6-N-cyclopropyl-9-(6,6-dibromo-5,6-dideoxy-2,3-O-isopropylidene-β-D-ribo-hex-5-enofuranosyl)adenine | 883743-41-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-N-cyclopropyl-9-(6,6-dibromo-5,6-dideoxy-2,3-O-isopropylidene-β-D-ribo-hex-5-enofuranosyl)adenine
• 英文别名: 9-[(3aR,4R,6R,6aR)-6-(2,2-dibromoethenyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-N-cyclopropylpurin-6-amine
• CAS: 883743-41-7
• 化学式: C₁₇H₁₉Br₂N₅O₃
• 分子量: 501.178
• InChiKey: LKHTYLRTJGAWHZ-RVXWVPLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  83.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-N-cyclopropyl-9-(6,6-dibromo-5,6-dideoxy-2,3-O-isopropylidene-β-D-ribo-hex-5-enofuranosyl)adenine 在 正丁基锂 、 三氟乙酸 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.33h， 生成 6-N-cyclopropyl-9-(5,6-dideoxy-β-D-ribo-hex-5-ynofuranosyl)adenine
  参考文献：
  名称：

  Antitrypanosomal Activity of 5‘-Deoxy-5‘-(iodomethylene)adenosine and Related 6-N-Cyclopropyladenosine Analogues

  摘要：

  Treatment of the 6-N-cyclopropyl-2',3'-di-O-isopropylideneadenosine 5'-aldehyde with sulfone-stabilized phosphonate or fluorophosphonate reagents followed by stannyldesulfonylations and subsequent iodo- or protiodestannylation gave 6-N-cyclopropyl-5'-deoxy-5'-(iodomethylene)adenosine 8b or its 5'-fluoromethylene analogue 11. Treatment of the 5'-aldehyde with hydroxylamine or dibromomethylene- or cyanomethylene-stabilized Wittig reagents and deprotections gave the oxime 4b, 5'-cyanomethylene 5b, and 5'-dibromomethylene 13b analogues. Dehydrobromination of 13b gave acetylenic compound 14b. From the tested 6-N-cyclopropyladenosine analogues modified at the 5' carbon, the 5'-iodomethylene 8b had the most potent activity against Trypanosoma brucei in vitro with an IC50 of 12 mu g/mL. The IC50 value was 19 mu g/mL for both the 5'-fluoromethylene 11 and the 5'-cyanomethylene 5b compounds. The (E)-5'-deoxy-5'-(iodomethylene)adenosine 2a, a known inhibitor of AdoHey hydrolase not modified with a cyclopropyl ring at 6-amino group, also inhibited T. brucei with an IC50 of 9 mu g/mL. In contrast to some other adenosine analogues modified at C5', the 6-N-cyclopropyladenosine analogues described here do not exhibit an inhibitory effect on AdoHcy hydrolase and displayed only marginal antiviral activity.

  DOI：

  10.1021/jm0511379
• 作为产物：
  描述：

  6-氯嘌呤核苷 在 二氯乙酸 、 对甲苯磺酸 、 二甲基亚砜 、 N,N'-二环己基碳二亚胺 、 三苯基膦 、 锌 作用下， 以 二氯甲烷 为溶剂， 反应 25.5h， 生成 6-N-cyclopropyl-9-(6,6-dibromo-5,6-dideoxy-2,3-O-isopropylidene-β-D-ribo-hex-5-enofuranosyl)adenine
  参考文献：
  名称：

  Antitrypanosomal Activity of 5‘-Deoxy-5‘-(iodomethylene)adenosine and Related 6-N-Cyclopropyladenosine Analogues

  摘要：

  Treatment of the 6-N-cyclopropyl-2',3'-di-O-isopropylideneadenosine 5'-aldehyde with sulfone-stabilized phosphonate or fluorophosphonate reagents followed by stannyldesulfonylations and subsequent iodo- or protiodestannylation gave 6-N-cyclopropyl-5'-deoxy-5'-(iodomethylene)adenosine 8b or its 5'-fluoromethylene analogue 11. Treatment of the 5'-aldehyde with hydroxylamine or dibromomethylene- or cyanomethylene-stabilized Wittig reagents and deprotections gave the oxime 4b, 5'-cyanomethylene 5b, and 5'-dibromomethylene 13b analogues. Dehydrobromination of 13b gave acetylenic compound 14b. From the tested 6-N-cyclopropyladenosine analogues modified at the 5' carbon, the 5'-iodomethylene 8b had the most potent activity against Trypanosoma brucei in vitro with an IC50 of 12 mu g/mL. The IC50 value was 19 mu g/mL for both the 5'-fluoromethylene 11 and the 5'-cyanomethylene 5b compounds. The (E)-5'-deoxy-5'-(iodomethylene)adenosine 2a, a known inhibitor of AdoHey hydrolase not modified with a cyclopropyl ring at 6-amino group, also inhibited T. brucei with an IC50 of 9 mu g/mL. In contrast to some other adenosine analogues modified at C5', the 6-N-cyclopropyladenosine analogues described here do not exhibit an inhibitory effect on AdoHcy hydrolase and displayed only marginal antiviral activity.

  DOI：

  10.1021/jm0511379

文献信息

• Antitrypanosomal Activity of 5‘-Deoxy-5‘-(iodomethylene)adenosine and Related 6-<i>N</i>-Cyclopropyladenosine Analogues
  作者：Magdalena Rapp、Trisha A. Haubrich、Jacques Perrault、Zachary B. Mackey、James H. McKerrow、Peter K. Chiang、Stanislaw F. Wnuk

  DOI：10.1021/jm0511379

  日期：2006.3.1

  Treatment of the 6-N-cyclopropyl-2',3'-di-O-isopropylideneadenosine 5'-aldehyde with sulfone-stabilized phosphonate or fluorophosphonate reagents followed by stannyldesulfonylations and subsequent iodo- or protiodestannylation gave 6-N-cyclopropyl-5'-deoxy-5'-(iodomethylene)adenosine 8b or its 5'-fluoromethylene analogue 11. Treatment of the 5'-aldehyde with hydroxylamine or dibromomethylene- or cyanomethylene-stabilized Wittig reagents and deprotections gave the oxime 4b, 5'-cyanomethylene 5b, and 5'-dibromomethylene 13b analogues. Dehydrobromination of 13b gave acetylenic compound 14b. From the tested 6-N-cyclopropyladenosine analogues modified at the 5' carbon, the 5'-iodomethylene 8b had the most potent activity against Trypanosoma brucei in vitro with an IC50 of 12 mu g/mL. The IC50 value was 19 mu g/mL for both the 5'-fluoromethylene 11 and the 5'-cyanomethylene 5b compounds. The (E)-5'-deoxy-5'-(iodomethylene)adenosine 2a, a known inhibitor of AdoHey hydrolase not modified with a cyclopropyl ring at 6-amino group, also inhibited T. brucei with an IC50 of 9 mu g/mL. In contrast to some other adenosine analogues modified at C5', the 6-N-cyclopropyladenosine analogues described here do not exhibit an inhibitory effect on AdoHcy hydrolase and displayed only marginal antiviral activity.