Sofosbuvir
- Iupac Name：propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
- CAS No.: 1190307-88-0
- Molecular Weight：529.45300
- Modify Date.: 2022-11-25 01:13
- Introduction: Sofosbuvir is a drug used for the treatment of hepatitis C. It is recommended to be used in combination with other drugs (such as velpatasvir) for the first-line treatment for HCV genotypes 1, 2, 3, 4, 5, and 6. It takes effect through acting as a nucleotide analog inhibitor, being capable of specially inhibiting the HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase.
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1. Names and Identifiers
- 1.1 Name
- Sofosbuvir
- 1.2 Synonyms
GS 7977 Hepcinat Hepcvir Isopropyl (2S)-2-[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydrofuran-2-yl]methoxy-phenoxy-phosphoryl]amino]propionate L-Alanine, N-[[P(S),2′R]-2′-deoxy-2′-fluoro-2′-methyl-P-phenyl-5′-uridylyl]-, 1-methylethyl ester PSI 7977 Resof Sovaldi Sovihep
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- 1.3 CAS No.
- 1190307-88-0
- 1.4 CID
- 45375808
- 1.5 EINECS(EC#)
- 11-000-0
- 1.6 Molecular Formula
- C22H29FN3O9P (isomer)
- 1.7 Inchi
- InChI=1S/C22H29FN3O9P/c1-13(2)33-19(29)14(3)25-36(31,35-15-8-6-5-7-9-15)32-12-16-18(28)22(4,23)20(34-16)26-11-10-17(27)24-21(26)30/h5-11,13-14,16,18,20,28H,12H2,1-4H3,(H,25,31)(H,24,27,30)/t14-,16+,18+,20+,22+,36-/m0/s1
- 1.8 InChIkey
- TTZHDVOVKQGIBA-IQWMDFIBSA-N
- 1.9 Canonical Smiles
- CC(C)OC(=O)C(C)NP(=O)(OCC1C(C(C(O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3
- 1.10 Isomers Smiles
- C[C@@H](C(=O)OC(C)C)N[P@](=O)(OC[C@@H]1[C@H]([C@@]([C@@H](O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3
2. Properties
- 2.1 Density
- 1.41
- 2.1 Melting point
- 120-125°C
- 2.1 Refractive index
- 1.573
- 2.1 Precise Quality
- 529.16300
- 2.1 PSA
- 167.99000
- 2.1 logP
- 2.04740
- 2.1 Solubility
- In water, 105 mg/L at 25 °C (est)
- 2.2 Decomposition
- Thermal decomposition may produce toxic gases such as carbon monoxide, carbon dioxide, and nitrogen oxides.
- 2.3 pKa
- 9.39±0.10(Predicted)
- 2.4 Water Solubility
- In water, 105 mg/L at 25 °C (est)
- 2.5 Stability
- Stable if stored as directed; avoid strong oxidizing agents
3. Use and Manufacturing
- 3.1 Definition
- ChEBI: A nucleotide conjugate that is used in combination with ledipasvir (under the trade name Harvoni) for the treatment of chronic hepatitis C genotype 1 infection.
