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| Synthesis and Antitumor Activities of Novel N6-Piperazine Substituted Adenosine Analogues |
| ZHOU Gao-hui, LUO Ming-ming, ZHANG Yang,YU Xiao-qin, TAO Li-ming, XU Wen-ping |
| School of Pharmacy, East China University of Science & Technology, Shanghai 200237, China |
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Abstract The intermediate, {(3R,4R,6R,6R)-2,2-dimethyl-6-［6-(piperazin-1-yl)-9H-purin-9-yl］ tetrahydrofuro［3,4-d］［1,3］dioxol-4-yl}methanol(4), was synthesized by three steps including adjacent hydroxyl protection, chlorination and introduction of piperazine at N6- position, using adenosine as starting material. Eight novel N6-piperazine substituted adenosine analogues(8a~8h) were synthesized by coupling reaction of 4 with 6a~6h, then deprotection of hydroxyl. The structures were characterized by 1H NMR， 13C NMR and HR-ESI-MS. Biological evaluation showed that 8a~8h exhibited antitumor activities on Hela cells, especially, 2-｛4-［9-(3,4-dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-9H-purin-6-yl］-piperazin-1-yl｝-N-(3-fluoro-phenyl)-acetamide(8e) exhibited the strongest inhibitory activity with IC50 of 21.74 μmol·L-1.
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Received: 14 April 2015
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2016, Vol. 24 
