N⁶-(2-thienylmethyl)-9H-(3-C-methyl-β-D-ribofuranosyl)adenine | 1042976-46-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N⁶-(2-thienylmethyl)-9H-(3-C-methyl-β-D-ribofuranosyl)adenine
• 英文别名: (2R,3S,4R,5R)-2-(hydroxymethyl)-3-methyl-5-[6-(thiophen-2-ylmethylamino)purin-9-yl]oxolane-3,4-diol
• CAS: 1042976-46-4
• 化学式: C₁₆H₁₉N₅O₄S
• 分子量: 377.424
• InChiKey: XGBLLYJYONQDCZ-PDUOOLKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  154
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  在 氨 作用下， 以 甲醇 为溶剂， 生成 N⁶-(2-thienylmethyl)-9H-(3-C-methyl-β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  Ribose-Modified Purine Nucleosides as Ribonucleotide Reductase Inhibitors. Synthesis, Antitumor Activity, and Molecular Modeling of N⁶-Substituted 3′-C-Methyladenosine Derivatives

  摘要：

  A series of cycloalkyl, bicycloalkyl, aryl, and heteroaryl N-6-substituted derivatives of the antitumor agent 3'-C-methyladenosine (3'-Me-Ado), an inhibitor of the a Rnr1 subunit of mammalian ribonucleotide reductase (RR), were synthesized. The cytotoxicity of these compounds was evaluated against a panel of human leukemia and carcinoma cell lines and compared to that of some corresponding N6-substituted adenosine analogues. N-6-cycloalkyl-3'-C-methylribonucleosides 2-7 and N-6-phenyl analogue 8 were found to inhibit the proliferation of K562 leukemia cells. N6-(+/-)-endo-2-norbornyl-3'-C-methyladenosine (7) was found to be the most cytotoxic compound, with GI(50) values slightly higher than that of 3'-Me-Ado against K562 and carcinoma cell lines and 2.7 fold higher cytotoxicity against human promyelocytic leukemia HL-60 cells. The SAR study confirms that an unsubstituted N-6-amino group is essential for optimal cytotoxicity of 3'-Me-Ado against both K562 and carcinoma cell lines. Computational studies, carried out on the eukaryotic a subunit (Rnr1) of RR from Saccharomyces cerevisiae were performed to rationalize the observed structure-activity relationships.

  DOI：

  10.1021/jm800205c