3'-C-Methyladenosine | 15397-13-4

• 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: 3'-C-Methyladenosine
• 英文别名: 3'-Me-Ado；(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)-3-methyloxolane-3,4-diol
• CAS: 15397-13-4
• 化学式: C₁₁H₁₅N₅O₄
• 分子量: 281.271
• InChiKey: MLIWWOXSMXQECL-ZGUVBZSNSA-N

物化性质

• 沸点：
  643.4±65.0 °C(Predicted)
• 密度：
  1.89±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：
  0.55
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3'-C-Methyladenosine 在 氯化亚砜 、 2,2,6,6-四甲基哌啶氧化物 、 碘苯二乙酸 、 camphor-10-sulfonic acid 、 水 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 21.0h， 生成 ethyl 1-deoxy-1-(6-amino-9H-purin-9-yl)-3-C-methyl-2,3-O-isopropylidene-β-D-ribofuranuroate
  参考文献：
  名称：

  Synthesis, Biological Evaluation, and Molecular Modeling of Ribose-Modified Adenosine Analogues as Adenosine Receptor Agonists

  摘要：

  A number of 3'-C-methyl analogues of selective adenosine receptor agonists such as CPA, CHA, CCPA, 2'-Me-CCPA, NECA, and IB-MECA was synthesized to further investigate the subdomain of the receptor that binds the ribose moiety of the ligands. Affinity data at A(1), A(2A), and A(3) receptors in bovine brain membranes showed that the X-C-modification in adenosine resulted in a decrease of the affinity at all three receptor subtypes. When this modification was combined with N-6-substitution with groups that induce high potency and selectivity at A(1) receptor, the affinity and selectivity were increased. However, all X-C-methyl derivatives proved to be very less active than the corresponding 2'-C-methyl analogues. The most active compound was found to be 3'-Me-CPA which displayed a K-i value of 0.35 muM at A(1) receptor and a selectivity for A(1) vs A(2A) and A(3) receptors higher than 28-fold. 2'-Me-CCPA was confirmed to be the most selective, high affinity agonist so far known also at human A(1) receptor with a K-i value of 3.3 nM and 2903- and 341-fold selective vs human A(2A) and A(3) receptors, respectively. In functional assay, 3'-Me-CPA, 3'-Me-CCPA, and 2-Cl-3'-Me-IB-MECA inhibited forskolin-stimulated adenylyl cyclase activity with IC50 values ranging from 0.3 to 4.9 muM, acting as full agonists. A rhodopsin-based model of the bovine A(1)AR was built to rationalize the higher affinity and selectivity of 2'-C-methyl derivatives of N-6-substituted-adenosine compared to that of 3'-C-methyl analogues. In the docking exploration, it was found that 2'-Me-CCPA was able to form a number of interactions with several polar residues in the transmembrane helices TM-3, TM-6, and TM-7 of bA(1)AR which were not preserved in the molecular dynamics simulation of 3'-Me-CCPA/bA(1)AR complex.

  DOI：

  10.1021/jm049408n
• 作为产物：
  描述：

  6-氯嘌呤 在 palladium on activated charcoal 三氟甲磺酸三甲基硅酯 、 氨 、 ammonium formate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 1,4-二氧六环 、 甲醇 、 乙腈 为溶剂， 反应 29.0h， 生成 3'-C-Methyladenosine
  参考文献：
  名称：

  嘌呤核糖核苷抑制丙型肝炎病毒 RNA 依赖性 RNA 聚合酶的构效关系。

  摘要：

  作为识别丙型肝炎病毒 (HCV) 复制抑制剂的持续努力的一部分，我们在此报告了一系列核苷类似物及其相应的三磷酸盐的合成和评估。评估了核苷在基于细胞的亚基因组复制子系统中抑制 HCV RNA 复制的能力，而评估了核苷三磷酸抑制由 HCV RNA 依赖性 RNA 聚合酶 NS5B 介导的体外 RNA 合成的能力。2'-C-甲基腺苷和 2'-C-甲基鸟苷被确定为 HCV RNA 复制的有效抑制剂，并且发现相应的三磷酸盐是 HCV NS5B 介导的 RNA 合成的有效抑制剂。在基于细胞的测定中产生的数据证明了围绕活性核苷的相当严格的构效关系。发现 C2 上超过甲基的空间体积增加、甲基取代基的立体化学或区域化学的变化，或杂碱的特性变化超过内源性腺嘌呤或鸟嘌呤的变化，会导致抑制活性的丧失。结果突出了核糖构型 2'-和 3'-羟基药效团在基于细胞的测定中抑制 HCV RNA 复制的重要性，并证明包含 2

  DOI：

  10.1021/jm030424e

文献信息

• 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。
• 2-5A ANALOGS AND THEIR METHODS OF USE
  申请人：Beigelman Leonid

  公开号：US20100331397A1

  公开（公告）日：2010-12-30

  Disclosed herein are compounds that activate RNaseL, methods of synthesizing compounds that activate RNaseL and the use of compounds that activate RNaseL for treating and/or ameliorating a disease or a condition, such as a viral infection, a bacterial infection, cancer and/or parasitic disease.

