2-iodo-6-chloro-9-(β-D-ribofuranosyl)purine | 313477-85-9

• 物质功能分类: 生物化工 - 核苷类药物
• 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-iodo-6-chloro-9-(β-D-ribofuranosyl)purine
• 英文别名: 6-chloro-2-iodopurine 9-riboside；6-Chloro-2-iodopurine riboside；(2R,3R,4S,5R)-2-(6-chloro-2-iodopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 313477-85-9
• 化学式: C₁₀H₁₀ClIN₄O₄
• 分子量: 412.571
• InChiKey: BUXRSMOYQZICAU-UUOKFMHZSA-N

物化性质

• 沸点：
  715.7±70.0 °C(Predicted)
• 密度：
  2.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-iodo-6-chloro-9-(β-D-ribofuranosyl)purine 在 氨 作用下， 反应 18.0h， 以94%的产率得到2-碘腺苷
  参考文献：
  名称：

  Adenosine Analogues as Inhibitors of Trypanosoma brucei Phosphoglycerate Kinase:  Elucidation of a Novel Binding Mode for a 2-Amino-N⁶-Substituted Adenosine

  摘要：

  As part of a project aimed at structure-based design of adenosine analogues as drugs against African trypanosomiasis, N-6-, 2-amino-N-6-, and N-2-substituted adenosine analogues were synthesized and tested to establish structure-activity relationships for inhibiting Trypanosoma brucei glycosomal phosphoglycerate kinase (PGK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and glycerol-3-phosphate dehydrogenase (GPDH). Evaluation of X-ray structures of parasite PGK, GAPDH, and GPDH complexed with their adenosyl-bearing substrates led us to generate a series of adenosine analogues which would target all three enzymes simultaneously. There was a modest preference by PGK for NG-substituted analogues bearing the 2-amino group. The best compound in this series, 2-amino-N-6-[2 "-(p-hydroxyphenyl)ethyl]adenosine (46b), displayed a 23-fold improvement over adenosine with an IC50 of 130 muM. 2-[[2 "-(p-Hydroxyphenyl)ethyl]amino]adenosine (46c) was a weak inhibitor of T. brucei PGK with an IC50 of 500 muM. To explore the potential of an additive effect that having the N-6 and N-2 substitutions in one molecule might provide, the best ligands from the two series were incorporated into N-6,N-2-disubstituted adenosine analogues to yield N-6-(2 " -phenylethyl)-2-[(2 " -phenylethyl)amino]adenosine (69) as a 30 muM inhibitor of T. brucei PGK which is 100-fold more potent than the adenosine template. In contrast, these series gave no compounds that inhibited parasitic GAPDH or GPDH more than 10-20% when tested at 1.0 mM. A 3.0 Angstrom X-ray structure of a T, brucei PGK/46b complex revealed a binding mode in which the nucleoside analogue was flipped and the ribosyl moiety adopted a syn conformation as compared with the previously determined binding mode of ADP. Molecular docking experiments using QXP and SAS program suites reproduced this "flipped and rotated" binding mode.

  DOI：

  10.1021/jm000287a
• 作为产物：
  描述：

  6-氯鸟嘌呤核苷 在 copper(l) iodide 、 二碘甲烷 、 碘 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以46.5%的产率得到2-iodo-6-chloro-9-(β-D-ribofuranosyl)purine
  参考文献：
  名称：

  [EN] ADENOSINE ANALOGS FOR THE TREATMENT OF DISEASE
  [FR] ANALOGUES D'ADÉNOSINE POUR LE TRAITEMENT D'UNE MALADIE

  摘要：

  该披露提供了用于治疗疾病，如疼痛和炎症症状的腺苷类似物。

  公开号：

  WO2020247546A1

文献信息

• Substituted 6-(Benzylamino) Purine Riboside Derivatives, Use Thereof and Compositions Containing These Derivatives
  申请人：Szucova Lucie

  公开号：US20120071433A1

  公开（公告）日：2012-03-22

  The invention relates to 2-substituted-6-(substituted benzylamino)purine riboside derivatives of the general formula I. These compounds possess antiapoptotic, anti-inflammatory and differentiating activities. The invention relates also to the compositions, which contain these derivatives as active ingredients.

