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エソメプラゾール
エソメプラゾール · Esomeprazol · EsoMaprozole · 5-Methoxy-2-(4-Methoxy-3,5-diMethyl-pyridin-2-ylMethanesulfinyl)-1H-benzoiMidazole · 5-Methoxy-2-(((4-Methoxy-3,5-diMethylpyridin-2-yl)Methyl)sulfinyl)-1H-benzo[d]iMidazole · (R)-5-Methoxy-2-(((4-Methoxy-3,5-diMethylpyridin-2-yl)Methyl)sulfinyl)-1H-benzo[d]iMidazole · (S)-6-Methoxy-2-(((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazole · (RelCpd F)
識別子と物理属性
| CAS No. | 119141-88-7 |
|---|---|
| 分子式 | C17H19N3O3S |
| 平均分子量 | 345.424 g/mol |
| 単同位体質量 | 345.11471247 g/mol |
| SMILES | COc1ccc2nc([S@@](=O)Cc3ncc(C)c(OC)c3C)[nH]c2c1 |
| InChIKey | SUBDBMMJDZJVOS-DEOSSOPVSA-N |
| PubChem CID | 9568614 |
| ChEMBL | CHEMBL1201320 |
| ChEBI | CHEBI:50275 |
| EC No. | 643-098-6 |
| DTXSID | DTXSID4044292 |
| 現地名 | エソメプラゾール |
化学・物理的性質
| XLogP | 2.2 |
|---|---|
| 極性表面積 | 96.3 |
| 水素結合供与体数 | 1 |
| 水素結合受容体数 | 6 |
| 回転可能結合数 | 5 |
| 重原子数 | 24 |
| 形式電荷 | 0 |
| 複雑度 | 453 |
| LogP（分配係数） | 0.6 |
| 溶解度 | Very slightly soluble in waterDMF: 30 mg/ml,DMSO: 20 mg/ml,Ethanol: 10 mg/ml,PBS (pH 7.2): 10 mg/ml |
| Decomposition | Hazardous decomposition products formed under fire conditions. - Carbon oxides, nitrogen oxides (NOx), Sulphur oxides, Magnesium oxide |
| 融点 | 155 |
| Physical Description | Solid |
| Other Experimental Properties | White to slightly colored crystalline powder. Slightly soluble in waterstability ... is a function of pHit degrades rapidly in acidic media but has acceptable stability under alkaline conditionshalf-lives of 19 and 8 hrs at 25 and 37 °C, respectively /Esomeprazole magnesium/White to almost white crystalline powdersoluble in water /Esomeprazole strontium/... for injection is supplied as a sterile, freeze-dried, white to off-white, porous cake or powder. ... The stability of esomeprazole sodium in aqueous solution is strongly pH dependent. /Esomeprazole sodium/ |
| 比旋光度 | D20 -155° (c = 0.5 in chloroform) |
| 沸点 | 600.0±60.0 °C(Predicted) |
| 密度 | 1.37±0.1 g/cm3(Predicted) |
| 貯蔵条件 | Sealed in dry,Room Temperature |
| 外観・状態 | A solid |
| pKa（酸解離定数） | 8.50±0.10(Predicted) |
| ヘンリー定数 | 3.3×1013 mol/(m3Pa) at 25℃, HSDB (2015) |
| InChI | InChI=1S/C17H19N3O3S/c1-10-8-18-15(11(2)16(10)23-4)9-24(21)17-19-13-6-5-12(22-3)7-14(13)20-17/h5-8H,9H2,1-4H3,(H,19,20)/t24-/m0/s1 |
| InChIKey | SUBDBMMJDZJVOS-DEOSSOPVSA-N |
| SMILES | C1([S@](CC2=NC=C(C)C(OC)=C2C)=O)NC2=CC(OC)=CC=C2N=1 |
| CAS データベース | 119141-88-7(CAS DataBase Reference) |
安全性と法規制
| GHS 分類 | WarningH312 (100%): Harmful in contact with skin [Warning Acute toxicity, dermal]H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]H335 (100%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposureRespiratory tract irritation]H412 (100%): Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]P261, P264, P264+P265, P271, P272, P273, P280, P302+P352, P304+P340, P305+P351+P338, P317, P319, P321, P332+P317, P333+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory. |
|---|---|
| 火災の可能性 | Not flammable or combustible. |
| FDA 要件 | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including esomeprazole magnesium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Esomeprazole magnesium/The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including esomeprazole sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Esomeprazole sodium/The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including esomeprazole strontium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Esomeprazole strontium/ |
| Hazard Classes and Categories | Skin Irrit. 2 (100%)Skin Sens. 1 (100%)Eye Irrit. 2 (100%)STOT SE 3 (100%)Aquatic Chronic 3 (100%) |
| Skin, Eye, and Respiratory Irritations | May cause eye irritation. May be harmful if inhaled. May cause respiratory tract irritation. Harmful if absorbed through skin. May cause skin irritation. |
| 保管条件 | Store NEXIUM at room temperature between 68 °F to 77 °F (20 °C to 25 °C). Keep the container of NEXIUM closed tightly. |
| 相互作用 | In a single-dose study, concomitant administration of omeprazole 20 mg and sucralfate 1 g resulted in delayed absorption of omeprazole and decreased omeprazole bioavailability by 16%. Proton-pump inhibitors should be administered at least 30 minutes before sucralfate.Pharmacokinetic interaction with omeprazole (decreased plasma concentrations and AUC of rilpivirine).32 343 Concomitant use of other proton-pump inhibitors also may result in decreased plasma concentration of rilpivirine.343 Concomitant use of rilpivirine and proton-pump inhibitors is contraindicated.Concomitant use of omeprazole 40 mg once daily and atazanavir (with or without low-dose ritonavir) results in a substantial decrease in plasma concentrations of atazanavir and possible loss of the therapeutic effect of the antiretroviral agent or development of drug resistance. Concomitant use of omeprazole 40 mg once daily (administered 2 hours before atazanavir) and atazanavir 400 mg once daily decreased the AUC and peak plasma concentration of atazanavir by 94 and 96%, respectively. The manufacturer of esomeprazole states that concomitant administration with atazanavir is