Tenofovir Alafenamide
Tenofovir Alafenamide Basic information
- Product Name:
- Tenofovir Alafenamide
- Synonyms:
-
- Tenofovir Alafenamide fumarate, N-[[S(P)]-[2-(Adenin-9-yl)-1(R)-methylethoxymethyl](phenoxy)phosphoryl]-L-alanine isopropyl ester
- (S)-Isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate
- Tenofovir Alafenamide (GS-7340)
- GS-7340/GS7340
- GS-7340 Tenofovir alafenamide
- tenofovir alafenamide
- GS-7340-03
- L-Alanine, N-[(S)-[[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-, 1-methylethyl ester
- CAS:
- 379270-37-8
- MF:
- C21H29N6O5P
- MW:
- 476.47
- EINECS:
- 1592732-453-0
- Product Categories:
-
- Inhibitors
- Intermediate
- 379270-37-8
- Mol File:
- 379270-37-8.mol
Tenofovir Alafenamide Chemical Properties
- Melting point:
- >119°C (dec.)
- Boiling point:
- 640.4±65.0 °C(Predicted)
- Density
- 1.39±0.1 g/cm3(Predicted)
- storage temp.
- 2-8°C(protect from light)
- solubility
- Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
- pka
- 4.21±0.10(Predicted)
- form
- Solid
- color
- White to Off-White
- Stability:
- 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|
Tenofovir Alafenamide Usage And Synthesis
Description
Tenofovir Alafenamide (GS-7340) is a prodrug of tenofovir, which is a reverse transcriptase inhibitor, used to treat HIV and Hepatitis B.-Reverse Transcriptase inhibitor. It was developed by Gilead Sciences. Compared to tenofovir disoproxil fumarate, tenofovir alafenamide has a greater antiviral activity and better distribution into lymphoid tissues.
Description
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).
Uses
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.
Synthesis
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 AlafenamideSupplier
- Tel
- sales@boylechem.com
- Tel
- 0512-58900862 400-0707518
- sales@alabiochem.com
- Tel
- +86-21-20908456
- sales@BioChemBest.com
- Tel
- 010-89508211 18501085097
- sales.bj@hwrkchemical.com
- Tel
- 0311-89250318 031166536426
- master@sjzsdyn.com
Tenofovir Alafenamide(379270-37-8)Related Product Information
- Thionyl chloride
- D-Alanine Isopropyl Ester HCl
- 6N-HydroxyMethyl Tenofovir Disoproxil
- Tenofovir Related Compound 14
- Tenofovir Alafenamide PMPA Impurity
- Pimecrolimus
- 9-[(R)-2-(Phosphonomethoxy)propyl]adenine monohydrate
- Tenofovir disoproxil
- 9-Propenyladenine
- Tenofovir
- DNA, SINGLE STRANDED, IMM. ON CELLULOSE, FROM CALF THYMUS*
- diisopropyl 2,2'-((((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphoryl)bis(azanediyl))(2S,2'S)-dipropionate compound with methane (1:1)
- Tenofovir Related Compound 6
- Tenofovir disoproxil fumarate
- phenyl hydrogen ((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate
- Tenofovir alafenamide hemifumarate
- GS-7340 (fuMarate)
- Tenofovir Alafenamide Impurity 30