- 3.2 Methods of Manufacturing
- General procedure: To a solution of General procedure: To a solution of General procedure: To a solution of General procedure: To a solution of To a solution of Sofosbuvir (529 mg, 1.0 mmol, 1.0 eq.) in 5 mL DMFcooled in an ice bath was added imidazole (204 mg, 3.0 mmol, 3.0 eq.)and triethylsilyl chloride (301 mg, 2.0 mmol, 2.0 eq.). After stirring for3 h, the reaction mixture was poured into water (50 mL) and extractedwith EA (10 mL×3). The organic layer was washed with water, driedover anhydrous Na2SO4 and purified by silica gel chromatography toafford 5 as a white solid. Yield: 86.5%. 1H NMR (500 MHz, DMSO): delta11.54 (s, 1H), 7.63 (d, 1H, J=8.0 Hz), 7.37 (t, 2H, J=8.0 Hz), 7.17-7.22 (m, 3H), 6.12 (dd, 1H, J=12.5 Hz, 10.5 Hz), 6.10 (d, 1H, J=19.0 Hz), 5.63 (dd, 1H, J=8.0 Hz, 2.0 Hz), 4.85 (sep, 1H, J=6.0 Hz), 4.33-4.36 (m, 1H), 4.17-4.21 (m, 1H), 3.97-4.12 (m, 2H), 3.75-3.83 (m, 1H), 1.27 (d, 3H, J=22.5 Hz), 1.23 (d, 3H, J=7.0 Hz), 1.15 (d, 3H, J=1.5 Hz), 1.14 (d, 3H, J=1.5 Hz), 0.93 (t, 9H, J=8.0 Hz), 0.63 (q, 6H, J=8.0 Hz). ESI+-MS m/z: 644.5 [M+1].
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- 3.3 Usage
- PSI-7977 is a phosphoramidate prodrug of PSI-7851, a nucleoside analog that, when phosphorylated, inhibits the RNA-dependent RNA polymerase of hepatitis C virus (EC50 = 92 nM). PSI-7977 is effective in vitro and in vivo.[Cayman Chemical]
4. MSDS
2.Hazard identification
2.1 Classification of the substance or mixture
Specific target organ toxicity \u2013 repeated exposure, Category 2
2.2 GHS label elements, including precautionary statements
| Pictogram(s) |  |
| Signal word | Warning |
| Hazard statement(s) | H373 May cause damage to organs through prolonged or repeated exposure |
| Precautionary statement(s) | |
| Prevention | P260 Do not breathe dust/fume/gas/mist/vapours/spray. |
| Response | P314 Get medical advice/attention if you feel unwell. |
| Storage | none |
| Disposal | P501 Dispose of contents/container to ... |
2.3 Other hazards which do not result in classification
none
6. Synthesis Route
1190307-88-0Total: 13 Synthesis Route
8. Other Information
- 8.0 Mechanism of action and resistance
- Sofosbuvir is a pyrimidine nucleotide analogue (Fig. 1) that inhibits HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication[11, 12], Sofosbuvir is a prodrug that undergoes intracellular metabolism in human hepatocytes to a pharmacologically active uridine triphosphate form (GS-461203)[11-14]. GS-461203 is incorporated into HCV RNA by NS5B polymerase where it acts as a chain terminator[11, 12]. In vitro, the GS-461203 concentration leading to 50 % inhibition of the polymerase activity of recombinant NS5B from HCV genotype 1b, 2a, 3a and 4a ranged from 0.7 to 2.6 micromolar per liter. A rapid rate of viral decline was seen with Sofosbuvir[20]. It was estimated that 99 and 99.9 % of final effectiveness would be reached in a mean 0.8 and 2 days, respectively[20]. HCV RNA levels declined in a biphasic manner[20].
Sofosbuvir has a high genetic barrier to resistance[15]. Studies have found that resistance-associated variants (including the primary sofosbuvir resistance mutation in NS5B, S282T) were not detected in any patient receiving sofosbuvir in combination with ribavirin with or without peginterferon-alpha[15, 16]. However, the S282T resistance mutation was detected in one patient with HCV genotype 2b infection who received sofosbuvir monotherapy. Although L159F and V321A substitutions were detected in some patients with HCV genotype 3a infection who received sofosbuvir-containing regimens in phase III trials, these substitutions were not associated with changes in phenotypic susceptibility of sofosbuvir[12]. In patients with HCV genotype 1a or 2b infection and HCC who received sofosbuvir and ribavirin for up to 48 weeks while awaiting liver transplantation, the L159F substitution emerged in multiple patients who experienced virological failure (breakthrough and relapse)[12]. The presence of L159F and/or C316N substitutions at baseline was also associated with post-transplant virological breakthrough and relapse in multiple patients with HCV genotype 1b infection[12].