  本文披露了激活RNaseL的化合物，合成激活RNaseL的化合物的方法，以及利用激活RNaseL的化合物治疗和/或改善疾病或状况的用途，例如病毒感染、细菌感染、癌症和/或寄生虫病。
• Synthesis, conformational analysis, and biological activity of new analogues of thiazole-4-carboxamide adenine dinucleotide (TAD) as IMP dehydrogenase inhibitors
  作者：Palmarisa Franchetti、Loredana Cappellacci、Michela Pasqualini、Riccardo Petrelli、Vetrichelvan Jayaprakasan、Hiremagalur N. Jayaram、Donald B. Boyd、Manojkumar D. Jain、Mario Grifantini

  DOI：10.1016/j.bmc.2005.01.007

  日期：2005.3

  T-3'-MeAD (2) containing, respectively, a methyl group at the ribose 2'-C-, and 3'-C-position of the adenosine moiety, were prepared as potential selective human inosine monophosphate dehydrogenase (IMPDH) type II inhibitors. The synthesis of heterodinucleotides was carried out by CDI-catalyzed coupling reaction of unprotected 2'-C-methyl- or 3'-C-methyl-adenosine 5'-monophosphate with 2',3'-O-isopr

  噻唑-4-羧酰胺腺嘌呤二核苷酸（TAD）类似物T-2'-MeAD（1）和T-3'-MeAD（2）分别在核糖2'-C-和3'-处含有甲基制备腺苷部分的C位作为潜在的选择性人肌苷单磷酸脱氢酶（IMPDH）II型抑制剂。杂二核苷酸的合成是通过CDI催化未保护的2'-C-甲基-或3'-C-甲基-腺苷5'-单磷酸酯与2'，3'-O-异亚丙基-噻唑啉5'-的偶联反应进行的一磷酸，然后脱异丙基。作为重组人IMPDH和I型II抑制剂的二核苷酸1和2的生物学评估导致了良好的活性。相对于NAD底物，T-2'-MeAD和T-3'-MeAD对同工酶的抑制是非竞争性的。T-3'的结合 -MeAD与母体化合物TAD相当，而T-2'-MeAD被证明是较弱的抑制剂。然而，在抑制IMPDH同工酶方面未发现显着差异。发现T-2'-MeAD和T-3'-MeAD抑制K562细胞的生长（IC（50）分别为30.7和65.0μM）。
• Synthesis, Biological, and Computational Evaluations of Conformationally Restricted NAD-Mimics as Discriminant Inhibitors of Human NMN-Adenylyltransferase Isozymes
  作者：Federica Matteucci、Marta Ferrati、Eleonora Spinozzi、Alessia Piergentili、Fabio Del Bello、Gianfabio Giorgioni、Leonardo Sorci、Riccardo Petrelli、Loredana Cappellacci

  DOI：10.3390/ph17060739

  日期：——

  Nicotinamide adenine dinucleotide (NAD) cofactor metabolism plays a significant role in cancer development. Tumor cells have an increased demand for NAD and ATP to support rapid growth and proliferation. Limiting the amount of available NAD by targeting critical NAD biosynthesis enzymes has emerged as a promising anticancer therapeutic approach. In mammals, the enzyme nicotinamide/nicotinic acid adenylyltransferase

  烟酰胺腺嘌呤二核苷酸 (NAD) 辅因子代谢在癌症发展中发挥着重要作用。肿瘤细胞对 NAD 和 ATP 的需求增加，以支持快速生长和增殖。通过靶向关键的 NAD 生物合成酶来限制可用 NAD 的量已成为一种有前景的抗癌治疗方法。在哺乳动物中，烟酰胺/烟酸腺苷酸转移酶 (NMNAT) 催化所有已知 NAD 合成途径的关键下游反应。合成了新型烟酰胺/烟酸腺嘌呤二核苷酸 (NAD/NaAD) 类似物 1-4，在腺苷部分的核糖 2'-C 和 3'-C-位置含有甲基，作为人类三种亚型的抑制剂NMN-腺苷酰转移酶，命名为 hNMNAT-1、hNMNAT-2 和 hNMNAT-3。基于 NMR 的构象分析表明，各个 NAD 类似物 (1-4) 具有不同的构象偏好。对二核苷酸 1-4 作为 hNMNAT 同工型抑制剂的生物学评估揭示了不同构象（北抗和南顺）与酶抑制活性之间的结构关系。在合成和测试的新系列 NAD
• METHODS AND COMPOSITIONS FOR TREATING HEPATITIS C VIRUS
  申请人：Idenix Pharmaceuticals LLC

  公开号：EP1292603B8

  公开（公告）日：2017-05-03