2',3'-O-isopropylidene-N6,N6'-dimethyladenosine | 19083-21-7

• 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',3'-O-isopropylidene-N6,N6'-dimethyladenosine
• 英文别名: O^2'_,O3'-isopropylidene-N⁶,N⁶-dimethyl-adenosine；O^2'_,O3'-Isopropyliden-N⁶,N⁶-dimethyl-adenosin；N6,N6-dimethyl-2',3'-O-isopropylideneadenosine；((3aR,4R,6R,6aR)-6-(6-(dimethylamino)-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol；[(3aR,4R,6R,6aR)-4-[6-(dimethylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol
• CAS: 19083-21-7
• 化学式: C₁₅H₂₁N₅O₄
• 分子量: 335.363
• InChiKey: VHDMVHZIKZHWEO-IDTAVKCVSA-N

物化性质

• 熔点：
  176-177 °C(Solv: ethanol (64-17-5))
• 沸点：
  539.2±60.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2',3'-O-isopropylidene-N6,N6'-dimethyladenosine 在 sodium hydride 、 氨基磺酰氯 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 16.5h， 以88%的产率得到2',3'-O-isopropylidene-5'-O-sulfamoyl-N6,N6'-dimethyladenosine
  参考文献：
  名称：

  用核苷双底物类似物抑制结核分枝杆菌中的铁载体生物合成：5'-O-[N-（水杨酰基）氨磺酰基]腺苷核碱基结构域的构效关系。

  摘要：

  5'-O-[N-(水杨基)氨磺酰基]腺苷 (Sal-AMS) 是一类新型抗结核药物的原型，可抑制参与分枝杆菌素生物合成的称为 MbtA 的芳酸腺苷酸化酶 (AAAE)。在此，我们报告了一系列全面系统的类似物的基于结构的设计、合成、生化和生物学评估，探索了 Sal-AMS 嘌呤核碱基结构域的构效关系。值得注意的是，2-苯基-Sal-AMS 衍生物 26 表现出异常有效的抗结核活性，在 0.049 microM 的缺铁条件下具有 MIC99，而 N-6-环丙基-Sal-AMS 16 导致提高的效力和 64-增强铁缺乏条件下相对于铁充足条件下的活性，与设计的作用机制一致的表型。

  DOI：

  10.1021/jm800567v
• 作为产物：
  描述：

  2’,3’,5’-三乙酰肌苷 在 4-二甲氨基吡啶 、 硫酸 、 氨 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.34h， 生成 2',3'-O-isopropylidene-N6,N6'-dimethyladenosine
  参考文献：
  名称：

  α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5′-Nucleotidase (CD73) Inhibitors

  摘要：

  ecto-5'-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor alpha,beta-methylene-ADP (AOPCP, adenosine-5'-O-[(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N-6-Monosubstitution was superior to symmetrical N-6,N-6-disubstitution. The most potent inhibitors were N-6-(4chlorobenzyl)-(10l, PSB-12441, K-i 7.23 n.M), N-6-phenylethyl(10h, PSB-12425, K-i 8.04 nM), and N-6-benzyl-adenosine-5'-O[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, K-i 9.03 nM). Replacement of the 6-NH group in 10g by 0 (10q, PSB-12431) or S (10r, PSB-12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 aM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nudeotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date.

  DOI：

  10.1021/acs.jmedchem.5b00802

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。
• Ribofuranose-ring cleavage of purine nucleosides with diisobutylaluminum hydride: Convenient method for the preparation of purine acyclonucleosides
  作者：Kosaku Hirota、Yasunari Monguchi、Yukio Kitade、Hironao Sajiki

  DOI：10.1016/s0040-4020(97)10098-9

  日期：1997.12

  The reaction of 2′,3′-O-isopropylidene protected purine nucleosides with diisobutylaluminum hydride (DIBAL-H) caused the reductive cleavage of the C-1′O-4′ bond to give the corresponding 9-d-ribitylpurines. The ring cleavage of inosine 1a, thioinosine 1f, and their derivatives having an alkyl group at the O6- or S6-position 1c,e, and g proceeded smoothly to afford the corresponding ribityl derivatives

