9-{(2R,3R,4S,5S)-3-azido-4-{[tert-butyl(dimethyl)silyl]oxy}-5-[(methylthio)methyl]tetrahydrofuran-2-yl}-9H-purin-6-amine | 595608-36-9

• 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: 9-{(2R,3R,4S,5S)-3-azido-4-{[tert-butyl(dimethyl)silyl]oxy}-5-[(methylthio)methyl]tetrahydrofuran-2-yl}-9H-purin-6-amine
• 英文别名: 9-[(2R,3R,4S,5S)-3-azido-4-[tert-butyl(dimethyl)silyl]oxy-5-(methylsulfanylmethyl)oxolan-2-yl]purin-6-amine
• CAS: 595608-36-9
• 化学式: C₁₇H₂₈N₈O₂SSi
• 分子量: 436.613
• InChiKey: JXTIQIFDZHUZRA-QQHRNGFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.74
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  9-{(2R,3R,4S,5S)-3-azido-4-{[tert-butyl(dimethyl)silyl]oxy}-5-[(methylthio)methyl]tetrahydrofuran-2-yl}-9H-purin-6-amine 在 tert-butyl-ammonium fluoride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 (2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-azido-2-[(methylthio)methyl]tetrahydrofuran-3-ol
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel human 5′-deoxy-5′-methylthioadenosine phosphorylase (MTAP) substrates

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of novel MTAP substrates are described. These compounds incorporate various C5'-moieties and are shown to have different k(cat)/K values compared with the natural MTAP substrate (MTA). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.107
• 作为产物：
  描述：

  在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 9-{(2R,3R,4S,5S)-3-azido-4-{[tert-butyl(dimethyl)silyl]oxy}-5-[(methylthio)methyl]tetrahydrofuran-2-yl}-9H-purin-6-amine
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of novel human 5′-deoxy-5′-methylthioadenosine phosphorylase (MTAP) substrates

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of novel MTAP substrates are described. These compounds incorporate various C5'-moieties and are shown to have different k(cat)/K values compared with the natural MTAP substrate (MTA). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.107

文献信息

• Combination therapies for treating methylthioadenosine phosphorylase deficient cells
  申请人：——

  公开号：US20040043959A1

  公开（公告）日：2004-03-04

  The present invention is directed to combination therapies for treating cell proliferative disorders associated with methylthioadenosine phosphorylase (MTAP) deficient cells in a mammal. The combination therapies selectively kill MTAP-deficient cells by administering an inhibitor of de novo inosinate synthesis and administering an anti-toxicity agent, wherein the inhibitors of de novo inosinate synthesis are inhibitors of glycinamide ribonucleotide formyltransferase (“GARFT”) and/or aminoinidazolecarboximide ribonucleotide formyltransferase (“AICARFT”), and the anti-toxicity agent is an MTAP substrate (e.g. methylthioadenosine or “MTA”), a precursor of MTA, an analog of an MTA precursor or a prodrug of an MTAP substrate.

  本发明涉及用于治疗哺乳动物中与甲基硫腺苷磷酸化酶（MTAP）缺乏细胞相关的细胞增殖性疾病的联合疗法。该联合疗法通过给予新生核苷酸合成抑制剂和给予抗毒性剂，选择性地杀死MTAP缺乏细胞，其中，新生核苷酸合成抑制剂是甘氨酰核苷酸甲酰转移酶（“GARFT”）和/或氨基咪唑羧酰核苷酸甲酰转移酶（“AICARFT”）的抑制剂，抗毒性剂是MTAP底物（例如，甲基硫腺苷或“MTA”），MTA的前体，MTA前体的类似物或MTAP底物的前药。