6-(Het)aryl-7-Deazapurine Ribonucleosides as Novel Potent Cytostatic Agents
6-(Het)aryl-7-Deazapurine Ribonucleosides as Novel Potent Cytostatic Agents
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DOI：
10.1021/jm901428k
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发表时间：
2010-01-14
影响因子：
7.3
通讯作者：
Hocek, Michal
中科院分区：
文献类型：
--
作者：
Naus, Petr;Pohl, Radek;Hocek, Michal
A series of novel 7-deazapurine ribonucleosides bearing an alkyl, aryl, or lietaryl 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-clilot-o-(7-h ilogeiiztted-)7-deiz ipurine ribonucleosides with alkyl- or (het)arylorganometallics followed by deprotection, or by single-step aqueous phase cross-coupling reactions of unprotected 6-chloro-(7-lialogen tted-)7-de iz tl)tii-iiie ri bon ucleos ides with (het)arylboronic acids. Significant cytostatic effect was detected With a Substantial proportion ofthe prepared compounds. The most potent were 7-H or 7-17 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 clofarabinc. lntr icel]Lll ll'pliosphoi-yl itioil to niono- and triphosphates and the inhibition of total RNA synthesis was denionstrated in preliminary study of metabolism and tinechanistin of action Studies.
