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TICAGRELOR Produkt Beschreibung

TICAGRELOR Struktur
274693-27-5
CAS-Nr.
274693-27-5
Englisch Name:
TICAGRELOR
Synonyma:
Ticag;Possia;CS-256;Tikagre;Brilinta;Ticagrel;Brilique;Azd 6140;Ticagrelo;Ticarelor
CBNumber:
CB51509134
Summenformel:
C23H28F2N6O4S
Molgewicht:
522.57
MOL-Datei:
274693-27-5.mol

TICAGRELOR Eigenschaften

Siedepunkt:
777.6±70.0 °C(Predicted)
Dichte
1.67
storage temp. 
Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
pka
13.26±0.70(Predicted)

Sicherheit

S-Sätze: 24/25
HS Code  29335990
Giftige Stoffe Daten 274693-27-5(Hazardous Substances Data)

TICAGRELOR Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung

In December 2010, the P2Y12 receptor antagonist ticagrelor (also known as AZD6140) was approved in Europe for the treatment of acute coronary syndrome (ACS), a condition that covers several clinical symptoms with the potential to cause acute myocardial ischemia (MI). ADP binds to two purinergic receptors, the P2Y1 and P2Y12 receptors. The action of ADP binding to the P2Y12 receptor results in activation of the GP Ⅱb/Ⅲa (integrin) receptor.GP Ⅱb/Ⅲa initiates and prolongs platelet aggregation, which in turn results in the cross-linking of platelets through fibrin and finally thrombus formation. Inhibition of ADP stimulation of the P2Y12 receptor has been found to be an effective strategy for managing the atherothrombotic events associated with ACS and potentially resulting from percutaneous coronary intervention (PCI, stent implantation) .

Chemische Eigenschaften

White Solid

Originator

Astra-Zeneca (United Kingdom)

Verwenden

Ticagrelor, the first reversible oral P2Y12 receptor antagonist, provides faster, greater, and more consistent ADP-receptor inhibition than Clopidogrel. Used in the treatment of acute coronary syndromes (ACS)

Verwenden

Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist, also inhibits CYP2C9 and 4-hydroxylation with IC50 of 10.5 μM and 8.2 μM respectively

Definition

ChEBI: A triazolopyrimidine that is an adenosine isostere; the cyclopentane ring is similar to ribose and the nitrogen-rich [1,2,3]triazolo[4,5-d]pyrimidine moiety resembles the nucleobase adenine. A platelet aggregation inhibitor which is used for p evention of thromboembolic events in patients with acute coronary syndrome.

Trademarks

Brilique and Possia in the European Union

Clinical Use

Ticagrelor, discovered and developed by AstraZeneca, is a platelet adenosine diphosphate (ADP) P2Y12 (P2T) reversible receptor antagonist approved in the E.U. in 2010 and launched in Germany and the UK in 2011 for the treatment of patients with acute coronary syndromes (ACS). It was approved in the U.S. and Canada in 2011 following successful clinical trial results in patients with ACS which showed it to be superior to preexisting drugs for reducing death due to vascular causes. Ticagrelor is an oral drug indicated for use in combination with acetylsalicylic acid (aspirin) for the prevention of atherothrombotic events in adult patients with ACS (unstable angina, non-ST elevation myocardial infarction (NSTEMI), or ST elevation myocardial infarction (STEMI)). Unlike its competitors prasugrel and clopidogrel, which require bioactivation, ticagrelor is not a prodrug and does not require in vivo activation. It has a rapid onset of action, relatively rapid reversibility, greater potency, and exhibits consistency in platelet inhibition. Following dosing, ticagrelor reaches Cmax in about 1.5 h, with formation of a major metabolite with equipotent intrinsic activity to the parent compound.

Chemical Synthesis

The initial discovery of the drug and SAR studies were published in 2007, including the initial discovery patent applications. Since then, a number of patents have been published with various improvements made for largescale synthesis of the drug. While the molecule has been synthesized using various modifications of the common intermediates, the large-scale preparation proceeds via a convergent strategy involving the coupling of three key intermediates as shown in the Scheme below.
   
