ChemicalBook > CAS DataBase List > Ambrisentan

Ambrisentan

Product Name
Ambrisentan
CAS No.
177036-94-1
Chemical Name
Ambrisentan
Synonyms
CS-135;LU 208075;BSF 208075;AMBRISENTAN;Anrisentan API;((S)-Ambrisentan);(R,S)-Ambrisentan;Ambrisentan, >=98%;Ambrisentan Tablets;(R,S)-AMbrisentan-d5
CBNumber
CB71011125
Molecular Formula
C22H22N2O4
Formula Weight
378.42
MOL File
177036-94-1.mol
More
Less

Ambrisentan Property

Melting point:
>150°C (dec.)
Boiling point:
551.1±60.0 °C(Predicted)
Density 
1.228±0.06 g/cm3(Predicted)
storage temp. 
Sealed in dry,2-8°C
solubility 
DMSO (Slightly), Methanol (Slightly)
form 
Solid
pka
0.97±0.10(Predicted)
color 
White to Off-White
Merck 
14,384
InChI
InChI=1S/C22H22N2O4/c1-15-14-16(2)24-21(23-15)28-19(20(25)26)22(27-3,17-10-6-4-7-11-17)18-12-8-5-9-13-18/h4-14,19H,1-3H3,(H,25,26)
InChIKey
OUJTZYPIHDYQMC-UHFFFAOYSA-N
SMILES
C(OC1N=C(C)C=C(C)N=1)(C(O)=O)C(OC)(C1=CC=CC=C1)C1=CC=CC=C1
More
Less

Safety

Risk Statements 
62/63
Safety Statements 
53-36/37/39-45
RTECS 
UA2459660
HS Code 
29335990
More
Less

Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal word
Danger
Precautionary statements

P201Obtain special instructions before use.

P308+P313IF exposed or concerned: Get medical advice/attention.

More
Less

N-Bromosuccinimide Price

Sigma-Aldrich
Product number
SML2104
Product name
Ambrisentan
Purity
≥98% (HPLC)
Packaging
10MG
Price
$128
Updated
2023/06/20
Sigma-Aldrich
Product number
SML2104
Product name
Ambrisentan
Purity
≥98% (HPLC)
Packaging
50MG
Price
$517
Updated
2023/06/20
TCI Chemical
Product number
A2966
Product name
Ambrisentan
Purity
>98.0%(HPLC)
Packaging
20mg
Price
$29
Updated
2024/03/01
TCI Chemical
Product number
A2966
Product name
Ambrisentan
Purity
>98.0%(HPLC)
Packaging
100mg
Price
$83
Updated
2024/03/01
Cayman Chemical
Product number
23669
Product name
Ambrisentan
Purity
≥98%
Packaging
1mg
Price
$32
Updated
2024/03/01
More
Less

Ambrisentan Chemical Properties,Usage,Production

Description

Ambrisentan is a selective endothelin-A (ETA) receptor antagonist introduced for the oral treatment of patients with pulmonary arterial hypertension (PAH), to improve exercise capacity and delay clinical worsening. It is the third ET-receptor antagonist to be marketed for this indication behind bosentan and sitaxsentan. PAH is a rare disease of the small pulmonary arteries characterized by vascular proliferation and remodeling, resulting in a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, and ultimately, right ventricular failure and premature death. Early symptoms of PAH include gradual onset of shortness of breath, fatigue, palpitation, edema, and fainting. Endothelin-1 (ET-1), a potent vasoconstrictor and smooth muscle mitogen, is a key contributor to the acceleration of the disease, and its effects are mediated through activation ofETA and ETB receptors.

Description

Ambrisentan is a nonpeptide endothelin A (ETA) receptor antagonist (IC50s = 0.251, 0.316, 0.398, 251, and 630 nM for rat preparations of heart, bladder, kidney, lung, and cerebral cortex, respectively). It inhibits contraction of isolated rabbit aortic rings induced by endothelin-1 (ET-1; ) by 43.23% when used at a concentration of 1 μM. Ambrisentan inhibits ET-1-induced contraction of human pulmonary and radial arteries in vitro (Kd = 0.042 and 0.11 μM, respectively). In a rat model of neonatal hyperoxic lung injury, ambrisentan (20 mg/kg per day, s.c.) reduces pulmonary arterial hypertension (PAH) as well as decreases PAH-induced right ventricular hypertrophy (RVH) and peak RV pressure. Formulations containing ambrisentan have been used to treat PAH.

