1172127-80-8Relevant articles and documents
6-(Het)aryl-7-deazapurine ribonucleosides as novel potent cytostatic agents
Nau?, Petr,Pohl, Radek,Votruba, Ivan,D?ubák, Petr,Hajdúch, Marián,Ameral, Ria,Birku?, Gabriel,Wang, Ting,Ray, Adrian S.,Mackman, Richard,Cihlar, Tomas,Hocek, Michal
supporting information; experimental part, p. 460 - 470 (2010/05/02)
A series of novel 7-deazapurine ribonucleosides bearing an alkyl, aryl, or hetaryl group in position 6 and H, F, or Cl atom in position 7 has been prepared either by Pd-catalyzed cross-coupling reactions of the corresponding protected 6-chloro-(7-halogenated-)7-deazapurine ribonucleosides with alkyl- or (het)-arylorganometallics followed by deprotection, or by single-step aqueous phase cross-coupling reactions of unprotected 6-chloro-(7-halogenated-)7- deazapurine ribonucleosides with (het)arylboronic acids. Significant cytostatic effect was detected with a substantial proportion of the prepared compounds. The most potent were 7-H or 7-F derivatives of 6-furyl- or 6-thienyl-7-deazapurines displaying cytostatic activity in multiple cancer cell lines with a geometric mean of 50% growth inhibition concentration ranging from 16 to 96 nM, a potency comparable to or better than that of the nucleoside analogue clofarabine. Intracellular phosphorylation to mono- and triphosphates and the inhibition of total RNA synthesis was demonstrated in preliminary study of metabolism and mechanism of action studies. 2009 American Chemical Society.