基本情報
- CAS
155974-00-8- 標準SMILES
COc1cc2c(cc1OC)CC(=O)N(CCCN(C)C[C@H]1Cc3cc(OC)c(OC)cc31)CC2- InChIKey
ACRHBAYQBXXRTO-OAQYLSRUSA-N- 分子式
- C27H36N2O5
- 平均分子量
- 468.6 g/mol
- 単同位体質量
- 468.26242225
概要
Ivabradine is a member of the class of benzazepines that is 7,8-dimethoxy-1,3,4,5-tetrahydro-3-benzazepin-2-one in which the amide hydrogen is replaced by a [{[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino]propyl} group. Used (as its hydrochloride salt) to treat patients with angina who have intolerance to beta blockers and/or heart failure. It has a role as a cardiotonic drug. It is an aromatic ether, a benzazepine, a carbobicyclic compound and a tertiary amino compound. It is a conjugate base of an ivabradine(1+).
名称と識別子
- 優先名称
- Ivabradine
- IUPAC
- 3-[3-[[(7S)-3,4-dimethoxy-7-bicyclo[4.2.0]octa-1,3,5-trienyl]methyl-methylamino]propyl]-7,8-dimethoxy-2,5-dihydro-1H-3-benzazepin-4-one
- 現地名
- イバブラジン
- 英語名
- Ivabradine
- 分子式
- C27H36N2O5
- 分子量
- 468.59
名称と別名
Ivabradine155974-00-8S-16257IvabradinaS 162573H48L0LPZQDTXSID20482403-[3-({[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}(methyl)amino)propyl]-7,8-dimethoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-2-oneCHEBI:85966s16257(S)-3-(3-(((3,4-Dimethoxybicyclo(4.2.0)octa-1,3,5-trien-7-yl)methyl)methylamino)propyl)-1,3,4,5-tetrahydro-7,8-dimethoxy-2H-3-benzazepin-2-one2H-3-Benzazepin-2-one, 3-(3-(((3,4-dimethoxybicyclo(4.2.0)octa-1,3,5-trien-7-yl)methyl)methylamino)propyl)-1,3,4,5-tetrahydro-7,8-dimethoxy-, (S)-
名称をさらに表示
イバブラジン3-[3-[N-[[(7S)-3,4-ジメトキシビシクロ[4.2.0]オクタ-1,3,5-トリエン-7-イル]メチル]-N-メチルアミノ]プロピル]-7,8-ジメトキシ-4,5-ジヒドロ-1H-3-ベンゾアゼピン-2(3H)-オン3-[3-({[(7S)-3,4-ジメトキシビシクロ[4.2.0]オクタ-1(6),2,4-トリエン-7-イル]メチル}(メチル)アミノ)プロピル]-7,8-ジメトキシ-2,3,4,5-テトラヒドロ-1H-3-ベンゾアゼピン-2-オン7,8-ジメトキシ-4,5-ジヒドロ-3-[3-[メチル[[(7S)-3,4-ジメトキシビシクロ[4.2.0]オクタ-1,3,5-トリエン-7-イル]メチル]アミノ]プロピル]-1H-3-ベンゾアゼピン-2(3H)-オン3-[3-[[[(7S)-3,4-ジメトキシビシクロ[4.2.0]オクタ-1,3,5-トリエン-7-イル]メチル]メチルアミノ]プロピル]-1,3,4,5-テトラヒドロ-7,8-ジメトキシ-2H-3-ベンゾアゼピン-2-オン
物性
構造計算による物性
- XLogP
- 2.4
- 極性表面積
- 60.5 Ų
- 水素結合供与体数
- 0
- 水素結合受容体数
- 6
- 回転可能結合数
- 10
- 重原子数
- 34
- 形式電荷
- 0
- 複雑度
- 663
実験および物理化学的性質
DrugsPharmaceuticals -> Listed in ZINC15
Human Drugs
Breast Feeding; Lactation; Milk, Human; Cardiovascular Agents
FDA approved drugs -> Active ingredient
EMA approved medicines: Human medicine
EMA approved medicines: Human medicine
EMA approved medicines: Human medicine
EMA approved medicines: Human medicine
Endocrine DisruptorsPotential endocrine disrupting compound
物理化学的性質
- 沸点
- 626.9 · 626.9±55.0 °C(Predicted)
- 比重(密度)
- 1.146 · 1.146±0.06 g/cm3(Predicted)
- 酸解離定数(Pka)
- 8.77 · 8.77±0.50(Predicted)
安全と法規制
安全情報は参考情報です。供給元の安全データシート（SDS）、適用法令、専門家による評価に代わるものではありません。
毒性情報
HepatotoxicityIn large preregistration clinical trials, similar proportions of patients taking ivabradine as taking placebo developed ALT elevations [15% vs 17%] while ALT elevations above 5 times the upper limit of normal were uncommon [
Adverse EffectsThe most common adverse effects associated with ivabradine administration, according to the product label, include bradycardia, atrial fibrillation, hypertension, and phosphenes.
Toxicity SummarySigns and Symptoms of Overdose
Effects During Pregnancy and Lactation◉ Summary of Use during Lactation
化学と産業
薬理情報
ATC Code
C01EB17
C - Cardiovascular system
QC - Cardiovascular system
Protein Binding70% bound to plasma proteins.
Pharmacodynamics
The funny channels (If) open during repolarization and close during depolarization, making ivabradine's activity dependent on heart rate or the closing and opening of the channels. Therefore ivabradine exhibits use-dependence and is more pharmacologically active at higher heart rates. Ivabradine exhibits a linear dose-dependent heart-rate lowering activity (bradycardic effect) until a maximum dose of 30-40mg. At higher doses, the concentration of ivabradine tends to plateau, reducing risk of serious sinus bradycardia. It has been shown that the metabolite of ivabradine lowers heart rate as well, contributing to ivabradine's overall effect.
Mechanism of Action
Ivabradine lowers heart rate by selectively inhibiting If channels ("funny channels") in the heart in a concentration-dependent manner without affecting any other cardiac ionic channels (including calcium or potassium). Ivabradine binds by entering and attaching to a site on the channel pore from the intracellular side and disrupts If ion current flow, which prolongs diastolic depolarization, lowering heart rate. The If currents are located in the sinoatrial node and are the home of all cardiac pacemaker activity. Ivabradine therefore lowers the pacemaker firing rate, consequently lowering heart rate and reducing myocardial oxygen demand. This allows for an improved oxygen supply and therefore mitigation of ischemia, allowing for a higher exercise capacity and reduction in angina episodes.
Biological Half-Life2 hours.
Metabolism/Metabolites
Ivabradine is extensively metabolized by oxidation in the gut and liver by cytochrome P450 3A4 enzyme. Its active metabolite, N-desmethylated derivative, is also metabolized by CYP 3A4. Ivabradine's affinity for CYP 3A4 is low, making it unlikely to affect the metabolism of other drugs; however potent inhibitors or inducers of CYP 3A4 may affect ivabradine's plasma concentration and pharmacodynamic effects and should not be co-administered.
関連反応
19 件
化合物ノート
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