176685-71-5Relevant academic research and scientific papers
Nucleosides and nucleotides. 176. 2'-Deoxy-2'-hydroxylaminocytidine: A new antitumor nucleoside that inhibits DNA synthesis although it has a ribonucleoside structure
Ogawa, Akira,Shuto, Satoshi,Inanami, Osamu,Kuwabara, Mikinori,Tanaka, Motohiro,Sasaki, Takuma,Matsuda, Akira
, p. 1913 - 1918 (2007/10/03)
The design and synthesis of potential antitumor antimetabolites 2'- deoxy-2'-hydroxylaminouridine (2'-DHAU) and -cytidine (2'-DHAC) are described. We found that 2'-DHAC in neutral solution generated 2'-aminoxy radicals at room temperature. 2'-DHAC inhibited the growth of L1210 and KB cells, with IC50 values of 1.58 and 1.99 μM, respectively, more potently than 2'-DHAU, with IC50 values of 34.5 and 27.3 μM, respectively. 2'-DHAC was effective against 9 human cell lines, with IC50 values in the micromolar range. The in vivo antitumor activity of 2'-DHAC was also examined using the mouse leukemia P388 model, which gave a T/C value of 167%. Phosphorylation of 2' -DHAC by uridine/cytidine kinase was essential for its cytotoxicity, as suggested by a competition experiment using several common nucleosides. Inhibition of DNA synthesis was the predominant mechanism of action of 2'-DHAC, although it has a ribo-configuration.
Novel nucleosides via intramolecular functionalization of 2,2'-anhydrouridine derivatives
McGee,Sebesta,O'Rourke,Martinez,Jung,Pieken
, p. 1995 - 1998 (2007/10/03)
The generation of novel ribonucleoside analogues derived from 2,2'-anhydrouridines by a 3'-hydroxyl directed intramolecular nucleophilic substitution of the 2'-position is described. The methodology allows for the efficient, regio- and stereoselective elaboration of the 2'-position, often under exceptionally mild reaction conditions.
2'-Deoxy-2'-alkoxyaminouridines: Novel 2'-substituted uridines prepared by intramolecular nucleophilic ring opening of 2,2'-O-anhydrouridines
Sebesta, David P.,O'Rourke, Sarah S.,Martinez, Rogelio L.,Pieken, Wolfgang A.,McGee, Danny P. C.
, p. 14385 - 14402 (2007/10/03)
Natural and unnatural modified nucleosides and nucleotides play important roles in biology, medicine, and as biomedical research tools. Reported herein is an application of synthetic methodology developed for the stereo- and regiospecific introduction of structural modifications at the 2'-position of uridine nucleosides. A novel class of modified nucleosides, 2'-alkoxylamino-2'-deoxy uridines, are prepared by intramolecular nucleophilic addition of a 3'-tethered alkoxycarbamate nucleophile to the 2'-position with concomitant opening of a 2,2'-anhydrouridine.