   
Several routes to the synthesis of cyclopentyl amino alcohol 235 have been reported. Most of these routes are based on reaction of cyclopentene acetate 238 with the appropriate amine, which is commercially available. Interestingly, one route targeting deuterated ticagrelor used a nitroxide Diels–Alder reaction with cyclopentadiene to incorporate the amine into the ring system. The most likely process-scale preparation of the key cyclopentyl amine required for ticagrelor is highlighted in the scheme below.
image.png
Commercially available enantiopure acetate 238 was reacted with sodium di-tert-butyloxy diimide under catalytic palladiummediated amination conditions to give bis-Boc amide 239 in 92% yield. Dihydroxylation of cyclopentene 239 using catalytic osmium tetraoxide and N-methyl morpholine N-oxide (NMO) in THF/water quantatively resulted in the cis-diol 240. The free amine was liberated with 6 N HCl followed by in situ ketalizaion of the cis-diol hydrochloride salt 241 in 92% yield. Cbz carbamate 242 was quantitatively synthesized from 241 under standard conditions. Alcohol 242 was treated with potassium t-butoxide and bromoethyl acetate (243), the ester intermediate of which was reduced in situ with lithium borohydride to alcohol 244 in 86% overall yield (two steps). Hydrogenolysis at 1.2 bar of hydrogen pressure with 5% Pd/C gave amino alcohol intermediate 235 in 83% yield. This amine (235) was mixed with oxalic acid to provide the oxalate salt in 82% yield, which was subsequently used for the final synthesis of ticagrelor.
The large-scale preparation of ticagrelor necessitated the synthesis of dichloroamino pyrimidine thioether 236, for which there are several reported routes. The synthesis is initiated with the construction of thiol barbituric acid 247 (Scheme below). This intermediate was formed from the reaction of dimethyl malonate (245) with thiourea (246) in the presence of sodium methoxide. These conditions provided the sodium salt of the pyrimidone thiol 247 in 83% yield, which was isolated via filtration from the reaction mixture. Salt 247 was then reacted with propyliodide in aqueous methanolic sodium hydroxide followed by HCl quench to provide the desired thioether 248 in 76% yield. Nitration of pyrimidinol thioether 248 was achieved by treatment with fuming nitric acid in acetic acid, furnishing the nitro pyrimidinol 249 in 75% yield. Subsequent bis-chlorination with POCl3 converted 249 to dichloropyrimidine thioether 250 in near quantitative yield. In an earlier publication, a selective reduction of the nitro dichloropyrimide thioether 250 was demonstrated by hydrogenation at 3 bar hydrogen pressure using 3%Pt/0.6%V/C catalyst to provide the amino dichloropyrimidine thioether 236 in 95% yield. It is also of note that for the larger kilo-scale reaction, selective hydrogenation was accomplished with Pt/V/C (2% Pt; 1% V on carbon) catalyst with 8 bar of hydrogen pressure to give the crude amino dichloropyrimidine thioether 236.
image.png
While a number of routes have been described for the preparation of cyclopropyl amine intermediate 237,184–187,193–196

