Acebutolol
N-(3-acetyl-4-(2-hydroxy-3-(isopropylaMino)propoxy)phenyl)butyraMide · Prent · Sectral · ACEBUTOLOL · Acebuprolol · Acebutololum · Acetobutolol · dl-Acebutolol
식별자 및 물리적 특성
| CAS No. | 37517-30-9 |
|---|---|
| 분자식 | C18H28N2O4 |
| 평균 분자량 | 336.4 g/mol |
| 단동위원소 질량 | 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 |
화학 및 물리적 성질
| XLogP | 1.7 |
|---|---|
| 극성 표면적 | 87.7 |
| 수소 결합 공여자 수 | 3 |
| 수소 결합 수용자 수 | 5 |
| 회전 가능 결합 수 | 10 |
| 무거운 원자 수 | 24 |
| 형식 전하 | 0 |
| 복잡도 | 400 |
| 의약품 | Pharmaceuticals |
| LogP(분배 계수) | 1.71.71 |
| 용해도 | 1.72e-01 g/LDMF: 10 mg/mL,DMSO: 5 mg/mL,Ethanol: 5 mg/mL,PBS (pH 7.2): 0.3 mg/mL |
| Human Drugs | Breast FeedingLactationMilk, HumanAntihypertensive AgentsAdrenergic Beta-AntagonistsAntiarrhythmicsPharmaceuticals |
| 녹는점 | 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)] |
| 끓는 점 | 472.9°C (rough estimate) |
| 밀도 | 1.1748 (rough estimate) |
| 굴절률 | 1.5700 (estimate) |
| 저장 조건 | -20°C Freezer |
| 물리적 상태 | 고체 |
| pKa(산도 계수) | pKa 9.40 (Uncertain) |
| 색상 | 크리스탈 |
| 용해도 | 259mg/L |
| NIST | Acebutolol(37517-30-9) |
| EPA | Butanamide, N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]- (37517-30-9) |
화학적 성질
Crystalline Solid
안전 및 규제
| GHS 분류 | 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. |
|---|---|
| 기타 안전 정보 | 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. |
용도
용도
Cardioselective adrenergic blocker. Antihypertensive; antianginal; antiarrhythmic (class II)
일반 설명
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.