CAS 147536-97-8|Bosentan

Introduction：Basic information about CAS 147536-97-8|Bosentan, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Bosentan BiologicalActivity
3. Chemical & Physical Properties
4. Safety Information
5. Customs
6. Synonyms

Common Name	Bosentan
CAS Number	147536-97-8	Molecular Weight	551.614
Density	1.3±0.1 g/cm3	Boiling Point	742.3±70.0 °C at 760 mmHg
Molecular Formula	C₂₇H₂₉N₅O₆S	Melting Point	171-175 °C(lit.)
MSDS	/	Flash Point	402.8±35.7 °C

Names

Name	bosentan
Synonym	More Synonyms

Bosentan BiologicalActivity

Description	Bosentan is a competitive and dual antagonist of endothelin-1 (ET) for the ETA and ETB receptors with Ki of 4.7 nM and 95 nM in human SMC, respectively.
Related Catalog	Signaling Pathways >>GPCR/G Protein >>Endothelin ReceptorResearch Areas >>Cardiovascular Disease
Target	Ki: 4.7 nM (ETA receptor, in human SMC), 95 nM (ETA receptor, in human SMC)[1]
In Vitro	Bosentan (BOS) competitively and specifically antagonizes binding of 125I-labelled ET-1 to ETA receptors on human smooth muscle cells (SMC) and ETB receptors on human placenta cells. The in vitro binding affinity of Bosentan to ETA receptors on human SMC is 4.7 nM and to ETB receptors on human SMC or placenta cells is 41 or 95 nM. Bosentan has 67-fold greater selectivity for ETA than ETB receptors (mean IC50=7.1 vs 474.8 nM) in an in vitro 125I-labeling assay[1].
In Vivo	Single-dose Bosentan 62.5 mg significantly (p<0.01 vs baseline) plasma ET-1 levels by 2-fold in 7 pts with WHO class II or III idiopathic or CTD-associated PAH, with peak levels achieved at 8 h[1]. In hypertensive rats, Macitentan 30 mg/kg further decreases mean arterial blood pressure (MAP) by 19 mm Hg when given on top of Bosentan 100 mg/kg. Conversely, Bosentan given on top of Macitentan fails to induce an additional MAP decrease. In pulmonary hypertensive rats, Macitentan 30 mg/kg further decreases mean pulmonary artery pressure (MPAP) by 4 mm Hg on top of Bosentan, whereas a maximal effective dose of Bosentan given on top of Macitentan does not cause any additional MPAP decrease[3].
Cell Assay	Cell viability is evaluated by the trypan blue exclusion test. Human dermal fibroblasts are treated with the indicated concentration of Bosentan (10, 20 and 40 μM). Cell viability is examined at 24 and 48 hours. Stained (dead) and unstained (viable) cells are counted with a hematocytometer[2].
Animal Admin	Rats[3] Two-month-old DSS rats and two-month-old Wistar rats are used. Pharmacological effects on mean arterial pressure (MAP) or mean pulmonary arterial pressure (MPAP) and heart rate (HR) are measured up to 120 h after a single gavage at doses ranging from 0.1 to 100 mg/kg (Macitentan) or 3 to 600 mg/kg (Bosentan). To determine whether Macitentan can provide superior pharmacological activity vs. Bosentan, a study is designed in which: 1) Macitentan is administered on top of the maximal effective dose of Bosentan established by the dose-response curve. 2) the same dose of Bosentan is administered on top of the maximal effective dose of Macitentan. The maximal effective dose of the second compound is administered at Tmax of the first tested compound.
References	[1]. Dhillon S, et al. Bosentan: a review of its use in the management of mildly symptomatic pulmonary arterial hypertension. Am J Cardiovasc Drugs. 2009;9(5):331-50. [2]. Akamata K, et al. Bosentan reverses the pro-fibrotic phenotype of systemic sclerosis dermal fibroblasts via increasing DNA binding ability of transcription factor Fli1. Arthritis Res Ther. 2014 Apr 3;16(2):R86. [3]. Iglarz M, et al. Comparison of pharmacological activity of macitentan and bosentan in preclinical models of systemic and pulmonary hypertension. Life Sci. 2014 Nov 24;118(2):333-9. [4]. Son GY, et al. Endothelin Regulates Porphyromonas gingivalis-Induced Production of Inflammatory Cytokines. PLoS One. 2016 Dec 28;11(12):e0167713.

Chemical & Physical Properties

Density	1.3±0.1 g/cm3
Boiling Point	742.3±70.0 °C at 760 mmHg
Melting Point	171-175 °C(lit.)
Molecular Formula	C₂₇H₂₉N₅O₆S
Molecular Weight	551.614
Flash Point	402.8±35.7 °C
Exact Mass	551.183838
PSA	154.03000
LogP	1.15
Vapour Pressure	0.0±2.6 mmHg at 25°C
Index of Refraction	1.607
InChIKey	GJPICJJJRGTNOD-UHFFFAOYSA-N
SMILES	COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(-c2ncccn2)nc1OCCO
Storage condition	-20°C Freezer

Safety Information

Hazard Codes	Xi
Risk Phrases	R36:Irritating to the eyes. R43:May cause sensitization by skin contact.
Safety Phrases	S26-S36/37-S24/25-S22
WGK Germany	3
HS Code	2935009090

Customs

HS Code	2935009090
Summary	2935009090 other sulphonamides VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:35.0%

Synonyms

4-tert-Butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl]benzenesulfonamide

MFCD00867375

Benzenesulfonamide, 4-(1,1-dimethylethyl)-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)[2,2'-bipyrimidin]-4-yl]-

Bosentan

Actelion

ro47-0203

ro47-0203/039

4-(1,1-Dimethylethyl)-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)[2,2'-bipyrimidin]-4-yl]benzenesulfonamide

N-[6-(2-Hydroxyethoxy)-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl]-4-(2-methyl-2-propanyl)benzenesulfonamide

UNII-XUL93R30K2

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