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

• ChemBase ID: 441
• Molecular Formular: C27H29N5O6S
• Molecular Mass: 551.61406
• Monoisotopic Mass: 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl]benzene-1-sulfonamide
• IUPAC Traditional name: @bosentan; bosentan
• Brand Name: Tracleer
• Synonyms: 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

Database IDs

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

CALCULATED PROPERTIES

JChem

• Acid pKa: 5.795967
• H Acceptors: 9
• H Donor: 2
• LogD (pH = 5.5): 4.7824826
• LogD (pH = 7.4): 3.976462
• Log P: 4.941747
• Molar Refractivity: 166.6572 cm^3
• Polarizability: 56.402653 Å^3
• Polar Surface Area: 145.65 Å^2
• Rotatable Bonds: 10
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 4.18
• LOG S: -4.79
• Solubility (Water): 9.04e-03 g/l

PROPERTIES

Physical Property

• Solubility: 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).
• Apperance: Pale Yellow to Off-White Solid
• Melting Point: 107-110°C
• Hydrophobicity(logP): 3.7; 4.167

Safety Information

• Storage Condition: -20°C Freezer

Pharmacology Properties

• Target: Others

Product Information

• Purity: 95%; 97%
• Salt Data: Free Base

DETAILS

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.

REFERENCES

• 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)