- Rapid continuous synthesis of 5′-deoxyribonucleosides in flow via Br?nsted acid catalyzed glycosylation
-
A general, green, and efficient Br?nsted acid-catalyzed glycosylation serves as a key step in the one-flow, multistep syntheses of several important 5′-deoxyribonucleoside pharmaceuticals.
- Shen, Bo,Jamison, Timothy F.
-
p. 3348 - 3351
(2012/08/08)
-
- The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, Capecitabine
-
To identify an orally available fluoropyrimidine having efficacy and safety profiles greatly improved over those of parenteral 5-fluorouracil (5-FU: 1), we designed a 5-FU prodrug that would pass intact through the intestinal mucisa and be sequentially converted to 5-FU by enzymes that are highly expressed in the human liver and then in tumors. Among various N4-substituted 5'-deoxy-5-fluorocytidine derivatives, a series of N4-alkoxycarbonyl derivatives were hydrolyzed to 5'-deoxy-5-fluorocytidine (5'-DFCR: 8) specifically by carboxylesterase, which exists preferentially in the liver in humans and monkeys. Particularly, derivatives having an N4-alkoxylcarbonyl moiety with a C4-C6 alkyl chain were the most susceptible to the human carboxylesterase. Those were then converted to 5'-deoxy-5-fluorouridine (5'-DFUR: 4) by cytidine deaminase highly expressed in the liver and solid tumors and finally to 5-FU by thymidine phosphorylase (dThdPase) preferentially located in tumors. When administered orally to monkeys, a derivative having the N4-alkoxylcarbonyl moiety with a C5 alkyl chain (capecitabine: 6) The highest AUC and Cmax for plasma 5'-DFUR. In tests with various human cancer xenograft models, capecitabine was more efficacious at wider dose ranges than either 5-FU or 5'-DFUR and was significantly less toxic to the intestinal tract than the others in monkeys. Copyright (C) 2000 Elsevier Science Ltd.
- Shimma, Nobuo,Umeda, Isao,Arasaki, Motohiro,Murasaki, Chikako,Masubuchi, Kazunao,Kohchi, Yasunori,Miwa, Masanori,Ura, Masako,Sawada, Noriaki,Tahara, Hitoshi,Kuruma, Isamu,Horii, Ikuo,Ishitsuka, Hideo
-
p. 1697 - 1706
(2007/10/03)
-
- Process for producing N4 -acyl-5'-deoxy-5-fluorocytidine compounds
-
A novel process for producing derivatives of the anti-tumor agent N4 -acyl-5'-deoxy-5-fluorocytidine using the novel 5'-deoxy-5-fluoro-N4, 2'-0,3'-0-triacylcytidine derivatives as intermediates is provided. 5-Deoxy-1,2,3-tri-0-acyl-β-D-ribofuranoside is reacted with 5-fluorocytosine to produce 5'-deoxy-2',3'-di-0-acyl-5-fluorocytidine, followed by acylation, to produce the novel intermediate 5'-deoxy-5-flouro-N4,2'-0,3'-0-triacylcytidine. The acyl radicals of this intermediate are selectively de-0-acylated to obtain N4 -acyl-5'-deoxy-5-fluorocytidine derivatives. From fluorocytosine, N4 -acyl-5'-deoxy-5-fluorocytidine derivatives can be obtained through few steps in high yield, an in satisfactory purity.
- -
-
-
- Fluorocytidine derivatives
-
The novel 5'-deoxy-5-fluorocytidine derivatives of formula STR1 wherein R1, R2 and R3 are hydrogen or an easily hydrolyzable radical under physiological conditions, with the proviso that, at least one or R1, Rs
- -
-
-