Flucytosine

Base Information

• Chemical Name: Flucytosine
• CAS No.: 2022-85-7
• Molecular Formula: C4H4FN3O
• Molecular Weight: 129.094
• Hs Code.: 29335990
• European Community (EC) Number: 217-968-7
• NSC Number: 759130,103805
• UNII: D83282DT06
• DSSTox Substance ID: DTXSID3023059
• Nikkaji Number: J3.695A
• Wikipedia: Flucytosine
• Wikidata: Q238490
• NCI Thesaurus Code: C501
• RXCUI: 4451
• Metabolomics Workbench ID: 43329
• ChEMBL ID: CHEMBL1463
• Mol file: 2022-85-7.mol

Synonyms:5-Fluorocytosine;Alcobon;Ancobon;Ancotil;Flucytosine

Chemical Property of Flucytosine

Chemical Property:

• Appearance/Colour: white crystalline solid
• Vapor Pressure: 0.0492mmHg at 25°C
• Melting Point: 298-300 °C (dec.)(lit.)
• Refractive Index: 1.613
• Boiling Point: 298oC
• PKA: 3.26(at 25℃)
• Flash Point: 96.4°C
• PSA: 71.77000
• Density: 1.73 g/cm³
• LogP: 0.07240
• Storage Temp.: 2-8°C
• Sensitive.: Light Sensitive
• Solubility.: Sparingly soluble in water, slightly soluble in ethanol (96 per cent)
• Water Solubility.: 1.5g/100mL (25 ºC)
• XLogP3: -0.9
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 0
• Exact Mass: 129.03383992
• Heavy Atom Count: 9
• Complexity: 208

Purity/Quality:

99.0%min ^*data from raw suppliers

5-Fluorocytosine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn, T, Xi
• Hazard Codes: Xn,T,Xi
• Statements: 40-36/37/38-63
• Safety Statements: 22-24/25-45-36/37-36/37/39-27-26

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antifungal Agents
• Canonical SMILES: C1=NC(=O)NC(=C1F)N
• Recent ClinicalTrials: Clinical Study of ABCD in the Treatment of Cryptococcal Meningitis
• Recent EU Clinical Trials: A dose escalation and phase IIa study of TG6002 plus flucytosine in patients with unresectable colorectal cancer with liver metastases
• Description: 5-Fluorocytosine (5-FC), a fluorinated pyrimidine analog, is a synthetic antimycotic prodrug that is converted by cytosine deaminase to 5-fluorouracil. 5-Fluorouracil, a widely used cytotoxic drug, is further metabolized to fluorinated ribo- and deoxyribonucleotides, resulting in the inhibition of DNA and protein synthesis, which has multiple effects including inhibition of Candida species and C. neoformans infections and cytotoxicity towards cancer cells. In combination with a retroviral replicating vector carrying a cytosine deaminase prodrug-activating gene, 5-FC has been shown to selectively eliminate CT26 and Tu-2449 tumor cells in vitro (IC50s = 4.2 and 1.5 μM, respectively) and to significantly improve survival and reduce tumor size (at a dose of 500 mg/kg) in two different syngeneic mouse glioma models.
• Uses: 5-Fluorocytosine acts as an antidiabetic, antifungal and antimicrobial agent. It is useful for the treatment of serious infections arises due to susceptible strains of Candida or Cryptococcus neoformans and chromomycosis. Further, it is employed in studies on TMP biosynthesis. antidiabetic antifungal and antimicrobial agent 5-FC is a toxic antifungal/antimicrobial agent
• Indications: Flucytosine (Ancobon) is a synthetic, fluorinated pyrimidine that is structurally related to fluorouracil (FU) and floxuridine. It can be fungistatic and fungicidal. Although it is used more frequently in the treatment of systemic infections caused by Candida and Cryptococcus, dermatologic indications may include infections due to chromomycosis, sporotrichosis, Cladosporium, and Sporothrix species. It is generally ineffective against Aspergillus species.
• Therapeutic Function: Antifungal
• Clinical Use: 5-Fluorocytosine, 5-FC, 4-amino-5-fluoro-2(1H)-pyrimidinone, 2-hydroxy-4-amino-5-fluoropyrimidine (Ancobon). 5-Fluorocytosine is an orally active antifungal agent with a very narrow spectrum of activity. It is indicated only for the treatment of serious systemic infections caused by susceptible strains of Candida and Cryptococcus spp.The mechanism of action of 5-fluorocytosine (5-FC)has been studied in detail.The drug enters the fungal cell by active transport onATPases that normally transport pyrimidines. Once insidethe cell, 5-fluorocytosine is deaminated in a reaction catalyzedby cytosine deaminase to yield 5-fluorouracil(5-FU). 5-Fluorouracil is the active metabolite of the drug.5-Fluorouracil enters into pathways of both ribonucleotideand deoxyribonucleotide synthesis. The fluororibonucleotidetriphosphates are incorporated into RNA, causingfaulty RNA synthesis. This pathway causes cell death. Inthe deoxyribonucleotide series, 5-fluorodeoxyuridinemonophosphate (F-dUMP) binds to 5,10-methylenetetrahydrofolicacid, interrupting the one-carbon pool substratethat feeds thymidylate synthesis. Hence, DNA synthesisis blocked. Flucytosine has significant antifungal activity against C. albicans, other Candida spp., C. neoformans, and the fungal organisms responsible for chromomycosis. Not considered the drug of choice for these fungal infections, 5-FC does remain useful as part of combination therapy for systemic candidiasis and cryptococcal meningitis and as an alternative drug for chromomycosis. When it is used as monotherapy, resistance and clinical failure are common. Potential mechanisms for drug resistance include decreased fungal cell membrane permeability and reduced levels of fungal cytosine deaminase. Combination therapy with amphotericin B and flucytosine in the treatment of cryptococcal meningitis and deep-seated Candida infections, such as septic arthritis and meningitis, permits reduced dosing of amphotericin B and prevents the emergence of 5-FC resistance. When higher doses of amphotericin B are used, combination therapy with 5-FC confers no additional clinical benefit except in the treatment of Candida endophthalmitis, where tissue penetration remains problematic. Candidosis (in combination with amphotericin B or fluconazole) Cryptococcosis (in combination with amphotericin B or fluconazole) Monitoring of flucytosine concentrations is desirable in all patients, and mandatory in those with renal impairment.
• Drug interactions: Potentially hazardous interactions with other drugs Cytarabine: concentration of flucytosine possibly reduced.