Chemical Properties

White to Off White Solid

Originator

Abbott (US)

Uses

Nonpeptide endothelin ETA receptor antagonist. Antihypertensive

Uses

antihypertensive;endothelin receptor antagonist

Definition

ChEBI: Ambrisentan is a diarylmethane.

brand name

Letairis

General Description

Ambrisentan, (+)-(2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropanoic acid(Letairis), is a potent ETA selective endothelin antagonist that,is indicated, in the treatment of pulmonary arterial hypertension(PAH). PAH is a rare disease that if left untreated has ahigh mortality rate. In June of 2007, the FDA granted approvalof ambrisentan for once-daily treatment of PAH.Studies have shown that it improves a 6-minute walk by about30 to 60 m for patients receiving placebo.

Clinical Use

Endothelin A (ETA) receptor antagonist:
Treatment of pulmonary arterial hypertension

Synthesis

Both the discovery and process routes to the synthesis of ambrisentan have been published and the process route is described as shown in the scheme. Reacting a mixture of benzophenone (14) and sodium methoxide in THF at 0??C with methylchloroacetate over a four hour period provided glycidate 15 which was taken forward without purification to the subsequent step. Addition of ptoluenesulfonic acid monohydrate to a solution of glycidate 15 in methanol was followed by heating at reflux and distilling out the solvent until the temperature reached 66??C. While the solution was still refluxing, 10% potassium hydroxide was added and the remaining organic solvent was distilled out until the temperature reached 94??C, providing complete hydrolysis to acid 16. The reaction was cooled to room temperature and diluted with water and methyl tert-butylether (MTBE) then acidified with 10% sulfuric acid. The MTBE layer was separated and taken to the next step. Additional MTBE and methanol were added to the crude acid 17 and the resulting mixture was heated at reflux. (S)-1-(4-chlorophenyl) ethylamine was added to the refluxing solution and the resulting mixture was allowed to cool to 0-5??C slowly at a rate of 10??C/h which resulted in crystallization of the salt 19 in 33% overall yield from benzophenone and 99% e.e. The chiral hydroxyl acid salt 19 was mixed with sulfone 20 and lithium amide in a toluene/DMF mixture and heated at 45??C for 12 hours to give, after acidic workup and crystallization, ambrisentan (II) in 84% yield as a colorless powder with 99.8% e.e.

Drug interactions

Potentially hazardous interactions with other drugs
Ciclosporin: concentration of ambrisentan doubled with an increased risk of side effects; maximum dose 5 mg daily.

Metabolism

Ambrisentan is glucuronidated via several UGT isoenzymes (UGT1A9S, UGT2B7S and UGT1A3S) to form ambrisentan glucuronide (13%). Ambrisentan also undergoes oxidative metabolism mainly by CYP3A4 and to a lesser extent by CYP3A5 and CYP2C19 to form 4-hydroxymethyl ambrisentan (which has little activity) which is further glucuronidated to 4-hydroxymethyl ambrisentan glucuronide.
Ambrisentan is excreted mainly by the liver, although the contribution of hepatic metabolism and biliary excretion is unknown.

storage

Store at +4°C

References

[1] vatter h, seifert v. ambrisentan, a non-peptide endothelin receptor antagonist. cardiovascular drug reviews, 2006, 24(1): 63-76.
[2] barst r j. a review of pulmonary arterial hypertension: role of ambrisentan. vascular health and risk management, 2007, 3(1): 11.

Ambrisentan Preparation Products And Raw materials

Raw materials

Preparation Products

More
Less

Ambrisentan Suppliers

Jinan Cheminn Chemicals Co., Ltd.
Tel
531-67875205 15726170169
Fax
+86-531-67875205
Email
sales@cheminn.com
Country
China
ProdList
60
Advantage
60
Chengdu Aslee Biopharmaceuticals, Inc
Tel
028-85305008 02885305008
Fax
4000210878-186
Email
2306208234@qq.com
Country
China
ProdList
1005
Advantage
50
Shanghai Boyle Chemical Co., Ltd.
Tel
Fax
86-21-57758967
Email
sales@boylechem.com
Country
China
ProdList
2922
Advantage
55
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Fax
86-10-82849933
Email
jkinfo@jkchemical.com
Country
China
ProdList
96815
Advantage
76
Chembest Research Laboratories Limited
Tel
+86-21-20908456
Fax
021-58180499
Email
sales@BioChemBest.com
Country
China
ProdList
6005
Advantage
61
Capot Chemical Co., Ltd
Tel
+86 (0) 571 85 58 67 18
Fax
0086-571-85864795
Email
sales@capotchem.com
Country
China
ProdList
18207
Advantage
66
Shanghai Scientia Pharmaceutical Technology Co., Ltd.
Tel
21-21-54301573 13917723525
Fax
(86)21-51861981
Email
sales@scientiapharm.com
Country
China
ProdList
263
Advantage
62
Jia Xing Isenchem Co.,Ltd
Tel
0573-85285100 18627885956
Fax
0573-85285100
Email
isenchem@163.com
Country
China
ProdList
9414
Advantage
66
Adamas Reagent, Ltd.
Tel
400-6009262 16621234537
Fax
021-64823266
Email
chenyj@titansci.com
Country
China
ProdList
14103
Advantage
59
LGM Pharma
Tel
1-(800)-881-8210
Fax
615-250-9817
Email
inquiries@lgmpharma.com
Country
United States
ProdList
2123
Advantage
70
More
Less