HCV replicons expressing the S282T resistance mutation showed low level resistance to sofosbuvir, but retained susceptibility to ribavirin and other classes of direct-acting antivirals, including NS5A inhibitors[17]. Sofosbuvir retained full activity against the nucleoside inhibitor resistance-associated variants L159F and L320F, the ribavirin resistance-associated variants T390I and F415Y, and against clinically relevant protease inhibitor, non-nucleoside inhibitor and NS5A inhibitor resistance-associated variants[18, 19] - View all
- 8.1 Adverse reactions
- Oral sofosbuvir was generally well tolerated in patients with chronic hepatitis C. The most commonly reported adverse events and laboratory abnormalities in patients receiving sofosbuvir plus ribavirin with or without peginterferon-alpha were consistent with those expected in patients receiving treatment with ribavirin and peginterferon-alpha, and co-administering sofosbuvir did not appear to increase the frequency or severity of these adverse events or laboratory abnormalities.
- 8.2 Description
- Sofosbuvir is a drug used for the treatment of hepatitis C. It is recommended to be used in combination with other drugs (such as velpatasvir) for the first-line treatment for HCV genotypes 1, 2, 3, 4, 5, and 6. It takes effect through acting as a nucleotide analog inhibitor, being capable of specially inhibiting the HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase.
- 8.3 Definition
- ChEBI: A nucleotide conjugate that is used in combination with ledipasvir (under the trade name Harvoni) for the treatment of chronic hepatitis C genotype 1 infection.
- 8.4 Uses
- PSI-7977 is a phosphoramidate prodrug of PSI-7851, a nucleoside analog that, when phosphorylated, inhibits the RNA-dependent RNA polymerase of hepatitis C virus (EC50 = 92 nM). PSI-7977 is effective in vitro and in vivo.[Cayman Chemical]
9. Computational chemical data
- Molecular Weight: 529.45300g/mol
- Molecular Formula: C22H29FN3O9P
- Compound Is Canonicalized: True
- XLogP3-AA: 1
- Exact Mass: 529.16254467
- Monoisotopic Mass: 529.16254467
- Complexity: 913
- Rotatable Bond Count: 11
- Hydrogen Bond Donor Count: 3
- Hydrogen Bond Acceptor Count: 11
- Topological Polar Surface Area: 153
- Heavy Atom Count: 36
- Defined Atom Stereocenter Count: 6
- Undefined Atom Stereocenter Count: 0
- Defined Bond Stereocenter Count: 0
- Undefined Bond Stereocenter Count: 0
- Isotope Atom Count: 0
- Covalently-Bonded Unit Count: 1
- CACTVS Substructure Key Fingerprint: AAADceB7PQIAAAAAAAAAAAAAAAAAASAAAAAwQAAAAAAAAAABAAAAHwAQiCAADDzhkAYzDoPABxCIQCHWWICCAAAgIgAIiIGOCMiLNiKAkRKPcAAv1zMLiMewcAIMAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA==
10. Question & Answer
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Are you wondering what Sofosbuvir is and what diseases it can treat? How does it work? Many people find themselves unsure of how to answer these questions. In this article, we will provide you with th..
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There are thousands of types of diseases, and there are also many types of drugs for treating these diseases. It is important to be aware of the differences when using these drugs because some drug na..
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Background Sofosbuvir, a prodrug metabolized to the active antiviral drug 2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-monophosphate, is currently in Phase 3 clinical trials for the treatment of hepati..
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In recent years, with the introduction of more direct-acting antiviral drugs, Sofosbuvir has gradually moved away from the use of interferon and/or ribavirin, which have more side effects. It is now c..
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Sofosbuvir
- Purity:99%Packing: 200kg/bag FOB
- Price: 1 USD/kilogram
- Time: 2023/07/07
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