6-氯-9-(2,3,5-三苯甲酰氧基-2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤 | 205171-04-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 6-氯-9-(2,3,5-三苯甲酰氧基-2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤
• 英文名称: (2R,3R,4R,5R)-5-((benzoyloxy)methyl)-2-(6-chloro-9H-purin-9-yl)-3-methyltetrahydrofuran-3,4-diyl dibenzoate
• 英文别名: 6-chloro-9-(2-C-methyl-2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-9H-purine；6-chloro-9H-(2-C-methyl-2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)purine；6-chloro-9H-(2-C-methyl-2,3,5-O-benzoyl-β-D-ribofuranosyl)purine；(2R,3R,4R,5R)-5-[(benzoyloxy)methyl]-2-(6-chloro-9H-purin-9-yl)-3-methyltetrahydrofuran-3,4-diyl dibenzoate；6-chloro-9-(2',3',5'-tri-O-benzoyl-2'-methyl-β-D-ribofuranosyl)purine；6-Chloro-9-(2,3,5-tri-O-benzoyl-2-C-methyl-beta-D-ribofuranosyl)-9H-purine；[(2R,3R,4R,5R)-3,4-dibenzoyloxy-5-(6-chloropurin-9-yl)-4-methyloxolan-2-yl]methyl benzoate
• CAS: 205171-04-6
• 化学式: C₃₂H₂₅ClN₄O₇
• 分子量: 613.026
• InChiKey: LSZDBTSFULCQHJ-KHWZNAFNSA-N

物化性质

• 沸点：
  757.0±70.0 °C(Predicted)
• 密度：
  1.41

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  132
• 氢给体数：
  0
• 氢受体数：
  10

制备方法与用途

6-氯-9-(2,3,5-三-O-苯甲酰基-2-甲基-β-D-呋喃核糖基)-9H-嘌呤二苯甲酸酯是一种嘌呤核苷类似物，具有广泛的抗肿瘤活性，尤其针对惰性淋巴系统恶性肿瘤。其抗癌机制主要依赖于抑制DNA合成和诱导细胞凋亡等过程。

反应信息

• 作为反应物：
  描述：

  6-氯-9-(2,3,5-三苯甲酰氧基-2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤 在 chromium(VI) oxide 、 氯化亚砜 、 硫酸 、 氨 、 对甲苯磺酸 、 三乙胺 、 原甲酸三乙酯 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 108.0h， 生成 (3aR,4S,6R,6aR)-6-[6-(3-Iodo-benzylamino)-purin-9-yl]-2,2,6a-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  2‘-C-Methyl Analogues of Selective Adenosine Receptor Agonists:  Synthesis and Binding Studies

  摘要：

  2'-C-Methyl analogues of selective adenosine receptor agonists such as (R)-PIA, CPA, CCPA, NECA, and IB-MECA were synthesized in order to further investigate the subdomain that binds the ribose moiety. Binding affinities of these new compounds at A(1) and A(2A) receptors in bovine brain membranes and at A(3) in rat testis membranes were determined and compared. It was found that the 2'-C-methyl modification resulted in a decrease of the affinity, particularly at A(2A) and A(3) receptors. When such modification was combined with N-6-substitutions with groups which induce high potency and selectivity at Al receptors, the high affinity was retained and the selectivity was increased. Thus, 2-chloro-2'-C-methyl-N-6-cyclopentyladenosine (2'-Me-CCPA), which displayed a K-i value of 1.8 nM at A(1) receptors, was selective for A(1) vs A(2A) and A(3) receptors by 2166- and 2777-fold, respectively, resulting in one of the most potent and A(1)-selective agonists so far known. In functional assay, this compound inhibited forskolin-stimulated adenylyl cyclase activity with an IC50 value of 13.1 nM, acting as a full agonist.

  DOI：

  10.1021/jm9707737
• 作为产物：
  描述：

  1,3,5-三苯甲酰基-D-呋喃核糖 在 4-二甲氨基吡啶 、 三氟甲磺酸三甲基硅酯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 38.33h， 生成 6-氯-9-(2,3,5-三苯甲酰氧基-2-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤
  参考文献：
  名称：

  [EN] CYCLIC DINUCLEOTIDES AS STING AGONISTS
  [FR] DINUCLÉOTIDES CYCLIQUES UTILISÉS EN TANT QU'AGONISTES DE STING

  摘要：

  本文披露了一种通过调节STING来治疗受影响的疾病、综合症或疾病的化合物、组合物和方法。这些化合物由以下公式（I）表示：其中R1A、R1B、R1C、R1D、B1、R2A、R2B、R2C、R2D和R2E在此定义，并且公式（II）中，其中R1H、R1K、R1J和R2L在此定义。

  公开号：

  WO2018138684A1

文献信息

• <i>N</i>⁶-Cycloalkyl- and <i>N</i>⁶-Bicycloalkyl-<i>C</i>5′(<i>C</i>2′)-modified Adenosine Derivatives as High-Affinity and Selective Agonists at the Human A₁ Adenosine Receptor with Antinociceptive Effects in Mice
  作者：Palmarisa Franchetti、Loredana Cappellacci、Patrizia Vita、Riccardo Petrelli、Antonio Lavecchia、Sonja Kachler、Karl-Norbert Klotz、Ida Marabese、Livio Luongo、Sabatino Maione、Mario Grifantini

  DOI：10.1021/jm801456g

  日期：2009.4.23

  N6-(endo-norborn-2-yl)adenosine derivatives, 5′-chloro-5′-deoxy-CPA (1) and 5′-chloro-5′-deoxy-(±)-ENBA (3) displayed the highest affinity in the subnanomolar range and relevant selectivity for hA1 vs the other human receptor subtypes. The higher affinity and selectivity of 5′-chloro-5′-deoxyribonucleoside derivatives 1 and 3 for hA1 AR vs hA3 AR compared to that of the parent 5′-hydroxy compounds CPA and (±)-ENBA

