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ランジオロール

Landiolol

HCID 114905
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基本情報概要名称と識別子物性化学と産業関連反応化合物ノート
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基本情報

CAS
133242-30-5
標準SMILES
CC1(C)OC[C@@H](COC(=O)CCc2ccc(OC[C@@H](O)CNCCNC(=O)N3CCOCC3)cc2)O1
InChIKey
WMDSZGFJQKSLLH-RBBKRZOGSA-N
分子式
C25H39N3O8
平均分子量
509.6 g/mol
単同位体質量
509.27371521

概要

Landiolol is a member of morpholines.

名称と識別子

優先名称
Landiolol
IUPAC
[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 3-[4-[(2S)-2-hydroxy-3-[2-(morpholine-4-carbonylamino)ethylamino]propoxy]phenyl]propanoate
現地名
ランジオロール
英語名
Landiolol
分子式
C25H39N3O8
分子量
509.59

名称と別名

Landiolol133242-30-5ONO-1101Ono 1101[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 3-[4-[(2S)-2-hydroxy-3-[2-(morpholine-4-carbonylamino)ethylamino]propoxy]phenyl]propanoateLDLL60062NWQ924LHLDLL-600AOP200704AOP-200704DTXSID10158026Benzenepropanoic acid, 4-((2S)-2-hydroxy-3-((2-((4-morpholinylcarbonyl)amino)ethyl)amino)propoxy)-, ((4S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl ester
名称をさらに表示
[(4S)-2,2-ジメチル-1,3-ジオキソラン-4-イル]メチル 3-{4-[(2S)-2-ヒドロキシ-3-({2-[(モルホリン-4-カルボニル)アミノ]エチル}アミノ)プロポキシ]フェニル}プロパノアート4-[(S)-2-ヒドロキシ-3-[[2-[(モルホリノカルボニル)アミノ]エチル]アミノ]プロポキシ]ベンゼンプロパン酸[(S)-2,2-ジメチル-1,3-ジオキソラン-4-イル]メチル4-[(S)-2-ヒドロキシ-3-[[2-[(モルホリノカルボニル)アミノ]エチル]アミノ]プロポキシ]ベンゼンプロパン酸[(S)-2,2-ジメチル-1,3-ジオキソラン-4α-イル]メチルランジオロールONO1101Landiolol D8Landiolol USP/EP/BPLandiolol HCL EP USP((S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl 3-(4-((S)-2-hydroxy-3-((2-(morpholine-4-carboxamido)ethyl)amino)propoxy)phenyl)propanoate((–)-[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl-3-{4-[(S)-2-hydroxy-3-(2-morpholino-carbonylamino)ethylamino] propoxy}phenylpropionate)
(-)-((S)-2,2-Dimethyl-1,3-dioxolan-4-yl)methyl p-((S)-2-hydroxy-3-((2-(4-morpholinecarboxamido)ethyl)amino)propoxy)hydrocinnamatelandiololum((4S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl 3-(4-((2S)-2-hydroxy-3-(2-(morpholine-4-carbonylamino)ethylamino)propoxy)phenyl)propanoateBenzenepropanoic acid, 4-[(2S)-2-hydroxy-3-[[2-[(4-morpholinylcarbonyl)amino]ethyl]amino]propoxy]-, [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl esterRefChem:152225DTXCID2080517C07AB14((4S)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl 3-(4-((2S)-2-hydroxy-3-((2-((morpholine-4-carbonyl)amino)ethyl)amino)propoxy)phenyl)propanoate

データベース識別子

CAS
133242-30-5
PubChem CID
114905
DTXSID
DTXSID10158026
ChEMBL
CHEMBL1742466
ChEBI
CHEBI:135809
UNII
62NWQ924LH
Nikkaji
J477.155I

物性

構造計算による物性補完中

XLogP
0.1
極性表面積
128 Ų
水素結合供与体数
3
水素結合受容体数
9
回転可能結合数
14
重原子数
36
形式電荷
0
複雑度
666

実験および物理化学的性質

DrugsPharmaceuticals -> Listed in ZINC15
Melting Point122-125

物理化学的性質

沸点
727.5 · 727.5±60.0 °C(Predicted)
比重(密度)
1.201 · 1.201±0.06 g/cm3(Predicted)
酸解離定数(Pka)
13.73 · 13.73±0.20(Predicted)
InChIKey
WMDSZGFJQKSLLH-RBBKRZOGSA-N
SMILES
C1(CCC(OC[C@@H]2COC(C)(C)O2)=O)=CC=C(OC[C@@H](O)CNCCNC(N2CCOCC2)=O)C=C1

化学と産業

薬理情報

ATC Code · 2 件

C - Cardiovascular system

QC - Cardiovascular system

Protein BindingLandiolol protein binding is less than 10% and dose-dependent.
Pharmacodynamics · 1 件

Landiolol has a very short duration of action and a rapid onset and offset of action. It is a cardio-selective drug that produces a negative chronotropic effect with weaker negative inotropic effects and less hypotensive effects compared to other beta blockers. Due to its selectivity towards beta-1 adrenoceptors over beta-2- or beta-3 adrenoceptors, landiolol has reduces heart rate without causing a profound decrease in mean arterial blood pressure. In preclinical and clinical studies, landiolol controlled tachycardia in an ultra-short-acting manner with fast onset and offset of action, while further demonstrating anti-ischemic and cardioprotective effects. Landiolol does not exhibit any membrane-stabilizing activity or intrinsic sympathomimetic activity at the approved recommend dosage in vitro.