Technology Process of Flucytosine

There total 21 articles about Flucytosine 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: 98.1%

2,5-difluoro-4-chloro-pyrimidine (99429-06-8) → Flucytosine (2022-85-7)

Guidance literature:

With ammonia; In hydrogenchloride; ethanol; water;

Reference yield: 98.0%

→ Flucytosine (2022-85-7)

Guidance literature:

Reference yield: 95.7%

Cytosine (71-30-7) → Flucytosine (2022-85-7)

Guidance literature:

Cytosine; With hydrogen fluoride; at -15 - 0 ℃; Inert atmosphere;

at -20 ℃; for 4h; Further stages; Inert atmosphere;

upstream raw materials:

2-ethylsulfanyl-5-fluoro-pyrimidin-4-ylamine

Cytosine

β-D-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine

2,5-difluoro-4-chloro-pyrimidine

Downstream raw materials:

N¹-(4-benzoyl-2-butyn-1-yl)-5-fluorocytosine

1-(3,5-O-dibenzoyl-2-fluoro-β-D-arabinofuranosyl)-5-fluorocytosine

4-amino-5-fluoro-1-<<2-(benzoyloxy)-1-<(benzoyloxy)methyl>ethoxy>methyl>cytosine

5-fluorouracil

Refernces

• 1、 Shi, Junxing,Ray, Adrian S.,Mathew, Judy S.,Anderson, Karen S.,Chu, Chung K.,Schinazi, Raymond F.. "2′,3′-didehydro-2′,3′-dideoxynucleosides are degraded to furfuryl alcohol under acidic conditions". . p. 2159 - 2162. Retrieved 2004.
• 2、 Dietz, Jule-Philipp,Derstine, Brenden P.,Ferenc, Dorota,Crawford, Evan T.,Arduengo, Anthony J.,Gupton, B. Frank,McQuade, D. Tyler,Opatz, Till. "Synthesis of 5-Fluorocytosine Using 2-Cyano-2-fluoroethenolate as a Key Intermediate". . p. 5519 - 5526. Retrieved 2019/07/17.
• 3、 -. "Method for synthesizing 5-fluorocytosine". Paragraph 0028-0029; 0031. . Retrieved 2020/01/08.