Emtricitabine

Base Information

• Chemical Name: Emtricitabine
• CAS No.: 143491-57-0
• Deprecated CAS: 145213-48-5
• Molecular Formula: C8H10FN3O3S
• Molecular Weight: 247.25
• Hs Code.: 2934990002
• European Community (EC) Number: 604-363-1
• UNII: G70B4ETF4S,ULS8902U4O
• DSSTox Substance ID: DTXSID0040129
• Nikkaji Number: J523.685A
• Wikipedia: Emtricitabine,Racivir
• Wikidata: Q422604
• NCI Thesaurus Code: C47509
• RXCUI: 276237
• Metabolomics Workbench ID: 43154
• ChEMBL ID: CHEMBL885
• Mol file: 143491-57-0.mol

Synonyms:2(1H)-Pyrimidinone,4-amino-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-, (2R-cis)-;(-)-2',3'-Dideoxy-5-fluoro-3'-thiacytidine;(-)-2'-Deoxy-5-fluoro-3'-thiacytidine;(-)-FTC;524W91;BW 1592;BW 524W91;Coviracil;Emtriva;FTC, (-)-;

Chemical Property of Emtricitabine

Chemical Property:

• Appearance/Colour: white to off-white crystalline solid
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 136-140 °C
• Refractive Index: 1.731
• Boiling Point: 443.3 °C at 760 mmHg
• PKA: 13.83±0.10(Predicted)
• Flash Point: 221.9 °C
• PSA: 115.67000
• Density: 1.82 g/cm³
• LogP: 0.12620
• Storage Temp.: -20°C Freezer
• Solubility.: Chloroform (Slightly)
• XLogP3: -0.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 2
• Exact Mass: 247.04269053
• Heavy Atom Count: 16
• Complexity: 374

Purity/Quality:

99%, ^*data from raw suppliers

Fumitremorgin C ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiviral Agents
• Canonical SMILES: C1C(OC(S1)CO)N2C=C(C(=NC2=O)N)F
• Isomeric SMILES: C1[C@H](O[C@H](S1)CO)N2C=C(C(=NC2=O)N)F
• Recent ClinicalTrials: Empiric Treatment for Acute HIV in the ED
• Recent EU Clinical Trials: A randomised non-inferiority trial with nested PK to assess DTG/3TC fixed dose formulations for the maintenance of virological suppression in children
• Description: Emtricitabine is a nucleoside reverse transcriptaseinhibitor (NRTI) which has been marketed for the prevention and treatment of HIV infection. It also exhibits clinical activity against the hepatitis B virus (HBV) (not yet approved by FDA).Emtricitabine is a synthetic nucleoside analogue of cytidine. It can be phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate, which competes with the natural substrate deoxycytidine 5'-triphosphate and incorporates into nascent viral DNA, causing early chain termination. Through doing this, it not only lowers the amount of HIV, but also indirectly increases the number of immune system cells (called T cells or CD4+ T-cells). Emtricitabine is a synthetic nucleoside inhibitor of HIV-1 reverse transcriptase. Its mechanism of action entails the phosphorylation of the oxathiolane carbinol function by cellular enzymes to form the corresponding 5′-triphosphate, which competes with the endogenous 2′-deoxycytidine 5′-triphosphate substrate. The in vitro activity of emtricitabine ranges from IC50 of 0.00013 to 0.64 mM against lymphoblastoid cell lines, MAGI-CCR5 cell lines, and peripheral blood mononuclear cells. Emtricitabine is prepared in about 16 steps from L-gulose, from which the O–C–S carbon stereochemistry is derived in the formation of substituted key 4-O-Acetyl-1,3- oxathiolane intermediate. This intermediate is coupled with N-benzoyl-O-trimethylsilyl- 5-fluoro-cytosine in the presence of trimethylsilyl triflate. The resulting anomeric mixture is separated by silica chromatography and subjected to two deprotection steps. Emtricitabine resistant isolates (M184V/I) were cross-resistant to lamivudine (desfluoro version of emtricitabine) and zalcitabine but remained sensitive to abacavir, didanosine, stavudine, tenofovir, zidovudine, and non-nucleoside reverse transcriptase inhibitors (delavirdine, efavirenz, and nevirapine). In a 48-week clinical trial using emtricitabine with didanosine and efavirin versus stavudine, didanosine and efavirenz produced 81 versus 68% responder rate respectively. In one study, 37.5% of treatment na?¨ve patients that were not achieving successful viral levels were found to exhibit a reduced potency toward emtricitabine. This resistance was due to M184V/I mutation in the HIV reverse transcriptase gene. Recommended dosing of emtricitabine is 200 mg (capsule) once per day. It is 93% bio-available and has a plasma half-life about 10 h, with 86% renal clearance. Side effects associated with emtricitabine treatment were generally mild to moderate and included headache, diarrhea, nausea, and rash. A generally mild and asymptomatic hyperpigmentation of the palms and/or soles was also observed.
• Indications: 1. Emtricitabine is combined with other antiviral drugs for treating adult HIV-1 infection. Patients should be those who haven’t been subject to treatment by reverse transcriptase inhibitors or those who have received reverse transcriptase inhibitors with virus having been suppressed. 2. It can be used for the treatment of chronic hepatitis B.
• Uses: It is white, white-like powder or crystalline powder Application: treatment of chronic hepatitis B; It has a strong antiviral activity with the safety and tolerance being good. A reverse transcriptase inhibitor. A nucleoside analog structurally related too lamivudine.It is an effective antiviral agent against HIV, HBV, and other viruses replicating in a similar manner. A nucleoside analog structurally related to Lamivudine (L172500). anti-Alzheimer’s treatment Labeled Emtricitabine, intended for use as an internal standard for the quantification of Emtricitabine by GC- or LC-mass spectrometry.
• Clinical Use: Treatment of HIV infection (in combination with other antiretroviral drugs)
• Drug interactions: Potentially hazardous interactions with other drugs Antivirals: avoid concomitant use with lamivudine. Orlistat: absorption of emtricitabine possibly reduced.