Mechanism of Action · 1 件

Beta (β)-1 adrenoceptors are predominantly found in the myocardium, to which endogenous catecholamines, epinephrine and norepinephrine, bind. These receptors activate intracellular molecules and signalling pathways, such as the stimulatory G protein (Gs) and cyclic AMP. Landiolol is a selective beta-1 adrenoreceptor antagonist that inhibits the positive chronotropic effects of the catecholamines. Landiolol reduces the sympathetic drive, resulting in the reduction of heart rate, decreasing the spontaneous firing of ectopic pacemakers, while slowing the conduction and increasing the refractory period of the atrioventricular node.

Biological Half-LifeThe elimination half-life of landiolol was 3.2 minutes after a single landiolol bolus administration of 100 mcg/kg, and 4.52 minutes after a 20 hour continuous landiolol infusion of 40 mcg/kg/min.
Metabolism/Metabolites · 1 件

Landiolol is primarily metabolized by pseudocholinesterases and carboxylesterases in the plasma. The ester moiety of landiolol is hydrolyzed to release a ketal: this alcoholic component is further cleaved to yield glycerol and acetone, and the carboxylic acid component (metabolite M1), which subsequently undergoes betaoxidation to form metabolite M2 (a substituted benzoic acid). The pharmacological activity of M1 and M2 are negligible, with M1 having less than 1/40th of the pharmacological activity of landiolol. M1 AUC<sub>0-inf</sub> is approximately 12 times greater than landiolol.

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化合物ノート

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FDA Pharmacological Classification · 6 件

62NWQ924LH

LANDIOLOL

Established Pharmacologic Class [EPC] - beta-Adrenergic Blocker

Mechanisms of Action [MoA] - Adrenergic beta1-Antagonists

Landiolol is a beta-Adrenergic Blocker. The mechanism of action of landiolol is as an Adrenergic beta1-Antagonist.

LANDIOLOL

MeSH Pharmacological Classification · 2 件

Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.

Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.

Absorption, Distribution and Excretion · 4 件

In healthy volunteers, the mean peak plasma concentrations (Cmax) at the dose of 9.3 mcg/kg/min, 18.6 mcg/kg/min, and 37.3 mcg/kg/min were 0.2 mcg/mL, 0.5 mcg/mL, and 1.0 mcg/mL, respectively. In patients with atrial fibrillation or atrial flutter, the Cmax ranged from 0.52 to 1.77 mcg/mL at the dose of 37.3 mcg/kg/min. Landiolol reached steady-state values approximately 15 minutes after initiation of the infusion.

The main route of excretion of landiolol is renal elimination. Approximately 50 to 75% of the landiolol administered dose (approximately half of this as metabolite M1, and 8% as parent) is recovered in urine at four hours and 89 to 99% at 24 hours following a 60 min intravenous infusion.

Landiolol steady state volume of distribution is 0.4 L/kg.

Total body clearance of landiolol is 57 mL/kg/min following a 20-hour continuous landiolol infusion of 37.3 mcg/kg/min.

応用分野 · 1 件

説明Landiolol was launched as iv infusion for the treatment of tachyarrhythmia during surgery. This structurally related derivative of esmolol can be synthesized in 3 linear steps from 3-(4-hydroxyphenyl)propionic acid by successive esterification followed by alkylation of the phenol function with (2S)-glycidyltosylate and opening of the resulting epoxide by the appropriate amine. Landiolol is an ultra short acting PI-adrenergic blocker more cardioselective (βI/β2 = 255) than esmolol (βi/β2 = 32). It showed 6-8 times greater efficiency compared to esmolol in reducing isoproterenol-induced increase in heart rate and ventricular contraction in anesthetized dogs. In clinical trials, landiolol was effective against a variety of arrhythmias with efficacy seen in patients with atrial fibrillation, proxysmal supraventricular tachycardia, ventricular tachycardia and premature complexes. Landiolol produced a doserelated pharmacokinetic behavior, has a rapid onset of action (10 min.) and is rapidly hydrolyzed to inactive acidic metabolites by esterases after iv administration. This results in an ultra-short half-life (approx. 3 min.) and p-blocade, allowing rapid termination of the drug effect by termination of infusion if side effects occur. Hypertension was the most frequent adverse event and resolved in less than 30 min. after drug withdrawal.

上流・下流製品情報

上流原料

1398109-46-0N-(2-Aminoethyl)morpholine-4-carboxamide oxalate

下流製品

ランジオロール塩酸塩