2-chloro-N⁶,N⁶-dimethyladenosine | 13406-53-6

• 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: 2-chloro-N⁶,N⁶-dimethyladenosine
• 英文别名: 2-Chloro-N⁶-dimethyladenosine；(2R,3R,4S,5R)-2-(2-chloro-6-(dimethylamino)-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol；(2R,3R,4S,5R)-2-[2-chloro-6-(dimethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 13406-53-6
• 化学式: C₁₂H₁₆ClN₅O₄
• 分子量: 329.743
• InChiKey: CHFRYFONMULVBG-IOSLPCCCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-chloro-N⁶,N⁶-dimethyladenosine 在 吡啶 、 氯化亚砜 作用下， 以 乙腈 为溶剂， 反应 16.0h， 以79%的产率得到(2R,3R,4S,5S)-2-(2-chloro-6-(dimethylamino)-9H-purin-9-yl)-5-(chloromethyl)tetrahydrofuran-3,4-diol
  参考文献：
  名称：

  An efficient synthesis of base-substituted analogues of S-adenosyl-dl-homocysteine

  摘要：

  An efficient method for the preparation of base-substituted S-adenosyl-DL-homocysteine analogues as well as of 2-chloro-N-6-alkylated S-adenosyl-DL-homocysteine analogues is described. The method uses a convergent strategy that employs a common intermediate late in the overall synthesis and allows small libraries of SAH analogues to be prepared in a relatively short period of time. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.04.076
• 作为产物：
  描述：

  O⁶-(benzotriazol-1-yl)-2-chloro-9-[2,3,5-tri-O-(t-butyldimethylsilyl)-β-D-ribofuranosyl]purine 在 potassium fluoride 作用下， 以 甲醇 为溶剂， 反应 17.5h， 生成 2-chloro-N⁶,N⁶-dimethyladenosine
  参考文献：
  名称：

  Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides

  摘要：

  Cladribine（2-氯-2′-脱氧腺苷）是一种高效的临床应用核苷，用于治疗毛细胞白血病。它也正在针对其他淋巴恶性肿瘤进行评估，并且已引起人们关注超过半个世纪。为了继续我们对通过使用（苯并三唑-1-基）三（N,N-二甲氨基）磷镁六氟磷酸盐激活嘌呤核苷中的酰胺键的兴趣，我们评估了O6-(苯并三唑-1-基)-2′-脱氧鸟苷作为克拉利滨及其类似物的潜在前体。这些化合物在适当去保护后被评估其生物活性，数据在此呈现。针对毛细胞白血病（HCL）、T细胞淋巴瘤（TCL）和慢性淋巴细胞白血病（CLL），克拉利滨在三者中均表现出最高活性。克拉利滨的溴代类似物在HCL中表现出与克拉利滨的核糖代类似物相当的活性，但在TCL和CLL中活性更强。克拉利滨的溴代核糖类似物显示出活性，但在含有C6-NH2的化合物中活性最低。在外环氨基上的烷基取代似乎对活性有害，只有C6-哌啶基克拉利滨类似物表现出任何活性。针对腺癌MDA-MB-231细胞，克拉利滨及其核糖类似物表现出最高活性。

  DOI：

  10.3390/molecules201018437

文献信息

• Cladribine Analogues via O6-(Benzotriazolyl) Derivatives of Guanine Nucleosides
  作者：Sakilam Satishkumar、Prasanna Vuram、Siva Relangi、Venkateshwarlu Gurram、Hong Zhou、Robert Kreitman、Michelle Montemayor、Lijia Yang、Muralidharan Kaliyaperumal、Somesh Sharma、Narender Pottabathini、Mahesh Lakshman

  DOI：10.3390/molecules201018437

  日期：——

  Cladribine, 2-chloro-2′-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2′-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic leukemia (CLL), cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribose analogue of cladribine showed activity, but was the least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, cladribine and its ribose analogue were most active.

  Cladribine（2-氯-2′-脱氧腺苷）是一种高效的临床应用核苷，用于治疗毛细胞白血病。它也正在针对其他淋巴恶性肿瘤进行评估，并且已引起人们关注超过半个世纪。为了继续我们对通过使用（苯并三唑-1-基）三（N,N-二甲氨基）磷镁六氟磷酸盐激活嘌呤核苷中的酰胺键的兴趣，我们评估了O6-(苯并三唑-1-基)-2′-脱氧鸟苷作为克拉利滨及其类似物的潜在前体。这些化合物在适当去保护后被评估其生物活性，数据在此呈现。针对毛细胞白血病（HCL）、T细胞淋巴瘤（TCL）和慢性淋巴细胞白血病（CLL），克拉利滨在三者中均表现出最高活性。克拉利滨的溴代类似物在HCL中表现出与克拉利滨的核糖代类似物相当的活性，但在TCL和CLL中活性更强。克拉利滨的溴代核糖类似物显示出活性，但在含有C6-NH2的化合物中活性最低。在外环氨基上的烷基取代似乎对活性有害，只有C6-哌啶基克拉利滨类似物表现出任何活性。针对腺癌MDA-MB-231细胞，克拉利滨及其核糖类似物表现出最高活性。
• An efficient synthesis of base-substituted analogues of S-adenosyl-dl-homocysteine
  作者：David B. Llewellyn、Amal Wahhab

  DOI：10.1016/j.tetlet.2009.04.076

  日期：2009.7

  An efficient method for the preparation of base-substituted S-adenosyl-DL-homocysteine analogues as well as of 2-chloro-N-6-alkylated S-adenosyl-DL-homocysteine analogues is described. The method uses a convergent strategy that employs a common intermediate late in the overall synthesis and allows small libraries of SAH analogues to be prepared in a relatively short period of time. (C) 2009 Elsevier Ltd. All rights reserved.