not recommended. If atazanavir is administered in an antiretroviral treatment-naive patient receiving a proton-pump inhibitor, a ritonavir-boosted regimen of 300 mg of atazanavir once daily with ritonavir 100 mg once daily with food is recommended. The dose of the proton-pump inhibitor should be administered approximately 12 hours before ritonavir-boosted atazanavirthe dose of the proton-pump inhibitor should not exceed omeprazole 20 mg daily (or equivalent). Concomitant use of proton-pump inhibitors with atazanavir is not recommended in antiretroviral treatment-experienced patients.Concomitant use of omeprazole 20 mg once daily and digoxin in healthy individuals increased digoxin bioavailability by 10% (up to 30% in some individuals). Because esomeprazole is an enantiomer of omeprazole, concomitant use of esomeprazole with digoxin is expected to increase systemic exposure to digoxintherefore, monitoring for manifestations of digoxin toxicity may be required during such concomitant use.For more Interactions (Complete) data for Esomeprazole (7 total), please visit the HSDB record page. |
| 健康影響 | Blurred vision, confusion, drowsiness, dry mouth, flushing headache, nausea, rapid heartbeat, sweating.may include bone rebuild interference and B12 vitamin reduction. [Wikipedia] |
| 環境中動態 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1500(SRC), determined from a structure estimation method(2), indicates that esomeprazole is expected to have low mobility in soil(SRC). The estimated pKa of esomeprazole is 4.78(3), indicating that this compound will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of neutral esomeprazole from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.1X10-19 atm-cu m/mole(SRC), using a fragment constant estimation method(5). The cation form of esomeprazole will not volatilize(SRC). Esomeprazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2013).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1500(SRC), determined from a structure estimation method(2), indicates that esomeprazole is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 4.78(3) indicates esomeprazole will partially exist in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces of the ion form is not expected to be an important fate process(SRC). Volatilization of the neutral form from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 3.0X10-19 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 14(SRC), from an estimated log Kow of 3.40(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2013).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), esomeprazole, which has an estimated vapor pressure of 1.2X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase esomeprazole may be removed from the air by wet and dry deposition(SRC). Esomeprazole does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to/may be susceptible to direct photolysis by sunlight(SRC). |
| 暴露経路 | OralThe delayed-release capsule are enteric-coated (as omeprazole is acid-labile) so the absorption of omprazole begins once the granules leave the stomach. Absorption is rapid. Peak plasma levels occur within 0.5 - 3.5 hours. The absolute bioavailability (compared with intravenous administration) of the delayed-release capsule is 30-40% at doses of 20 - 40 mg, due to presystemic metabolism. This value increases slightly when given repeatedly. Based on a relative bioavailability study, the AUC and Cmax of PRILOSEC (omeprazole magnesium) for Delayed-Release Oral Suspension were 87% and 88% of those for PRILOSEC Delayed-Release Capsules, respectively. Interestingly, when the 40 mg delayed release capsule is given with or without applesauce, it is bioequivalent. However, when the 20 mg delayed release capsule is given with the same conditions, it is not bioequivalent. When the same capsule is given to the elderly, bioavailability increases. Omeprazole was 76% bioavailable. |
| 毒性の概要 | Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H<sup>+</sup>/K<sup>+</sup>-ATPase in the gastric parietal cell. By acting specifically on the proton pump, Esomeprazole blocks the final step in acid production, thus reducing gastric acidity.Omeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H<sup>+</sup>/K<sup>+</sup>-ATPase in the gastric parietal cell. By acting specifically on the proton pump, omeprazole blocks the final step in acid production, thus reducing gastric acidity. |
| Signs and Symptoms | Blurred vision, confusion, drowsiness, dry mouthflushingheadache, nausea, rapid heartbeat, sweating.Symptoms of overdose include confusion, drowsiness, blurred vision, tachycardia, nausea, diaphoresis, flushing, headache, and dry mouth. |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of esomeprazole can be estimated to be 1500(SRC). According to a classification scheme(2), this estimated Koc value suggests that esomeprazole is expected to have low mobility in soil. The estimated pKa of esomeprazole is 4.78(3), indicating that this compound will partially exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). |