Technology Process of Emtricitabine

There total 16 articles about Emtricitabine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 93.2%

2',3'-dideoxy-5-fluoro-3'-thiacytidine hydrochloride (258832-61-0) → emtricitabine (143491-57-0,144371-00-6,145213-48-5,145986-26-1)

Guidance literature:

With triethylamine; In methanol; at 15 - 60 ℃;

Reference yield: 91.88%

(2R,5S)-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine salicylate → emtricitabine (143491-57-0,144371-00-6,145213-48-5,145986-26-1)

Guidance literature:

With triethylamine; In ethanol; at 50 ℃; for 1h;

Reference yield: 90.0%

4-amino-5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one; benzoic acid → emtricitabine (143491-57-0,144371-00-6,145213-48-5,145986-26-1)

Guidance literature:

With Isopropyl acetate; triethylamine; at 15 - 30 ℃; for 4h; Reagent/catalyst;

upstream raw materials:

(-)-(2R,5S)-5-fluoro-1-<2-<<(tert-butyldiphenylsilyl)oxy>methyl>-1,3-oxathiolan-5-yl>-N⁴-benzoylcytosine

(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathiolane-2-carboxylate

2',3'-dideoxy-5-fluoro-3'-thiacytidine hydrochloride

4-amino-5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-[1,3]-oxathiolan-5-yl]-(1H)-pyrimidin-2-one monosuccinate

Downstream raw materials:

C₅₈H₇₂F₂N₆O₁₂S

(-)-N₄-(4,4'-dimethoxytrityl)-5-fluoro-2',3'-dideoxy-3'-thiacytidine

Refernces

• 1、 -. "Emtricitabine synthesis method". Paragraph 0028; 0035; 0036; 0038. . Retrieved 2019/11/29.
• 2、 -. "A Suitqable to preparation method". Paragraph 0042; 0064-0066. . Retrieved 2019/04/02.