Tenofovir Alafenamide Struktur

Tenofovir Alafenamide

Bezeichnung:Tenofovir Alafenamide

CAS-Nr379270-37-8

Englisch Name:Tenofovir Alafenamide

CBNumberCB92627921

SummenformelC21H29N6O5P

Molgewicht476.47

MOL-Datei379270-37-8.mol

Tenofovir Alafenamide physikalisch-chemischer Eigenschaften

Schmelzpunkt	>119°C (dec.)
Siedepunkt	640.4±65.0 °C(Predicted)
Dichte	1.39±0.1 g/cm3(Predicted)
storage temp.	2-8°C(protect from light)
Löslichkeit	Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
pka	4.21±0.10(Predicted)
Aggregatzustand	Solid
Farbe	White to Off-White
Stabilität	Hygroscopic
InChIKey	LDEKQSIMHVQZJK-QTJFZWIYNA-N
SMILES	C(OC(C)C)(=O)[C@H](C)NP(CO[C@H](C)CN1C2=C(N=C1)C(N)=NC=N2)(OC1=CC=CC=C1)=O \|&1:6,12,r\|

Gefahreninformationscode (GHS)

Bildanzeige (GHS)
Alarmwort

Achtung
Gefahrenhinweise

H315：Verursacht Hautreizungen.

H318：Verursacht schwere Augenschäden.

H335：Kann die Atemwege reizen.
Sicherheit

P261：Einatmen von Staub vermeiden.

P264：Nach Gebrauch gründlich waschen.

P264：Nach Gebrauch gründlich waschen.

P271：Nur im Freien oder in gut belüfteten Räumen verwenden.

P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

P302+P352：BEI BERÜHRUNG MIT DER HAUT: Mit viel Wasser/... (Hersteller kann, falls zweckmäßig, ein Reinigungsmittel angeben oder, wenn Wasser eindeutig ungeeignet ist, ein alternatives Mittel empfehlen) waschen.

P304+P340：BEI EINATMEN: Die Person an die frische Luft bringen und für ungehinderte Atmung sorgen.

P305+P351+P338：BEI KONTAKT MIT DEN AUGEN: Einige Minuten lang behutsam mit Wasser spülen. Eventuell vorhandene Kontaktlinsen nach Möglichkeit entfernen. Weiter spülen.

P310：Sofort GIFTINFORMATIONSZENTRUM/Arzt/ anrufen.

P321：Besondere Behandlung

P332+P313：Bei Hautreizung: Ärztlichen Rat einholen/ärztliche Hilfe hinzuziehen.

P403+P233：An einem gut belüfteten Ort aufbewahren. Behälter dicht verschlossen halten.

P405：Unter Verschluss aufbewahren.

P501：Inhalt/Behälter ... (Entsorgungsvorschriften vom Hersteller anzugeben) zuführen.

Tenofovir Alafenamide Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Tenofovir alafenamide fumarate is an oral phosphonoamidate prodrug of the reverse transcriptase inhibitor tenofovir. It was approved by the USFDA for the treatment of chronic hepatitis B virus infection with compensated liver disease. Tenofovir alafenamide fumarate was discovered and developed by Gilead as a potentially safer form of the previously approved tenofovir disoproxil fumarate (Viread).
Verwenden
Tenofovir Alafenamide, also known as Tenofovir Impurity 51, is a prodrug of Tenofovir (T018500), which is a reverse transcriptase inhibitor used to treat HIV and Hepatitis B.
Definition
ChEBI: An L-alanine derivative that is isopropyl L-alaninate in which one of the amino hydrogens is replaced by an (S)-({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)( henoxy)phosphoryl group. A prodrug for tenofovir, it is used (as the fumarate salt) in combination therapy for the treatment of HIV-1 infection.
Synthese
A multikilogram synthesis of tenofovir alafenamide fumarate was described in a Gilead patent. Additional process improvements on specific steps of the Gilead process have been reported on 100 g scale, and these will be noted throughout the description of the synthesis. The synthesis was initiated with the alkylation of adenine (72) with (R)-propylene carbonate (73) to give hydroxypropyl adenine 74 in 75% yield. It should be noted that sodium hydroxide can be replaced by potassium bases with increased yields on 100 g scale.27 Alkylation of 74 with diethyl p-toluenesulfonyloxymethylphosphonate (75) gave intermediate 76, which was not isolated. Hydrolysis of the phosphonate esters with trimethylsilyl bromide followed by recrystallization from water gave phosphonic acid 77 in 50% yield. Interestingly, replacing Mg(Ot-Bu)2 with PhMgCl/t-BuOH led to improved yields for the alkylation step (74 ?ú 76) on a 100 g scale. Additionally, the authors note that conditions for hydrolyzing the phosphonate ester can be modified using HCl or HBr for improved yields on smaller scale. Dicyclohexylcarbodiimide (DCC) coupling of 77 with phenol produced phosphonate 78 in 51% yield. This step was also reported to proceed in higher yield on smaller scale by changing the solvent to cyclopentylmethyl ether. Monophosphonate ester 78 was treated with thionyl chloride followed by L-alanine isopropyl ester (79) and triethylamine to give tenofovir alafenamide rac-80 as a mixture of phosphonate diastereomers in 47% yield. The diastereomers were separated using simulated moving bed chromatography to give the desired diastereomer ent-80 in 47% yield and 99% diastereomeric purity. The diastereomers could also be separated using a crystallization-induced dynamic resolution of rac-80. Tenofovir alafenamide fumarate (VI) was prepared from ent-80 and fumaric acid in 83% yield.

Tenofovir Alafenamide Upstream-Materialien And Downstream Produkte

Tenofovir Alafenamide Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

379270-37-8, Tenofovir Alafenamide Verwandte Suche:

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