 mL | 10.5363 mL | 21.0726 mL | |
| 5 mM | 0.4215 mL | 2.1073 mL | 4.2145 mL | |
| 10 mM | 0.2107 mL | 1.0536 mL | 2.1073 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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