  2'，3'- O-异亚丙基保护的嘌呤核苷与二异丁基氢化铝（DIBAL-H）的反应引起C-1'O-4'键的还原裂解，得到相应的9-d-核糖尿烷。肌苷1a，硫代肌苷1f及其在O 6或S 6位置1c，e和g具有烷基的衍生物的环裂解顺利进行，得到相应的核糖衍生物2a，f，c，e和g，而N 6-甲基化的腺苷衍生物1k和l显着抵抗了DIBAL-H的还原。5′-脱氧和5′-氯-5′-脱氧衍生物1b，d，i和j也在相似条件下在糖部分进行还原裂解。由鸟苷衍生物5以类似的方式制备了具有生物学意义的鸟苷6的无环类似物。合成嘌呤无环核苷的本方法学也被用于制备奈普兰霉素A的无环类似物17。
• Studies on compounds related to antitumor agents. Syntheses of 8-substituted N6,N6-dimethyladenosine derivatives.
  作者：TETSUO KATO、EITARO ARAKAWA、SHUICHI OGAWA、YASUKO SUZUMURA、TAKETOSHI KATO

  DOI：10.1248/cpb.34.3635

  日期：——

  N6, N6-Dimethyl-8-methylsulfonyladenosine, obtained from N6, N6-dimethyl-8-methylthioadenosine by highly selective oxidation with KMnO4, was treated with cyanide ion to give 8-cyano-N6, N6-dimethyladenosine. The conversion of the cyano group to methyl imidate, methoxycarbonyl, carbamoyl, carbothioamide, and carboxylic acid moieties was achieved. These 8-substituted N6, N6-dimethyladenosines may possess resonances structures involving positions 6 and 8 in adenosine, as indicated by the spectroscopic data. They showed no antitumor activity.

  N6, N6-二甲基-8-甲磺酰基腺苷是通过 KMnO4 高选择性氧化从 N6, N6-二甲基-8-甲硫基腺苷中得到的，用氰离子处理得到 8-氰基-N6, N6-二甲基腺苷。氰基可转化为亚胺酸甲酯、甲氧基羰基、氨基甲酰基、硫代磷酸甲酰胺和羧酸分子。光谱数据表明，这些 8-取代的 N6、N6-二甲基腺苷可能具有涉及腺苷中第 6 和第 8 位的共振结构。它们没有显示出抗肿瘤活性。
• Facile conversion of N6-benzoyladenosines into 5'-chloro-5'-deoxy-8-hydroxyadenosines by a reaction with cupric chloride: A prominent substituent effect of the N6-benzoyl group.
  作者：Yukio KITADE、Ryuji NAKANISHI、Magoichi SAKO、Kosaku HIROTA、Yoshifumi MAKI

  DOI：10.1248/cpb.39.1902

  日期：——

  Facile conversion of N6-benzoyl-2', 3'-O-isopropylideneadenosine (1) into N6-benzoyl-5'-chloro-5'-deoxy-8-hydroxy-2', 3'-O-isopropylideneadenosine (3) by a reaction with cupric chloride in acetonitrile provides a new method for the chemical modification of adenosines. This reflects the prominent substitutent effect of N6-benzoyl group on the chemical reactivity of adenosines.

  N6-苯甲酰基-2', 3'-O-异丙叉腺苷 (1) 轻松转化为 N6-苯甲酰基-5'-氯-5'-脱氧-8-羟基-2', 3'-O-异丙叉腺苷 (3)通过在乙腈中与氯化铜反应，为腺苷的化学修饰提供了一种新方法。这反映了N6-苯甲酰基对腺苷化学反应活性的显着取代作用。
• Modulators of Histone Methyltransferase, and Methods of Use Thereof
  申请人：Epizyme, Inc.

  公开号：US20160068559A1

  公开（公告）日：2016-03-10

  Disclosed are compounds, pharmaceutical compositions containing the compounds, and the uses of the compounds and compositions as modulators of histone methyltransferases, and for treating diseases influenced by modulation of histone methyltransferase activity.

  本发明涉及一种化合物、含有该化合物的药物组合物，以及将该化合物和组合物用作组蛋白甲基转移酶调节剂，以及治疗受组蛋白甲基转移酶活性调节影响的疾病的用途。