アセブトロール
アセトブトロール · アセブトロール · DL-アセブトロール · rac-N-[3-アセチル-4-[(R*)-2-ヒドロキシ-3-[(1-メチルエチル)アミノ]プロポキシ]フェニル]ブタンアミド · rac-N-[3-アセチル-4-[(R*)-2-ヒドロキシ-3-(イソプロピルアミノ)プロポキシ]フェニル]ブタンアミド · (±)-アセブトロール · (±)-N-[3-アセチル-4-[2-ヒドロキシ-3-[(1-メチルエチル)アミノ]プロポキシ]フェニル]ブタンアミド · N-[4-[2-ヒドロキシ-3-(イソプロピルアミノ)プロポキシ]-3-アセチルフェニル]ブタンアミド
識別子と物理属性
| CAS No. | 37517-30-9 |
|---|---|
| 分子式 | C18H28N2O4 |
| 平均分子量 | 336.4 g/mol |
| 単同位体質量 | 336.20490738 g/mol |
| SMILES | CCCC(=O)Nc1ccc(OCC(O)CNC(C)C)c(C(C)=O)c1 |
| InChIKey | GOEMGAFJFRBGGG-UHFFFAOYSA-N |
| PubChem CID | 1978 |
| ChEMBL | CHEMBL642 |
| ChEBI | CHEBI:2379 |
| EC No. | 253-539-0 |
| DTXSID | DTXSID2048539 |
| 現地名 | アセブトロール |
化学・物理的性質
| XLogP | 1.7 |
|---|---|
| 極性表面積 | 87.7 |
| 水素結合供与体数 | 3 |
| 水素結合受容体数 | 5 |
| 回転可能結合数 | 10 |
| 重原子数 | 24 |
| 形式電荷 | 0 |
| 複雑度 | 400 |
| 医薬品 | Pharmaceuticals |
| LogP（分配係数） | 1.71.71 |
| 溶解度 | 1.72e-01 g/LDMF: 10 mg/mL,DMSO: 5 mg/mL,Ethanol: 5 mg/mL,PBS (pH 7.2): 0.3 mg/mL259mg/L |
| Human Drugs | Breast FeedingLactationMilk, HumanAntihypertensive AgentsAdrenergic Beta-AntagonistsAntiarrhythmicsPharmaceuticals |
| 融点 | 136-138119 - 123 °C119-123°C |
| Physical Description | Solid |
| Dissociation Constants | 9.529.67 |
| Collision Cross Section | 187.43 Ų [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]190.2 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)] |
| 沸点 | 472.9°C (rough estimate) |
| 密度 | 1.1748 (rough estimate) |
| 屈折率 | 1.5700 (estimate) |
| 貯蔵条件 | -20°C Freezer |
| 外観・状態 | A solid |
| pKa（酸解離定数） | pKa 9.40 (Uncertain) |
| 色 | クリスタル |
| CAS データベース | 37517-30-9(CAS DataBase Reference) |
| NISTの化学物質情報 | Acebutolol(37517-30-9) |
| EPAの化学物質情報 | Butanamide, N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]- (37517-30-9) |
化学的特性
Crystalline Solid
安全性と法規制
| GHS 分類 | H362 (100%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]P203, P260, P263, P264, P270, and P318 (click each P-code to see the statement)The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory. |
|---|---|
| その他の安全情報 | IMAP assessments - Butanamide, N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]-, (.+-.)-: Environment tier I assessment |
| Hazard Classes and Categories | Lact. (100%) |
| Hepatotoxicity | Acebutolol is associated with a low rate of mild-to-moderate elevations of serum aminotransferase levels during treatment. These enzyme elevations are usually asymptomatic and transient and resolve even with continuation of therapy. There have been few documented cases of clinically apparent, acute liver injury attributed to acebutolol. The time to onset of injury was typically between 1 and 6 weeks of starting. The pattern of liver enzyme elevations was usually hepatocellular with an acute hepatitis-like presentation, although some cases present with a mixed pattern of enzymes. Fever commonly accompanied the liver injury, but usually without rash and eosinophia. Acebutolol is known to induce autoantibodies such as antinuclear antibody in 10% to 30% of patients, some of whom develop a lupus-like syndrome with fatigue, skin rash and arthralgias. Serum enzyme elevations may accompany this syndrome, but jaundice and symptoms of liver injury are uncommon. The published cases of hepatotoxicity due to acebutolol were relatively mild, self-limited and recovery was rapid upon stopping. Rechallenge resulted in rapid recurrence of injury. |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)acebutololDILI PositiveOralDOI:10.1016/j.drudis.2019.09.022 |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| EPA Human Health Benchmarks for Pharmaceuticals | Acebutolol4.719.7An optimal response is usually achieved with dosages of 400 to 800 mg per day, although some patients have been maintained on as little as 200 mg per day.Data used to generate the benchmarks include the following: Lowest Daily Dose (LDD): 200 mg/day, Lowest Therapeutic Dose (LTD): 2.5 mg/kg-day, and Screening Dose: 0.001 mg/kg-day.27-Dec-20 |
| 毒性 | TDLo orl-wmn: 152 mg/kg:CVS,BPR JTCTDW 20,69,83 |
用途
使用
Cardioselective adrenergic blocker. Antihypertensive; antianginal; antiarrhythmic (class II)
一般的な説明
Acebutolol is one of the very few β-blockers whosemetabolite plays a significant role in its pharmacological actions.This drug is absorbed well from the gastrointestinaltract, but it undergoes extensive first-pass metabolic conversionto diacetolol by hydrolytic conversion of the amidegroup to the amine, followed by acetylation of the amine. After oral administration, plasma levels of diacetololare higher than those of acebutolol. Diacetolol is also aselective β1-blocker with partial agonistic activity; it has littlemembrane-stabilizing activity. It has a longer half-life (8–12hours) than the parent drug and is excreted by the kidneys.