5-Fluorouracil derivatives. XII. Synthesis and antitumor activity of .ALPHA.-alkylthiomethyl-, .ALPHA.-alkylsulfinylmethyl-, .ALPHA.-alkylsulfonylmethyl-, and .ALPHA.-acylthiomethyl-5-fluorouracils.

Ozaki, Shoichiro; Nagase, Tsuyoshi; Tamai, Hiromichi; Mori, Haruki; Hoshi, Akio; Iigo, Masaaki

doi:10.1248/cpb.35.3894

Cited by 9 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…12,17,18 However, the base-catalyzed alkylation of 5-FU by ACOM chlorides has probably been used most frequently. 12,17,18 However, the base-catalyzed alkylation of 5-FU by ACOM chlorides has probably been used most frequently.…”

Section: Resultsmentioning

confidence: 99%

1-Alkylcarbonyloxymethyl Prodrugs of 5-Fluorouracil (5-FU): Synthesis, Physicochemical Properties, and Topical Delivery of 5-FU

Taylor

Sloan

1998

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

1-Alkylcarbonyloxymethyl (1-ACOM) prodrugs of 5-fluorouracil (5-FU) have been synthesized and characterized by their solubilities in isopropyl myristate (SIPM) and pH 4.0 buffer (SH2O), by their partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K) and by their abilities to deliver total 5-FU species into (Cs) and through (Ji) hairless mouse skin from an IPM vehicle. All of the prodrugs were much more lipophilic (SIPM) than 5-FU (> 60 times), and two members of the series (alkyl = C1 and C2, acetyl- and propionyloxymethyl) were also more soluble in water than 5-FU. The two more water-soluble members gave larger Ji values than the other members of the series, with C2 exhibiting the best biphasic solubility and the largest Ji value (16 times that of 5-FU). The ability of the 1-ACOM-5-FU prodrugs to deliver total 5-FU species into skin (Cs) was greater than the delivery of 5-FU by 5-FU, except for the last two members of series (alkyl = C7 and C9, octanoyl- and decanoyl-oxymethyl). However, the ratios of normalized Cs to Ji for the series was less than that exhibited by 5-FU, except for C7 and C9. Also, except for C9, significant amounts of intact prodrug as percentages of total 5-FU species were found in the receptor phases during the course of the diffusion cell experiments, ranging from 55% for C1 to 12% for C7.

show abstract

Section: Resultsmentioning

confidence: 99%

1-Alkylcarbonyloxymethyl Prodrugs of 5-Fluorouracil (5-FU): Synthesis, Physicochemical Properties, and Topical Delivery of 5-FU

Taylor

Sloan

1998

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

Synthesis and Characterization of New Liver Targeting 5‐Fluorouracil‐Cholic Acid Conjugates

Qian

et al. 2009

Archiv der Pharmazie

View full text Add to dashboard Cite

The objective of this work was to develop a liver-specific antihepato carcinoma agent. A series of 5-fluorouracil / cholic acid conjugates (5-FU-cholic acid conjugates) were prepared and tested for their chemical characteristics and bio-distribution properties. The in-vitro stability trial showed 5-FU-cholic acid conjugates could be completely hydrolyzed by heating at 70 degrees C in an acidic solution, pH = 1, for 5 min. The fast and complete hydrolysis of these compounds could be compatible with a fast separation and analysis method to shorten the analysis time. The decomposition speeds of the 5-FU-cholic acid conjugates in different organs of mice at several time points after oral administration were evaluated by measuring the concentrations of regenerated 5-FU in organ tissue. The results were compared with those of the controls, which was a group of mice orally taking 5-FU. The concentrations of 5-FU in mice liver tissue were remarkably increased after oral administration of the prodrugs, and were much larger than if only orally administered 5-FU. The results suggested the feasibility to improve therapeutic efficiency of liver targeting treatments by using cholic acid as the vector of drugs.

show abstract

ChemInform Abstract: 5‐Fluorouracil Derivatives. Part 12. Synthesis and Antitumor Activity of α‐Alkylthiomethyl‐, α‐Alkylsulfinylmethyl‐, α‐Alkylsulfonylmethyl‐, and α‐Acylthiomethyl‐5‐fluorouracils.

et al. 1988

View full text Add to dashboard Cite

show abstract

5-Fluorouracil derivatives. XII. Synthesis and antitumor activity of .ALPHA.-alkylthiomethyl-, .ALPHA.-alkylsulfinylmethyl-, .ALPHA.-alkylsulfonylmethyl-, and .ALPHA.-acylthiomethyl-5-fluorouracils.

Cited by 9 publications

References 0 publications

1-Alkylcarbonyloxymethyl Prodrugs of 5-Fluorouracil (5-FU): Synthesis, Physicochemical Properties, and Topical Delivery of 5-FU

1-Alkylcarbonyloxymethyl Prodrugs of 5-Fluorouracil (5-FU): Synthesis, Physicochemical Properties, and Topical Delivery of 5-FU

Synthesis and Characterization of New Liver Targeting 5‐Fluorouracil‐Cholic Acid Conjugates

ChemInform Abstract: 5‐Fluorouracil Derivatives. Part 12. Synthesis and Antitumor Activity of α‐Alkylthiomethyl‐, α‐Alkylsulfinylmethyl‐, α‐Alkylsulfonylmethyl‐, and α‐Acylthiomethyl‐5‐fluorouracils.

Contact Info

Product

Resources

About