2-[(6-Aminopurin-9-yl)methoxy]ethyl sulfamate | 75128-52-8

• 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: 2-[(6-Aminopurin-9-yl)methoxy]ethyl sulfamate
• CAS: 75128-52-8
• 化学式: C₈H₁₂N₆O₄S
• 分子量: 288.287
• InChiKey: BGUQVFPTNOCVHL-UHFFFAOYSA-N

物化性质

• 沸点：
  591.5±60.0 °C(Predicted)
• 密度：
  1.84±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  157
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-[(6-Aminopurin-9-yl)methoxy]ethyl sulfamate 、 N-hydroxysuccinimidyl 2-benzyloxybenzoate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 9-{[({N-[2-(benzyloxy)benzoyl]sulfamoyl}-oxy)ethoxy]methyl}adenine
  参考文献：
  名称：

  Antitubercular Nucleosides That Inhibit Siderophore Biosynthesis:  SAR of the Glycosyl Domain

  摘要：

  Tuberculosis is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure-activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a K-I(app) value of 2.3 nM and MIC99 values of 1.56 mu M against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a transporter for entry across the mycobacterial cell envelope. Additionally, we report improved conditions for the expression of MbtA and biochemical analysis, demonstrating that MbtA follows a random sequential enzyme mechanism for the adenylation half-reaction.

  DOI：

  10.1021/jm061068d
• 作为产物：
  描述：

  1-[(2-羟基乙氧基)甲基]腺嘌呤 在 氨基磺酰氯 、 sodium hydride 作用下， 生成 2-[(6-Aminopurin-9-yl)methoxy]ethyl sulfamate
  参考文献：
  名称：

  5'-氨磺酰化嘌呤基碳环核苷的合成及生物学评价。

  摘要：

  合成了第一批5'-磺酰化碳环嘌呤核苷，并测试了其抗肿瘤和抗菌活性。通过使2'，3'-丙酮化物保护的碳环核苷与氨磺酰氯反应，然后脱保护，形成目标化合物。测试了这些药剂对P388小鼠白血病细胞的细胞毒活性。5'-氨磺酰基碳环腺苷（2）和5-氨磺酰基-8-氮杂碳环腺苷（6）这两种化合物的IC50值分别低至62和15 nM。这些类似物抑制了P388细胞的蛋白质生物合成，并减慢了DNA和RNA的生物合成。没有一种靶标分子对大肠埃希氏菌具有如此强的抗肿瘤细胞效用。另外，在无细胞系统中 试剂2和6在兔网织红细胞裂解物中比在大肠杆菌中是更有效的蛋白质合成抑制剂。这些新的碳环衍生物在影响翻译中似乎比真核细胞对真核细胞具有一定的选择性。

  DOI：

  10.1021/jm00100a003

文献信息

• Antibacterial Agents
  申请人：Aldrich Courtney

  公开号：US20080293666A1

  公开（公告）日：2008-11-27

  The invention provides compounds of formula (I) and salts thereof: R 1 -L-R 2 —B wherein R 1 , L, R 2 , and B have any of the values defined herein, as well as compositions comprising such compounds, and therapeutic methods comprising the administration of such compounds or salts. The compounds block siderophore production in bacteria and are useful as antibacterial agents.

  这项发明提供了化合物的公式(I)及其盐：R1-L-R2—B，其中R1、L、R2和B具有本文中定义的任何值，以及包含这种化合物的组合物，以及包含这种化合物或盐的治疗方法。这些化合物可以阻断细菌中的铁载体产生，并可用作抗菌剂。
• Synthesis and biological evaluation of 5'-sulfamoylated purinyl carbocyclic nucleosides
  作者：Eileen M. Peterson、Jay Brownell、Robert Vince

  DOI：10.1021/jm00100a003

  日期：1992.10

  series of 5'-sulfamoylated carbocyclic purinyl nucleosides was synthesized and tested for antitumor and antibacterial activities. The target compounds were formed by reacting the 2',3'-acetonide-protected carbocyclic nucleosides with sulfamoyl chloride, followed by deprotection. The agents were tested for cytotoxic activity against P388 mouse leukemia cells. Two compounds, 5'-sulfamoyl carbocyclic adenosine

  合成了第一批5'-磺酰化碳环嘌呤核苷，并测试了其抗肿瘤和抗菌活性。通过使2'，3'-丙酮化物保护的碳环核苷与氨磺酰氯反应，然后脱保护，形成目标化合物。测试了这些药剂对P388小鼠白血病细胞的细胞毒活性。5'-氨磺酰基碳环腺苷（2）和5-氨磺酰基-8-氮杂碳环腺苷（6）这两种化合物的IC50值分别低至62和15 nM。这些类似物抑制了P388细胞的蛋白质生物合成，并减慢了DNA和RNA的生物合成。没有一种靶标分子对大肠埃希氏菌具有如此强的抗肿瘤细胞效用。另外，在无细胞系统中 试剂2和6在兔网织红细胞裂解物中比在大肠杆菌中是更有效的蛋白质合成抑制剂。这些新的碳环衍生物在影响翻译中似乎比真核细胞对真核细胞具有一定的选择性。
• US7989430B2
  申请人：——

  公开号：US7989430B2

  公开（公告）日：2011-08-02
• [EN] ANTIBACTERIAL AGENTS<br/>[FR] AGENTS ANTIBACTERIENS
  申请人：UNIV MINNESOTA

  公开号：WO2007067559A2

  公开（公告）日：2007-06-14

  [EN] The invention provides compounds of formula (I) and salts thereof: R₁-L-R₂-B wherein R₁, L, R₂, and B have any of the values defined herein, as well as compositions comprising such compounds, and therapeutic methods comprising the administration of such compounds or salts. The compounds block siderophore production in bacteria and are useful as antibacterial agents.
  [FR] La présente invention concerne des composés de formule (I) et des sels de ceux-ci : R₁-L-R₂-B où R₁, L, R₂, et B ont l'une quelconque des valeurs définies dans la présente, ainsi que des compositions comprenant de tels composés, et des procédés thérapeutiques comprenant l'administration de tels composés ou sels. Les composés bloquent la production de sidérophore dans des bactéries et sont utiles en tant qu'agents antibactériens.
• Antitubercular Nucleosides That Inhibit Siderophore Biosynthesis:  SAR of the Glycosyl Domain
  作者：Ravindranadh V. Somu、Daniel J. Wilson、Eric M. Bennett、Helena I. Boshoff、Laura Celia、Brian J. Beck、Clifton E. Barry、Courtney C. Aldrich

  DOI：10.1021/jm061068d

  日期：2006.12.1

  Tuberculosis is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure-activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a K-I(app) value of 2.3 nM and MIC99 values of 1.56 mu M against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a transporter for entry across the mycobacterial cell envelope. Additionally, we report improved conditions for the expression of MbtA and biochemical analysis, demonstrating that MbtA follows a random sequential enzyme mechanism for the adenylation half-reaction.