| Artificial Pollution Sources | Esomeprazole's production and administration as an anti-ulcer agent(1) may result in its release to the environment through various waste streams(SRC). |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Environmental Bioconcentration | An estimated BCF of 14 was calculated in fish for esomeprazole(SRC), using an estimated log Kow of 3.40(1) and a regression-derived equation(1). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC). |
| Volatilization from Water/Soil | An estimated pKa of 4.78(1) indicates esomeprazole will partially exist in the cation form at pH values of 5 to 9 and, therefore, volatilization from water and moist soil surfaces of the ion form is not expected to be an important fate process(SRC). The Henry's Law constant for esomeprazole is estimated as 3.0X10-19 atm-cu m/mole(SRC) using a fragment constant estimation method(2). This Henry's Law constant indicates that neutral form of esomeprazole is expected to be essentially nonvolatile from water and moist soil surfaces(3). Esomeprazole is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-11 mm Hg(SRC), determined from a fragment constant method(4). |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ The carcinogenic potential of NEXIUM was assessed using studies of omeprazole, of which esomeprazole is an enantiomer. In two 24-month oral carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44, and 141 mg/kg/day (about 0.7 to 57 times the human dose of 20 mg/day expressed on a body surface area basis) produced gastric ECL cell carcinoids in a dose-related manner in both male and female ratsthe incidence of this effect was markedly higher in female rats, which had higher blood levels of omeprazole. Gastric carcinoids seldom occur in the untreated rat. In addition, ECL cell hyperplasia was present in all treated groups of both sexes. In one of these studies, female rats were treated with 13.8 mg omeprazole/kg/day (about 5.6 times the human dose on a body surface area basis) for 1 year, then followed for an additional year without the drug. No carcinoids were seen in these rats. An increased incidence of treatment-related ECL cell hyperplasia was observed at the end of 1 year (94% treated vs. 10% controls). By the second year the difference between treated and control rats was much smaller (46% vs. 26%) but still showed more hyperplasia in the treated group. Gastric adenocarcinoma was seen in one rat (2%). No similar tumor was seen in male or female rats treated for 2 years. For this strain of rat no similar tumor has been noted historically, but a finding involving only one tumor is difficult to interpret. A 78-week mouse carcinogenicity study of omeprazole did not show increased tumor occurrence, but the study was not conclusive./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproductive studies have been performed in rats at oral doses up to 280 mg/kg/day (about 57 times the human dose on a body surface area basis) and in rabbits at oral doses up to 86 mg/kg/day (about 35 times the human dose on a body surface area basis) and have revealed no evidence of impaired fertility or harm to the fetus due to esomeprazole./GENOTOXICITY/ Esomeprazole was negative in the Ames mutation test, in the in vivo rat bone marrow cell chromosome aberration test, and the in vivo mouse micronucleus test. Esomeprazole, however, was positive in the in vitro human lymphocyte chromosome aberration test. |
| 税関コード | 29339900 |
| 有害物質データ | 119141-88-7(Hazardous Substances Data) |
用途
説明
Esomeprazole, formulated as a magnesium salt, reached the market as a treatment for acid-related diseases such as gastro-esophageal reflux (GERD) disease including peptic ulcer disease and reflux esophagitis. Esomeprazole (formerly perprazole) is the active (S)- enantiomer of omeprazole (1988) and the first proton pump inhibitor developed as an optical isomer. It can be obtained by several routes such as asymmetric oxidation of the pro-chiral pyridylmethyl benzimidazole sulfide, separation from the racemic sulfoxide by chiral chromatography or separation of a diastereomeric mixture obtained from the racemic compound and a chiral acid, followed by hydrolysis. Biochemical studies have shown that esomeprazole irreversibly inhibits the gastric H+/K+-adenosine triphosphatase (ATPase), an enzyme system involved at the secretory surface of the stomach’s parietal cells responsible for the secretion of gastric acid. Compared with racemic omeprazole in healthy subjects, esomeprazole has higher bioavailability, is absorbed more rapidly and exhibits a more uniform and predictable dose-response with higher plasma levels, leading to less inter-individual variability between slow and rapid metabolizers. In extensive clinical trials in patients suffering from GERD symptoms, esomeprazole provided superior acid control and significantly reduced the healing time compared to omeprazole.
使用
(-)-Omeprazole can be used to treat migraine.
使用
Esomeprazole is used to treat certain stomach and esophagus problems (such as acid reflux, ulcers). It works by decreasing the amount of acid your stomach makes. It relieves symptoms such as heartburn, difficulty swallowing, and persistent cough.