  该发明涉及一般式I的2-取代-6-(取代苯基氨基)嘌呤核苷衍生物。这些化合物具有抗凋亡、抗炎和分化活性。该发明还涉及包含这些衍生物作为活性成分的组合物。
• [EN] SUBSTITUTED 6-(BENZYLAMINO) PURINE RIBOSIDE DERIVATIVES, USE THEREOF AND COMPOSITIONS CONTAINING THESE DERIVATIVES<br/>[FR] DÉRIVÉS DE RIBOSIDE DE 6-BENZYLAMINOPURINE SUBSTITUÉE, LEURS UTILISATIONS ET COMPOSITIONS CONTENANT CES DÉRIVÉS
  申请人：UNIVERZITA PALACKEHO V OLOMOUC

  公开号：WO2010130233A1

  公开（公告）日：2010-11-18

  The invention relates to 2-substituted-6-(substituted benzylamino)purine riboside derivatives of the general formula I. These compounds possess antiapoptotic, anti-inflammatory and differentiating activities. The invention relates also to the compositions, which contain these derivatives as active ingredients. ˙

  该发明涉及一般式I的2-取代-6-(取代苄胺基)嘌呤核苷衍生物。这些化合物具有抗凋亡、抗炎和分化活性。该发明还涉及含有这些衍生物作为活性成分的组合物。
• Scaffold Repurposing of Nucleosides (Adenosine Receptor Agonists): Enhanced Activity at the Human Dopamine and Norepinephrine Sodium Symporters
  作者：Dilip K. Tosh、Aaron Janowsky、Amy J. Eshleman、Eugene Warnick、Zhan-Guo Gao、Zhoumou Chen、Elizabeth Gizewski、John A. Auchampach、Daniela Salvemini、Kenneth A. Jacobson

  DOI：10.1021/acs.jmedchem.7b00141

  日期：2017.4.13

  At DAT, the binding of two structurally dissimilar radioligands was enhanced; NET binding of only one radioligand was enhanced; SERT radioligand binding was minimally affected. 10 was more potent than cocaine at inhibiting DA uptake (IC50 = 107 nM). Ribose analogues were weaker in DAT interaction than the corresponding bicyclics. Thus, we enhanced the neurotransmitter transporter activity of rigid nucleosides

  我们重新调整了 (N)-methanocarba 腺苷衍生物（A3 腺苷受体 (AR) 激动剂）的用途，以增强放射性配体在人多巴胺 (DA) 转运蛋白 (DAT) 上的变构结合并抑制 DA 摄取。我们通过小N6-烷基取代、5'-酯、腺嘌呤的脱氮修饰以及恢复核糖代替甲烷碳，扩展了该系列的结构-活性关系。 C2-(5-卤代-2-基)-乙炔基 5'-甲基 9 (MRS7292) 和 5'-乙基 10 (MRS7232) 酯增强 DAT (EC50 ∼ 35 nM) 和去甲肾上腺素转运蛋白 (NET) 的结合。与 A3AR 相比，9 和 10 在小鼠中对 DAT 具有选择性，但在人类中则不然。在 DAT 中，两种结构不同的放射性配体的结合得到增强；仅一种放射性配体的 NET 结合得到增强； SERT 放射性配体结合受到的影响最小。 10 在抑制 DA 摄取方面比可卡因更有效 (IC50 = 107
• ABCA-1 ELEVATING COMPOUNDS AND METHODS
  申请人：Dhalla Arvinder

  公开号：US20090203689A1

  公开（公告）日：2009-08-13

  Disclosed are novel compounds of Formula I useful for treating various disease states, in particular, insulin resistance, diabetes, dyslipidemia, coronary artery disease, and inflammation. The compounds of the present invention elevate cellular expression of the ABCA-1 gene as well as increasing the level of ABCA-1 protein, which may result in an increase in HDL levels in the plasma of a mammal, in particular humans.

  本发明公开了一种公式I的新化合物，用于治疗各种疾病状态，特别是胰岛素抵抗、糖尿病、血脂异常、冠状动脉疾病和炎症。本发明的化合物提高了ABCA-1基因的细胞表达，同时增加了ABCA-1蛋白的水平，这可能导致哺乳动物，特别是人类血浆中HDL水平的增加。
• Partial and full agonists of A1 adenosine receptors
  申请人：Dhalla Arvinder

  公开号：US20070185051A1

  公开（公告）日：2007-08-09

  Disclosed are novel compounds a compound of Formula I that are partial and full A 1 adenosine receptor agonists, useful for treating various disease states, in particular dyslipidemia, diabetes, decreased insulin sensitivity, Polycystic Ovarian Syndrome, Stein-Leventhal syndrome, and obesity.

  本发明涉及一种新型化合物，其中化合物I的部分和全A1腺苷受体激动剂，可用于治疗各种疾病状态，特别是血脂异常、糖尿病、胰岛素敏感性降低、多囊卵巢综合征、斯坦-莱文塔尔综合征和肥胖症。