Comparative studies on the antitumor and immunosuppressive effects of the new fluorouracil derivative N4-trimethoxybenzoyl-5'-deoxy-5-fluorocytidine and its parent drug 5'-deoxy-5-fluorouridine.

Miwa, Masanori; Ishikawa, Tohru; Eda, Hiroyuki; Ryu, Mayumi; Fujimoto, Kazuya; Ninomiya, Yasuyuki; Umeda, Isao; Yokose, Kazuteru; Ishitsuka, Hideo

doi:10.1248/cpb.38.998

Cited by 11 publications

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“…Other recently developed nucleoside analogues include the 5-FU prodrug capecitabine (Figure 3) (Miwa et al, 1990). This cytidine analogue is administered as an oral formulation and passes unchanged through the intestinal mucosa.…”

Section: Nucleoside Analoguesmentioning

confidence: 99%

New antimetabolites in cancer chemotherapy and their clinical impact

1998

Br J Cancer

126

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Summary It is almost 50 years since antimetabolites were first found to have clinical antitumour activity, with Farber's discovery that aminopterin could cause remission in acute leukaemia. In the following 10 years, methotrexate, 6-mercaptopurine and 5-fluorouracil (5-FU) found their way into clinical practice. Subsequently, cytosine arabinoside was found to have activity in acute leukaemia, but, until recently, other significant developments have involved optimizing the efficacy of existing antimetabolites, including the use of leucovorin with methotrexate or 5-FU. Recently, new antimetabolites have become a fertile area for anti-cancer drug research. Gemcitabine (GEMZAR®) has emerged as an important new agent in several tumour types, including pancreatic, non-small-cell lung, bladder, breast and ovarian cancers. Capecitabine is an intriguing new prodrug, offering tumour selectivity and prolonged tumour exposure to 5-FU. More potent thymidylate synthase inhibitors have also emerged; raltitrexed is now commercially available for the treatment of colorectal cancer. Others under development include LY231514, which has other sites of action, hence the acronym MTA (multi-targeted antifolate). A novel target is glycinamide ribonucleotide formyltransferase (GARFT) and LY309887 and AG2034 are undergoing clinical investigation as GARFT inhibitors. A critical element with LY309887 appears to be co-administration of folate. It seems entirely possible that several novel antimetabolites will establish themselves in clinical practice in future for the treatment of solid tumours.

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Section: Nucleoside Analoguesmentioning

confidence: 99%

New antimetabolites in cancer chemotherapy and their clinical impact

1998

Br J Cancer

126

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“…In light of the fact that pathogenic bacteria may develop resistance towards conventional antibiotics (Perri et al, 2003), nucleobase containing compounds such as cytosine nucleosides (Isono, 1991) and peptide nucleic acids (Good and Nielsen, 1998) might constitute a potential therapeutic alternative. Various derivatives of the exocyclic amino group (N 4 ) in cytosine containing compounds have been prepared and evaluated as prodrugs: (i) N-mannich bases (Koch and Sloan, 1987); (ii) amides (Miwa et al, 1990;Choe et al, 2002); (iii) alkyloxycarbonyl derivatives (Choe et al, 2002) and 0928-0987/$ -see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.ejps.2004.08.007 (iv) dialkylamino-methylene derivatives (Kerr and Kalman, 1994).…”

Section: Introductionmentioning

confidence: 99%

N4-alkyloxycarbonyl derivatives of cytosine: physicochemical characterisation, and cytosine regeneration rates and release from alginic acid gels

Petersson

Pedersen

Krogfelt

et al. 2004

European Journal of Pharmaceutical Sciences

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Nucleobase containing compounds might constitute a potential alternative to conventional antibiotics in the treatment of Helicobacter pylori infections. N4-alkyloxycarbonyl-cytosine derivatives were synthesized and subjected to basic physicochemical characterisation including assessment of hydrolytic stability in various matrices. pH-rate profiles of selected compounds (range 0-12) were constructed. Hydrolysis of the derivatives in slightly alkaline solution (60 degrees C) resulted in quantitative conversion to parent cytosine whereas at acidic pH (60 degrees C) liberation of cytosine was in most cases accompanied by the parallel formation of uracil. Interestingly the lipophilic N4-adamantyloxycarbonyl-cytosine prodrug exhibited a half-life of 41 min (pH 1.1 at 37 degrees C) with quantitative conversion to parent cytosine, the degradation rate being approximately 200 times faster than that of the non-cyclic aliphatic derivatives investigated. The presence of pig stomach homogenates, pepsin A and H. pylori did not have a noteworthy catalytic effect on the hydrolysis of the derivatives. The release of parent cytosine was markedly delayed from alginic acid gels loaded with the acid-labile and poorly soluble ADC prodrug as compared to gels loaded with parent cytosine.

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G

Collins¹

1998

Dictionary of Carbohydrates

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Comparative studies on the antitumor and immunosuppressive effects of the new fluorouracil derivative N4-trimethoxybenzoyl-5'-deoxy-5-fluorocytidine and its parent drug 5'-deoxy-5-fluorouridine.

Cited by 11 publications

References 0 publications

New antimetabolites in cancer chemotherapy and their clinical impact

New antimetabolites in cancer chemotherapy and their clinical impact

N4-alkyloxycarbonyl derivatives of cytosine: physicochemical characterisation, and cytosine regeneration rates and release from alginic acid gels

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