6-chloro-9H-(2,3-di-O-acetyl-5-O-benzoyl-3-C-methyl-β-D-ribofuranosyl)purine | 849241-87-8

• 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: 6-chloro-9H-(2,3-di-O-acetyl-5-O-benzoyl-3-C-methyl-β-D-ribofuranosyl)purine
• 英文别名: 6-chloro-9H-(3-C-methyl-2,3-di-O-acetyl-5-O-benzoyl-β-D-ribofuranosyl)purine；6-chloro-(2,3-di-O-acetyl-5-O-benzoyl-3-C-methyl-β-D-ribofuranosyl)purine；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(6-chloropurin-9-yl)-3-methyloxolan-2-yl]methyl benzoate
• CAS: 849241-87-8
• 化学式: C₂₂H₂₁ClN₄O₇
• 分子量: 488.884
• InChiKey: YBKDZBITSDTIDH-WEMWZYORSA-N

物化性质

• 沸点：
  625.8±65.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  132
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  6-chloro-9H-(2,3-di-O-acetyl-5-O-benzoyl-3-C-methyl-β-D-ribofuranosyl)purine 在 氨 作用下， 反应 30.0h， 以97%的产率得到3'-C-Methyladenosine
  参考文献：
  名称：

  C-甲基-β-D-呋喃核糖基腺嘌呤核苷核糖核苷酸还原酶抑制剂的抗肿瘤活性。

  摘要：

  合成了一系列在核糖环的1'-，2'-或3'-位被甲基取代的腺苷衍生物，并评估了其抗肿瘤活性。通过这项研究，3'-C-甲基腺苷（3'-Me-Ado）作为最活跃的化合物出现，显示出对人骨髓性白血病K562，多药耐药性人白血病K562IU，人早幼粒细胞白血病HL-60，人结肠癌HT- 29和人类乳腺癌MCF-7细胞系，IC（50）值范围从11到38μM。结构-活性关系研究表明3'-Me-Ado的结构对于该活性至关重要。用小的烷基或环烷基取代N（6）-氨基的氢原子，在嘌呤环的2位引入氯原子，或甲基从3'位置移至其他核糖位置导致抗肿瘤活性降低或丧失。3'-Me-Ado的抗增殖活性似乎与其通过核糖核苷酸还原酶抑制作用同时耗尽细胞内嘌呤和嘧啶脱氧核苷酸的能力有关。

  DOI：

  10.1021/jm048944c
• 作为产物：
  描述：

  1,2,3-tri-O-acetyl-5-O-benzoyl-3-C-methyl-D-ribofuranose 、 6-氯嘌呤 在 三氟甲磺酸三甲基硅酯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以72%的产率得到6-chloro-9H-(2,3-di-O-acetyl-5-O-benzoyl-3-C-methyl-β-D-ribofuranosyl)purine
  参考文献：
  名称：

  C-甲基-β-D-呋喃核糖基腺嘌呤核苷核糖核苷酸还原酶抑制剂的抗肿瘤活性。

  摘要：

  合成了一系列在核糖环的1'-，2'-或3'-位被甲基取代的腺苷衍生物，并评估了其抗肿瘤活性。通过这项研究，3'-C-甲基腺苷（3'-Me-Ado）作为最活跃的化合物出现，显示出对人骨髓性白血病K562，多药耐药性人白血病K562IU，人早幼粒细胞白血病HL-60，人结肠癌HT- 29和人类乳腺癌MCF-7细胞系，IC（50）值范围从11到38μM。结构-活性关系研究表明3'-Me-Ado的结构对于该活性至关重要。用小的烷基或环烷基取代N（6）-氨基的氢原子，在嘌呤环的2位引入氯原子，或甲基从3'位置移至其他核糖位置导致抗肿瘤活性降低或丧失。3'-Me-Ado的抗增殖活性似乎与其通过核糖核苷酸还原酶抑制作用同时耗尽细胞内嘌呤和嘧啶脱氧核苷酸的能力有关。

  DOI：

  10.1021/jm048944c

文献信息

• Ribose-Modified Purine Nucleosides as Ribonucleotide Reductase Inhibitors. Synthesis, Antitumor Activity, and Molecular Modeling of <i>N</i>⁶-Substituted 3′-<i>C</i>-Methyladenosine Derivatives
  作者：Loredana Cappellacci、Palmarisa Franchetti、Patrizia Vita、Riccardo Petrelli、Antonio Lavecchia、Hiremagalur N. Jayaram、Philipp Saiko、Geraldine Graser、Thomas Szekeres、Mario Grifantini

  DOI：10.1021/jm800205c

  日期：2008.7.1

  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.
• Synthesis and biological activity of novel N6-substituted and 2,N6-disubstituted adenine ribo- and 3′-C-methyl-ribonucleosides as antitumor agents
  作者：Loredana Cappellacci、Riccardo Petrelli、Palmarisa Franchetti、Patrizia Vita、Praveen Kusumanchi、Mohineesh Kumar、Hiremagalur N. Jayaram、Bingsen Zhou、Yun Yen、Mario Grifantini

  DOI：10.1016/j.ejmech.2011.01.055

  日期：2011.5

  A series of N-6-aminopurine-9-beta-D-ribonucleosides and ribose-modified 3'-C-methyl analogues substituted at N-6-position with a small group like hydroxy, methoxy or amino group or at C2(N-6) position have been synthesized and tested against a panel of human leukemia and carcinoma cell lines. N-6-Hydrazino-9-beta-D-ribofuranosyl-Purine (5) displayed the best antiproliferative activity in the low micromolar or submicromolar range against all tested tumor cell lines. The activity of this nucleoside is related in part to ribonucleotide reductase inhibition. C2-modification or 3'-C-methylation in N-6-substituted adenosine analogues leads to a decrease or loss in activity. (C) 2011 Elsevier Masson SAS. All rights reserved.