4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide

• ChemBase编号: 441
• 分子式: C27H29N5O6S
• 平均质量: 551.61406
• 单一同位素质量: 551.18385467
• SMILES: S(=O)(=O)(Nc1nc(nc(OCCO)c1Oc1c(OC)cccc1)c1ncccn1)c1ccc(C(C)(C)C)cc1
• Canonical SMILES: OCCOc1nc(nc(c1Oc1ccccc1OC)NS(=O)(=O)c1ccc(cc1)C(C)(C)C)c1ncccn1
• InChI: InChI=1S/C27H29N5O6S/c1-27(2,3)18-10-12-19(13-11-18)39(34,35)32-23-22(38-21-9-6-5-8-20(21)36-4)26(37-17-16-33)31-25(30-23)24-28-14-7-15-29-24/h5-15,33H,16-17H2,1-4H3,(H,30,31,32)
• InChIKey: GJPICJJJRGTNOD-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide
• IUPAC传统名: @bosentan; bosentan
• 商标名: Tracleer
• 别名: Bosentan hydrate; bosentan; Bosentan; 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide; 4-(1,1-Dimethylethyl)-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)[2,2’-bipyrimidin]-4-yl]benzenesulfonamide; p-tert-Butyl-N-[6-(2-hydroxyethoxy)-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzenesulfonamide; Actelion; Ro 47-0203; Ro 47-0203/039; Tracleer; Bosentan hydrate

登记号

• CAS号: 147536-97-8; 157212-55-0
• MDL号: MFCD00867375
• PubChem SID: 160963904; 46507154
• PubChem CID: 104865

理论计算性质

JChem

• Acid pKa: 5.795967
• 质子受体: 9
• 质子供体: 2
• LogD (pH = 5.5): 4.7824826
• LogD (pH = 7.4): 3.976462
• Log P: 4.941747
• 摩尔折射率: 166.6572 cm^3
• 极化性: 56.402653 Å^3
• 极化表面积: 145.65 Å^2
• 可自由旋转的化学键: 10
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 4.18
• LOG S: -4.79
• 溶解度: 9.04e-03 g/l

分子性质

理化性质

• 溶解度: DMSO; Methanol; Poorly soluble in water (1.0 mg/100 ml) and in aqueous solutions at low pH (0.1 mg/100 ml at pH 1.1 and 4.0; 0.2 mg/100 ml at pH 5.0). Solubility increases at higher pH values (43 mg/100 ml at pH 7.5).
• 外观: Pale Yellow to Off-White Solid
• 熔点: 107-110°C
• 疏水性(logP): 3.7; 4.167

安全信息

• 保存条件: -20°C Freezer

药理学性质

• 作用靶点: Others

产品相关信息

• 纯度: 95%; 97%
• 成盐信息: Free Base

详细说明

DrugBank - DB00559

• Drug Groups: approved; investigational
• Description: Bosentan is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH). It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer®. Bosentan is used to treat pulmonary hypertension by blocking the action of endothelin molecules that would otherwise promote narrowing of the blood vessels and lead to high blood pressure.
• Indication: Used in the treatment of pulmonary arterial hypertension (PAH), to improve exercise ability and to decrease the rate of clinical worsening (in patients with WHO Class III or IV symptoms).
• Pharmacology: Bosentan belongs to a class of drugs known as endothelin receptor antagonists (ERAs). Patients with PAH have elevated levels of endothelin, a potent blood vessel constrictor, in their plasma and lung tissue. Bosentan blocks the binding of endothelin to its receptors, thereby negating endothelin's deleterious effects.
• Toxicity: Bosentan has been given as a single dose of up to 2400 mg in normal volunteers, or up to 2000 mg/day for 2 months in patients, without any major clinical consequences. The most common side effect was headache of mild to moderate intensity. In the cyclosporine A interaction study, in which doses of 500 and 1000 mg b.i.d. of bosentan were given concomitantly with cyclosporine A, trough plasma concentrations of bosentan increased 30-fold, resulting in severe headache, nausea, and vomiting, but no serious adverse events. Mild decreases in blood pressure and increases in heart rate were observed. There is no specific experience of overdosage with bosentan beyond the doses described above. Massive overdosage may result in pronounced hypotension requiring active cardiovascular support.
• Affected Organisms: Humans and other mammals
• Biotransformation: Bosentan is metabolized in the liver by the cytochrome P450 enzymes CYP2C9 and CYP3A4 (and possibly CYP2C19), producing three metabolites, one of which, Ro 48-5033, is pharmacologically active and may contribute 10 to 20% to the total activity of the parent compound.
• Absorption: Absolute bioavailability is approximately 50% and food does not affect absorption.
• Half Life: Terminal elimination half-life is about 5 hours in healthy adult subjects.
• Protein Binding: Greater than 98% to plasma proteins, mainly albumin.
• Elimination: Bosentan is eliminated by biliary excretion following metabolism in the liver.
• Distribution: * 18 L
• Clearance: * 4 L/h [patients with pulmonary arterial hypertension]
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - B675900

A mixed endothelin receptor antagonist. Used as a vasodilator. Antihypertensive.

参考文献

• Clozel, M., et al.: J. Pharmacol. Exp. Ther., 270, 228 (1994)
• Gutsch, G., et al.: Cardiovasc. Drugs Ther., 10, 717 (1994)
• Weber, C., et al.: Clin Pharmacol. Ther., 60, 124 (1994)
• Krum, H., et al.: N. Engl. J. Med., 338, 784 (1998)