Sugar-modified derivatives of cytostatic 7-(het)aryl-7-deazaadenosines: 2¡ä-C-methylribonucleosides, 2¡ä-deoxy-2¡ä-fluoroarabinonucleosides, arabinonucleosides and 2¡ä-deoxyribonucleosides

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• 作者：Petr Nau? ; Pavla Perl¨ªkov¨¢ ; Aurelie Bourderioux ; Radek Pohl ; Lenka Slav¨§t¨ªnsk¨¢ ; Ivan Votruba ; Gina Bahador ; Gabriel Birku? ; Tom¨¢? Cihl¨¢? ; Michal Hocek
• 关键词：Nucleosides ; Fluorine ; Deazapurines ; Pyrrolo[2 ; 3-d]pyrimidine ; Cytostatics
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 出版时间：1 September, 2012
• 年：2012
• 卷：20
• 期：17
• 页码：5202-5214
• 全文大小：919 K

文摘

A series of novel sugar-modified derivatives of cytostatic 7-hetaryl-7-deazaadenosines (2¡ä-C-methylribonucleosides, 2¡ä-deoxy-2¡ä-fluoroarabinonucleosides, arabinonucleosides and 2¡ä-deoxyribonucleosides) was prepared and screened for biological activity. The synthesis consisted of preparation of the corresponding sugar-modified 7-iodo-7-deazaadenine nucleosides and their aqueous-phase Suzuki-Miyaura cross-coupling reactions with (het)arylboronic acids or Stille couplings with hetarylstannanes in DMF. The synthesis of 7-iodo-7-deazaadenine nucleosides was based on a glycosidation of 6-chloro-7-iodo-7-deazapurine with a suitable sugar synthon or on an interconversion of 2¡ä-OH stereocenter (for arabinonucleosides). Several examples of 2¡ä-C-Me-ribonucleosides showed moderate anti-HCV activities in a replicon assay accompanied by cytotoxicity. Several 7-hetaryl-7-deazaadenine fluoroarabino- and arabinonucleosides exerted moderate micromolar cytostatic effects. The most active was 7-ethynyl-7-deazaadenine fluoroarabinonucleoside which showed submicromolar antiproliferative activity. However, all the sugar-modified derivatives were less active than the parent ribonucleosides.