TICAGRELOR Upstream-Materialien And Downstream Produkte

Upstream-Materialien

Downstream Produkte


TICAGRELOR Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global( 456)Lieferanten
Firmenname Telefon Fax E-Mail Land Produktkatalog Edge Rate
Zhuozhou Wenxi import and Export Co., Ltd
+8613111626072 (WhatsApp)
Wechat: +8613111626072 Wickr me: waynehu zzwenxi@126.com CHINA 13187 58
Nanjing Gold Pharmaceutical Technology Co. Ltd.
025-84209270 15906146951
025-84209270 wgp@nanjing-pharmaceutical.com CHINA 115 55
Shanghai Yingrui Biopharma Co., Ltd.
+86-21-33585366 E-mail:sales03@shyrchem.com
+86-21-34979012 sales03@shyrchem.com CHINA 739 60
Beijing Cooperate Pharmaceutical Co.,Ltd
010-60279497
010-60279497 sales01@cooperate-pharm.com CHINA 1817 55
Casorganics US Corp
+17326109938
sales@casorganics.com CHINA 175 58
Echemi Group
18905328650 86-18905328650
pharma@echemi.com CHINA 215 58
Shanghai UCHEM Inc.
15502138767 15502138767
sales@myuchem.com CHINA 2773 58
Shenzhen Shengda Pharma Limited
+86-755-85269922
WeChat:shengdapharm sales@shengdapharm.com CHINA 304 58
AFINE CHEMICALS LIMITED
008657185134551
008657185134895 info@afinechem.com CHINA 15559 58
Capot Chemical Co.,Ltd.
+86(0)13336195806 +86-571-85586718
+86-571-85864795 sales@capotchem.com China 20012 60

274693-27-5()Verwandte Suche:


  • 1,2-Cyclopentanediol, 3-[7-[[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-, (1S,2S,3R,5S)-
  • Ticagrelor, >=98%
  • Ticagrelo
  • Ticargrelor
  • Brilinta
  • Possia
  • Ticagrelor and intermediates
  • Ticagrelor Standards
  • Ticarelor
  • (1S,2S,3R,5S)-3-(7-(((1R,2S)-2-(4-fluoro-3-(methylthio)phenyl) cyclopropyl)amino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol
  • AZ13265501
  • Tikagre
  • Ticagrel
  • Ticagrelor Impurity 81
  • Ticagrelor (Brilinta,AZD6140)
  • CS-256
  • AZD-6140; TICAGRELOR ; BRILINTA; AZD 6140
  • 1,2,3]triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1,2-diol
  • Ticagrelor standard
  • Brilique
  • (1S,2S,3R,5S)-3-[7-[[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino]-5-propylsulfanyltriazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1,2-diol
  • TICAGRELOR
  • (1S,2S,3R,5S)-3-[7-[[(1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)-1,2-cyclopentanediol
  • Azd 6140
  • Unii-glh0314rvc
  • (1S,2S,3R,5S)-3-(7-(((1S,2S)-2-(3,4-difluorophenyl)cyclopropyl)aMino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyriMidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol
  • AR-C 126532XX
  • Ticagrelor(AR-C 126532XX
  • Ticagrelor (AZD6140)
  • (1S,2S,3R,5S)-3-(7-((1R,2S)-2-(3,4-difluorophenyl)cyclopropylaMino)-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyriMidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol
  • (1S,2S,3R,5S)-3-[7-[[(1R,2S)-2-(3,4-D1,2-Cyclopentanediolifluorophenyl)cyclopropyl]aMino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyriMidin-3-yl]-5-(2-hydroxyethoxy)-1,2-cyclopentanediol
  • 3-[7-[[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]aMino]-5-(propylthio)-3H-1,2,3-triazolo[4,5-d]pyriMidin-3-yl]-5-(2-hydroxyethoxy)-,(1S,2S,3R,5S)-
  • Tecagrelor
  • (1S,2S,3R,5S)-3-[7-[(1R,2S)-2-(3,4-Difluorophenyl)cyclopropylaMino]-5-(propylsulfanyl)-3H-[1,2,3]triazolo[4,5-d]pyriMidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1,2-diol
  • Ticag
  • AR-C 126532XX fandachem
  • TICAGRELOR fandachem
  • (1S,2S,3R,5S)-3-(7-(((1R)-2-(3,4-Difluorophenyl)cyclopropyl)amino)-5-(propylthio)-3h-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl)-5-(2-hydroxyethoxy)cyclopentane-1,2-diol
  • icagrelor
  • TICAGRELOR USP/EP/BP
  • Ticagrelore
  • Ticagrelor Form Ⅱ
  • 274693-27-5
  • 374693-27-5
  • 74693-27-5
  • C23H28F2N6O4S
  • AZD6140
  • Ticagrelor
  • Cardiovascular APIs
  • Aromatics
  • Heterocycles
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • Sulfur & Selenium Compounds
  • API
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