  为了进一步研究新型有效和选择性的人A 1腺苷受体激动剂，我们合成了一系列5'-氯-5'-脱氧-和5'-（2-氟苯硫基）-5'-脱氧-N 6-环烷基（双环烷基）-取代的腺苷和2'- C-甲基腺苷衍生物。评价这些化合物对人A 1，A 2A，A 2B和A 3腺苷受体的亲和力和功效。在一系列N 6-环戊基和N 6-（内降冰片-2-基）腺苷衍生物中，5'-chloro-5'-deoxy-CPA（1）和5'-chloro-5'- deoxy-CPA（1） （±）-ENBA（3）显示出在亚纳摩尔范围内的最高亲和力和对hA 1的选择性相对于其他人类受体亚型。5'-chloro-5'-脱氧核糖核苷衍生物1和3对hA 1 AR与hA 3 AR的亲和力和选择性与母体5'-羟基化合物CPA和（±）-ENBA的亲和力和选择性通过分子合理化建模分析。5'-Chloro-5'-deoxy-（±）-ENBA在福尔马林试验
• Antitumor Activity of <i>C</i>-Methyl-β-<scp>d</scp>-ribofuranosyladenine Nucleoside Ribonucleotide Reductase Inhibitors
  作者：Palmarisa Franchetti、Loredana Cappellacci、Michela Pasqualini、Riccardo Petrelli、Patrizia Vita、Hiremagalur N. Jayaram、Zsuzsanna Horvath、Thomas Szekeres、Mario Grifantini

  DOI：10.1021/jm048944c

  日期：2005.7.1

  A series of adenosine derivatives substituted at the 1'-, 2'-, or 3'-position of the ribose ring with a methyl group was synthesized and evaluated for antitumor activity. From this study 3'-C-methyladenosine (3'-Me-Ado) emerged as the most active compound, showing activity against human myelogenous leukemia K562, multidrug resistant human leukemia K562IU, human promyelocytic leukemia HL-60, human colon

  合成了一系列在核糖环的1'-，2'-或3'-位被甲基取代的腺苷衍生物，并评估了其抗肿瘤活性。通过这项研究，3'-C-甲基腺苷（3'-Me-Ado）作为最活跃的化合物出现，显示出对人骨髓性白血病K562，多药耐药性人白血病K562IU，人早幼粒细胞白血病HL-60，人结肠癌HT- 29和人类乳腺癌MCF-7细胞系，IC（50）值范围从11到38μM。结构-活性关系研究表明3'-Me-Ado的结构对于该活性至关重要。用小的烷基或环烷基取代N（6）-氨基的氢原子，在嘌呤环的2位引入氯原子，或甲基从3'位置移至其他核糖位置导致抗肿瘤活性降低或丧失。3'-Me-Ado的抗增殖活性似乎与其通过核糖核苷酸还原酶抑制作用同时耗尽细胞内嘌呤和嘧啶脱氧核苷酸的能力有关。
• Synthesis of purine modified 2′-C-methyl nucleosides as potential anti-HCV agents
  作者：Hong-wang Zhang、Longhu Zhou、Steven J. Coats、Tamara R. McBrayer、Phillip M. Tharnish、Lavanya Bondada、Mervi Detorio、Sarah A. Amichai、Melissa D. Johns、Tony Whitaker、Raymond F. Schinazi

  DOI：10.1016/j.bmcl.2011.09.034

  日期：2011.11

  Based on the anti-hepatitis C activity of 2′-C-methyl-adenosine and 2′-C-methyl-guanosine, a series of new modified purine 2′-C-methyl nucleosides was prepared as potential anti-hepatitis C virus agents. Herein, we report the synthesis of both 6-modified and 2-modified purine 2′-C-methyl-nucleosides along with their anti-HCV replication activity and cytotoxicity in different cells.

  基于2' - C-甲基-腺苷和2' - C-甲基-鸟苷的抗丙型肝炎活性，制备了一系列新型修饰嘌呤2'- C-甲基核苷作为潜在的抗丙型肝炎病毒药物. 在此，我们报告了 6-修饰和 2-修饰的嘌呤 2' - C-甲基-核苷的合成以及它们在不同细胞中的抗 HCV 复制活性和细胞毒性。
• Inhibitors of E1 activating enzymes
  申请人：Critchley Stephen

  公开号：US20060189636A1

  公开（公告）日：2006-08-24

  This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.

  本发明涉及抑制E1激活酶的化合物，包括该化合物的制药组合物和使用该化合物的方法。该化合物对于治疗疾病特别是细胞增殖性疾病，包括癌症，炎症和神经退行性疾病；以及与感染和消瘦相关的炎症具有用处。
• INHIBITORS OF E1 ACTIVATING ENZYMES
  申请人：Critchley Stephen

  公开号：US20110136834A1

  公开（公告）日：2011-06-09

  This invention relates to compounds that inhibit E1 activating enzymes, pharmaceutical compositions comprising the compounds, and methods of using the compounds. The compounds are useful for treating disorders, particularly cell proliferation disorders, including cancers, inflammatory and neurodegenerative disorders; and inflammation associated with infection and cachexia.

  本发明涉及抑制E1激活酶的化合物、包含该化合物的药物组合物以及使用该化合物的方法。该化合物可用于治疗疾病，特别是细胞增殖障碍，包括癌症、炎症和神经退行性疾病；以及与感染和消瘦相关的炎症。