View Lastest Price from Ambrisentan manufacturers

WUHAN FORTUNA CHEMICAL CO., LTD
Product
Ambrisentan 177036-94-1
Price
US $0.00/KG
Min. Order
1KG
Purity
99%min
Supply Ability
100kg
Release date
2021-11-20
BEIJING SJAR TECHNOLOGY DEVELOPMENT CO., LTD.
Product
Ambrisentan 177036-94-1
Price
US $0.00/g
Min. Order
1g
Purity
More Than 99%
Supply Ability
100kg/Month
Release date
2024-10-11
Baoji Guokang Bio-Technology Co., Ltd.
Product
Ambrisentan 177036-94-1
Price
US $254.00/g/Bag
Min. Order
10KG
Purity
99%
Supply Ability
10kg
Release date
2021-06-22

177036-94-1, AmbrisentanRelated Search:


  • BSF 208075,(+)-(2S)-2-[(4,6-DIMETHYLPYRIMIDIN-2-YL)OXY]-3-METHOXY-3,3-DIPHENYLPROPANOIC ACID
  • AMBRISENTAN
  • (aS)-a-[(4,6-Dimethyl-2-pyrimidinyl)oxy]--methoxy--phenylbenzenepropanoic Acid
  • BSF 208075
  • LU 208075
  • 2-(4,6-Dimethylpyrimidin-2-yl)oxy-3-methoxy-3,3-di(phenyl)propanoic acid
  • (S)-2-(4,6-dimethylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropanoic acid
  • (+-)-(2S)-2-((4,6-Dimethylpyrimidin-2-yl)oxy)-3-methoxy-3,3-diphenylpropanoic acid,bsf-208075
  • Ambrisentan Tablets
  • Benzenepropanoic acid, α-[(4,6-diMethyl-2-pyriMidinyl)oxy]-β-Methoxy-β-phenyl-, (αS)-
  • Benzenepropanoic acid, alpha-[(4,6-diMethyl-2-pyriMidinyl)oxy]-beta-Methoxy-beta-phenyl-, (alphaS)-
  • (αS)-α-[(4,6-DiMethyl-2-pyriMidinyl)oxy]-β-Methoxy-β-phenylbenzenepropanoic Acid
  • (R,S)-AMbrisentan-d5
  • AMbrisentan (BSF 208075)
  • Benzenepropanoic acid, a-[(4,6-diMethyl-2-pyriMidinyl)oxy]-b-Methoxy-b-phenyl-, (aS)-
  • LU-208075,BSF-208075
  • Ambrisentan,2-(4,6-Dimethylpyrimidin-2-yl)oxy-3-methoxy-3,3-di(phenyl)propanoic acid
  • Ambrisentan, >=98%
  • (2S)-2-(4,6-dimethylpyrimidin-2-yl)oxy-3-methoxy-3,3-diphenylpropanoic acid
  • ambrisentan,CID 6918493
  • CS-135
  • Anrisentan API
  • (S)-2-[(4,6-Dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropionic Acid
  • Ambrisentan USP/EP/BP
  • ((S)-Ambrisentan)
  • AmbrisentanQ: What is Ambrisentan Q: What is the CAS Number of Ambrisentan Q: What is the storage condition of Ambrisentan Q: What are the applications of Ambrisentan
  • Ambelsentan intermediate
  • (2S)-2-(4,6-dimethylpyrimidin-2-yl)oxy-3-methoxy-3,3-diphenylpropanoicaci
  • Ambrisentan 98% 177036-94-1
  • Ambrisentan AKSci B500
  • (R,S)-Ambrisentan
  • Benzenepropanoic acid, α-[(4,6-dimethyl-2-pyrimidinyl)oxy]-β-methoxy-β-phenyl-, (αS)-
  • 177036-94-1
  • APIs
  • Aromatics
  • Heterocycles
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Other APIs