8-氯腺嘌呤核苷 | 34408-14-5

• 物质功能分类: 生物化工 - 核苷类药物 - 核苷中间体
• 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: 8-氯腺嘌呤核苷
• 中文别名: 8-氯腺苷酸
• 英文名称: 8-chloroadenosine
• 英文别名: 8-chloro-adenosine；8‑chloroadenosine；8-chloropurine riboside；8-Cl-Ado；(2R,3R,4S,5R)-2-(6-amino-8-chloropurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 34408-14-5
• 化学式: C₁₀H₁₂ClN₅O₄
• 分子量: 301.689
• InChiKey: MHDPPLULTMGBSI-UUOKFMHZSA-N

物化性质

• 熔点：
  189-191 °C
• 沸点：
  707.4±70.0 °C(Predicted)
• 密度：
  2.19±0.1 g/cm3(Predicted)
• 溶解度：
  温和加热下在水中溶解度为 20 mM，在 DMSO 中溶解度为 100 mM

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 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：
  140
• 氢给体数：
  4
• 氢受体数：
  8

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  8-氯腺嘌呤核苷 在 吡啶 、 亚硝酸特丁酯 、 碳酸氢铵 作用下， 以 四氢呋喃 为溶剂， 反应 141.0h， 生成 8-Chloro-purine riboside
  参考文献：
  名称：

  Synthesis and Biologic Evaluation of 8-Substituted Derivatives of Nebularine (9-β-D-Ribofuranosylpurine)

  摘要：

  A series of 8-substituted purine ribonucleosides were prepared from 2',3',5'-tri-O-acetyl-8-bromoadenosine and evaluated for cytotoxicity and antiviral activity. Four of these nucleosides (6b-9b) were significantly toxic to both HEp-2 and L1210 cells in culture but the most cytotoxic one (9b) was inactive against the P388 leukemia in mice. None of these nucleosides showed significant antiviral activity against Herpes Simplex 1 or 2, vaccinia, or influenza A.

  DOI：

  10.1080/15257779408011875
• 作为产物：
  描述：

  8-mercaptoadenosine 在 N-氯代丁二酰亚胺 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以52%的产率得到8-氯腺嘌呤核苷
  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

• [EN] PAPD5 INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE PAPD5 ET LEURS PROCÉDÉS D'UTILISATION
  申请人：CHILDRENS MEDICAL CENTER

  公开号：WO2020219729A1

  公开（公告）日：2020-10-29

  The present application provides compounds that are PAPD5 inhibitors and are useful in treating a variety of conditions such as cancer, telomere diseases, and aging-related and other degenerative disorders.

  本申请提供了一些PAPD5抑制剂化合物，可用于治疗各种疾病，如癌症、端粒疾病以及与衰老和其他退行性疾病相关的情况。
• [EN] SYNTHESIS OF 8-CHLOROADENOSINE DERIVATIVES INCLUDING NUC-9701<br/>[FR] SYNTHÈSE DE DÉRIVÉS DE 8-CHLOROADÉNOSINE COMPRENANT NUC-9701
  申请人：NUCANA PLC

  公开号：WO2020128469A1

  公开（公告）日：2020-06-25

  The present invention generally relates to a novel process for the preparation of 8-chloroadenosine derivatives, and particularly NUC-9701(8-chloroadenosine-5'-O- [naphthyl(benzyloxy-L-alaninyl)] phosphate) an anticancer ProTide of 8-chloroadenosine.

  本发明通常涉及一种新型制备8-氯腺苷衍生物的过程，特别是NUC-9701（8-氯腺苷-5'-O-[萘基(苄氧基-L-丙氨酰)]磷酸酯），一种8-氯腺苷的抗癌ProTide。
• Symmetrical Diamidates as a Class of Phosphate Prodrugs to Deliver the 5′‐Monophosphate Forms of Anticancer Nucleoside Analogues
  作者：Magdalena Slusarczyk、Valentina Ferrari、Michaela Serpi、Blanka Gönczy、Jan Balzarini、Christopher McGuigan

  DOI：10.1002/cmdc.201800504

  日期：2018.11.6

  The application of phosphorodiamidate technology to pyrimidine and purine nucleosides with anticancer activity to potentially overcome the resistance mechanisms associated with parent nucleosides is reported. Sixteen symmetrical phosphorodiamidates were prepared from the natural amino acids l‐alanine and glycine. All the compounds were evaluated for their cytotoxic activity against a wide panel of

  报道了将二氨基磷酸酯技术应用于具有抗癌活性的嘧啶和嘌呤核苷，以潜在地克服与亲本核苷相关的抗性机制。由天然氨基酸l-丙氨酸和甘氨酸制备了16种对称的二氨基氨基磷酸酯。评估了所有化合物对多种实体和白血病肿瘤细胞系的细胞毒活性。此外，对代表性的二氨基磷酸二酰胺酯进行了羧肽酶Y分析，以揭示所报道的二氨基磷酸酯类前药的假定生物活化途径。
• 6,8-DISUBSTITUTED PURINE COMPOSITIONS
  申请人：ZAHAJSKA Lenka

  公开号：US20130072506A1

  公开（公告）日：2013-03-21

  6,8-Disubstituted purines which can be used in drug and cosmetic compositions and/or applications are provided. These 6,8-disubstituted purines have a wide range of biological activities, including for example anti-inflammatory, anti-senescent, as well as well as other activities which are especially useful in pharmaceutical and cosmetic applications. The 6,8-disubstituted purine compounds and compositions containing such 6,8-disubstituted purines provide growth-regulatory, differentiating, antisenescent and antiaging properties with improved selectivities and efficiencies and lower toxicities than analogues known heretofore.

  提供可用于药物和化妆品组合物和/或应用的6,8-二取代嘌呤。这些6,8-二取代嘌呤具有广泛的生物活性，例如抗炎、抗衰老等，以及其他在制药和化妆品应用中特别有用的活性。含有这些6,8-二取代嘌呤的化合物和组合物提供生长调节、分化、抗衰老和抗衰老特性，具有比迄今为止已知的类似物更好的选择性和效率，以及较低的毒性。
• [EN] ADENOSINE DERIVATIVES FOR USE IN THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS DE L'ADÉNOSINE UTILISABLES DANS LE TRAITEMENT DU CANCER
  申请人：NUCANA BIOMED LTD

  公开号：WO2017207989A1

  公开（公告）日：2017-12-07

  The present invention relates to chemical compounds of formula (I) as defined in the amended claims, their preparation and their use in the treatment of cancer.

  本发明涉及化学式（I）所定义的化合物，其制备以及在癌症治疗中的应用。