5-fluorocytosine flucytosine

Traces (0.1%) of 2-l luoro-/)-alanine were also found in the urine of patients treated with the antifungal agent flucytosine (5-fluorocytosine, 4.239) [156], However, it appears that flucytosine, the amino analogue of 5-fluoro-... 

Flucytosine Flucytosine, 5-fluorocytosine (35.4.4), is synthesized from fluorouracil (30.1.3.3). Fluorouracil is reacted with phosphorous oxychloride in dimethylaniline to make 2,4-dichloro-5-fluoropyrimidine (35.4.2), which is reacted with ammonia to make a product substituted with chlorine at the fourth position of the pyrimidine ring—4-amino-2-chloro-5-fluoropyrimidine (35.4.3). Hydrolysis of the chlorovinyl fragment of this compound in a solution of hydrochloric acid gives the desired flucytosine [52-55]. 

The antifungal flucytosine (5-fluorocytosine) is an inhibitor of the sterol C-14 demethylase. This latter is an enzyme involved in ergosterol biosynthesis, an element of the fungal wall. It is marketed as an antifungal, while the nucleoside derivatives of 5-fluorocytosine emtricitabine, elvucitabin, and FdCyd (287220)) are used for treatment of viral infection and cancer (Figure 8.6). 

Flucytosine (5-fluorocytosine) is also an inhibitor of lanosterol C-14 demethylase (Figure 8.3) with the same indications as fluoroazoles. 

Flucytosine (5-fluorocytosine) is metabolised in the fungal cell to 5-fluorouracil which inhibits nucleic acid synthesis. It is weU absorbed from the gut, penetrates effectively into tissues and almost all is excreted unchanged in the urine (t) 4 h). The dose should be reduced for patients with impaired renal function, and the plasma concentration should be monitored. The drug is well tolerated when renal function is normal. Candida albicans rapidly becomes resistant to flucytosine which ought not to be used alone it may be combined with amphotericin (see Table 14.2) but this increases the risk of adverse effects (leucopenia, thrombocytopenia, enterocolitis) and it is reserved for serious infections where the risk-benefit balance is favourable (e.g. Cryptococcus neoformans meningitis). 

From the interference by flucytosine (5-fluorocytosine) a method of identification was developed for the drug itself. This is calculated from difference between crea-tinineEkiachem creatinineki i j.ff (E167, E302, E443). 

Flucytosine (5-fluorocytosine), 6, is a synthetic nucleoside that is converted intracellularly to 5-fluorouracil which, consequently, interferes with protein synthesis [22]. Although this drug is indicated for disseminated cryptococcosis and disseminated candidiases, flucytosine is rarely used alone due to substantial resistance developed by many opportunistic fungal pathogens. It also has the side effect of suppressing bone marrow production which is particularly problematic in AIDS patients. Flucytosine is sometimes used in combination with amphotericin B to suppress the rapid development of resistance to the flucytosine, but the toxicity appears to increase dramatically in these circumstances [21]. 

Flucytosine(5-fluorocytosine 5-FC 4-amino-5-fluoro-2-pyrimidone) 217 is an antimetabolite type of antifungal drug. It is activated by deamination within the fungal cells to 177. 

Flucytosine. Flucytosine (17) or 5-fluorocytosine (4-amino-5-fluoro-2-pyrimidone, 5-FC), C H FN O, is a pyrimidine derivative, that is efficient against Candida albicans Cryptococcus neoformans and Torulopsis glabrata. 

Flucytosine, USP. 5-Fluonx ytosine. 5-FC. 4-amino-3-lluoro-2( l//)-pyrimidinone. 2-hydroxy-4-amiiio-5-fluoro-pyriiniditie (Ancobon). S-Fluorocytosine is an orally active mlifungal agent with a very narrow spectrum of activity. It is indicated only for the treatment of seriou.s systemic infections caused by susceptible strains of Caiutida and Cryp-Uicomis. spp. 

One other NP-derived molecule that is also in clinical use predominately against yeasts is the modified pyrimidine nucleoside, 5-fluorocytosine (flucytosine) (35, Figure 8), which although made synthetically, can be considered to be derived from a NP. Following transport into Candida or Cryptococcus a cytosine permease,... 

Flucytosine (5 FC, 5-fluorocytosine) is indicated in the treatment of septicemia, endocarditis, and urinary tract infection (Candida), and in meningitis and pulmonary infections (Cryptococcus). Flucytosine, which usually is used in combination with amphotericin B, has activity against Candida and Cryptococcus in both in vivo and in vitro systems. Flucytosine is absorbed well, distributed throughout the body. 

Flucytosine is a fluorinated pyrimidine related to fluorou-racil and floxuridine. It is a 5-fluorocytosine. Flucytosine has clinically useful activity against Cryptococcus neofor-mans, Candida spp., and the agents of chlomoblastomycosis. Within these species, determination of susceptibility in vitro has been extremely dependent on the method employed, and susceptibility testing perfonned on isolates obtained prior to treatment has not correlated with clinical outcome. 

As shown in Scheme 12.54, oxathiolane nucleoside 230, has been prepared by the method of Schinazi and Liotta." Thus, the coupling of sUylated flucytosine 231 preparing from 217 with lactol 232 gave racemic compound, 2-hydroxymethyl-5-(5-fluorocytosin-l-yl)-l,3-oxathiolane [( )-FTC], which afforded the title compound 230 after an enantioseiective enzymic resolution and hydrolysis. 

Flucytosine 4.23) (5-fluorocytosine, Ancobon ) has proved clinically successful as an orally active fungicide for treating such systemic diseases as candidosis and cryptococcal meningitis (Bennett, 1977). Its selectivity depends on the fact that mammals secrete it unchanged (just as they do cytosine), whereas fungi convert it to 5-fluorouracil and then elaborate this to its cytostatic nucleotide. 

Flucytosine, or 5-fluorocytosine, is a synthetic antimycotic drug discovered in 1957. 

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