tert-butyl (9-((3aR,4R,6R,6aR)-6-(azidomethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-yl)carbamate | 873556-44-6

• 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: tert-butyl (9-((3aR,4R,6R,6aR)-6-(azidomethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-yl)carbamate
• 英文别名: tert-butyl N-[9-[(3aR,4R,6R,6aR)-6-(azidomethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]purin-6-yl]carbamate
• CAS: 873556-44-6
• 化学式: C₁₈H₂₄N₈O₅
• 分子量: 432.439
• InChiKey: TYYPFRWYSFJSGZ-SDBHATRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl (9-((3aR,4R,6R,6aR)-6-(azidomethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-yl)carbamate 在 palladium on activated charcoal 氨基磺酰氯 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 40.0h， 生成 tert-butyl 9-(((3aR,4R,6R,6aR)-2,2-dimethyl-6-((sulfamoylamino)methyl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-yl)carbamate
  参考文献：
  名称：

  Rationally Designed Nucleoside Antibiotics That Inhibit Siderophore Biosynthesis of Mycobacterium tuberculosis

  摘要：

  A rationally designed nucleoside inhibitor of Mycobacterium tuberculosis growth (MIC99 = 0.19 mu M) that disrupts siderophore biosynthesis was identified. The activity is due to inhibition of the adenylate-forming enzyme MbtA which is involved in biosynthesis of the mycobactins.

  DOI：

  10.1021/jm051060o
• 作为产物：
  描述：

  2',3'-异丙叉腺苷 在 叠氮磷酸二苯酯 、 sodium hydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 mineral oil 为溶剂， 反应 24.75h， 生成 tert-butyl (9-((3aR,4R,6R,6aR)-6-(azidomethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-yl)carbamate
  参考文献：
  名称：

  [EN] NOVEL HISTONE METHYLTRANSFERASE INHIBITORS
  [FR] NOUVEAUX INHIBITEURS D'HISTONE MÉTHYLTRANSFÉRASES

  摘要：

  本发明涉及式(I)定义的新的化合物。这些化合物是七-β-链家族组蛋白甲基转移酶的抑制剂，特别是KMT9的抑制剂。

  公开号：

  WO2021053158A1

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。
• 5‘-<i>O</i>-[(<i>N</i>-Acyl)sulfamoyl]adenosines as Antitubercular Agents that Inhibit MbtA:  An Adenylation Enzyme Required for Siderophore Biosynthesis of the Mycobactins
  作者：Chunhua Qiao、Amol Gupte、Helena I. Boshoff、Daniel J. Wilson、Eric M. Bennett、Ravindranadh V. Somu、Clifton E. Barry、Courtney C. Aldrich

  DOI：10.1021/jm070905o

  日期：2007.11.1

  A study of the structure-activity relationships of 5'-O-[N-(salicyl)sulfamoyl]adenosine (6), a potent inhibitor of the bifunctional enzyme salicyl-AMP ligase (MbtA, encoded by the gene Rv2384) in Mycobacterium tuberculosis, is described, targeting the salicyl moiety. A systematic series of analogues was prepared exploring the importance of substitution at the C-2 position revealing that a hydroxy group

  5'-O-[N-(水杨酰基)氨磺酰基]腺苷 (6) 的构效关系研究，这是一种双功能酶水杨酰-AMP 连接酶（MbtA，由基因 Rv2384 编码）在结核分枝杆菌中的有效抑制剂，描述，靶向水杨酸部分。制备了一系列系统的类似物，探索在 C-2 位置取代的重要性，揭示最佳活性需要羟基。对一系列取代的水杨基衍生物的检查表明，在 C-4 处的取代是可以容忍的。因此，该位置的一系列类似物提供了 4-氟衍生物，在铁限制条件下，其对全细胞结核分枝杆菌的 MIC99 为 0.098 microM，令人印象深刻。其他杂环、环烷基、烷基、
• Mechanism-based inhibitors of MenE, an acyl-CoA synthetase involved in bacterial menaquinone biosynthesis
  作者：Xuequan Lu、Huaning Zhang、Peter J. Tonge、Derek S. Tan

  DOI：10.1016/j.bmcl.2008.07.130

  日期：2008.11

  Menaquinone (vitamin K(2)) is an essential component of the electron transfer chain in many pathogens, including Mycobacterium tuberculosis and Staphylococcus aureus, and menaquinone biosynthesis is a potential target for antibiotic drug discovery. We report herein a series of mechanism-based inhibitors of MenE, an acyl-CoA synthetase that catalyzes adenylation and thioesterification of o-succinylbenzoic

  甲萘醌（维生素 K(2)）是许多病原体（包括结核分枝杆菌和金黄色葡萄球菌）中电子传递链的重要组成部分，甲萘醌生物合成是抗生素药物发现的潜在目标。我们在此报告了一系列基于机制的 MenE 抑制剂，MenE 是一种酰基辅酶 A 合成酶，可在甲基萘醌生物合成过程中催化邻琥珀酰苯甲酸 (OSB) 的腺苷酸化和硫酯化。最有效的化合物以 5.7microM 的 IC(50) 值抑制 MenE。
• A Mechanism-Based Aryl Carrier Protein/Thiolation Domain Affinity Probe
  作者：Chunhua Qiao、Daniel J. Wilson、Eric M. Bennett、Courtney C. Aldrich

  DOI：10.1021/ja069201e

  日期：2007.5.1

  The design, synthesis, and biochemical characterization of a mechanism-based aryl carrier protein (ArCP) affinity probe that selectively modifies the terminal thiol of the aryl carrier protein phosphopantetheine (Ppant) prosthetic group is described. Labeling of the aryl carrier protein was shown to require the cognate adenylating enzyme to channel the affinity probe onto the Ppant cofactor. The selective labeling was established by observation of the phosphopantetheinyl ejection ion via MS/MS, and the probe was also found to stabilize an interaction between an aryl carrier protein and adenylating enzyme by an electrophoretic mobility shift assay.
• [EN] SPECIFIC SMALL MOLECULE INHIBITORS THAT BLOCK KMT9 METHYLTRANSFERASE ACTIVITY AND FUNCTION<br/>[FR] INHIBITEURS À PETITES MOLÉCULES SPÉCIFIQUES QUI BLOQUENT L'ACTIVITÉ ET LA FONCTION DE LA MÉTHYLTRANSFÉRASE KMT9
  申请人：[en]ALBERT-LUDWIGS-UNIVERSITÄT FREIBURG

  公开号：WO2023017152A1

  公开（公告）日：2023-02-16

  The present invention relates to novel specific small molecule inhibitors that block KMT9 methyltransferase activity. In particular, the present invention is concerned with a compound of formula (I) wherein X1, X2, X3, X4, R1, R2, R3, R5, R6and L are as defined herein. Further, the present invention is concerned with a pharmaceutical composition comprising a pharmaceutically effective amount of the compound of formula (I). The present invention also relates to a compound of formula (I) and a pharmaceutical composition comprising a compound of formula (I) for use in medicine. Yet further, the present invention is concerned with a compound of formula (I) and a pharmaceutical composition comprising a compound of formula (I) for use as inhibitor of KMT9. Finally, the present invention is concerned with a compound of formula (I), wherein X1, X2, X3, X4, R1, R2, R3, R5, R6and L are as defined herein, for use in the treatment of cancer selected from the group as defined herein.