N1-Oxy-N6-methyl-adenosine | 113509-54-9

• 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: N1-Oxy-N6-methyl-adenosine
• 英文别名: N⁶-methyladenosine N¹-oxide
• CAS: 113509-54-9
• 化学式: C₁₁H₁₅N₅O₅
• 分子量: 297.271
• InChiKey: VPJWDUHOSAHXFE-IOSLPCCCSA-N

物化性质

• 沸点：
  740.5±70.0 °C(Predicted)
• 密度：
  1.92±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.28
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  139.6
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  N1-Oxy-N6-methyl-adenosine 在 sodium hydroxide 作用下， 反应 8.0h， 生成 N⁶-methyl-2-(5-hexenylthio)adenosine
  参考文献：
  名称：

  Identification of potent, selective P2Y-purinoceptor agonists: structure-activity relationships for 2-thioether derivatives of adenosine 5'-triphosphate

  摘要：

  Study of P-2-purinoceptor subtypes has been difficult due to the lack of potent and selective ligands. With the goal of developing high affinity P-2-purinoceptor-selective agonists, we have synthesized a series of analogues of adenine nucleotides modified on the purine ring as chain-extended 2-thioethers or as N-6-methyl-substituted compounds. Chemical functionality incorporated in the thioether moiety included cyanoalkyl, nitroaromatic, amino, thiol, cycloalkyl, n-alkyl, and olefinic groups. Apparent affinity of the compounds for P-2Y-purinoceptors was established by measurement of P-2Y-purinoceptor-promoted phospholipase C activity in turkey erythrocyte membranes and relaxation of carbachol-contracted smooth muscle in three different preparations (guinea pig taenia coli, rabbit aorta, and rabbit mesenteric artery). Activity at P-2X-purinoceptors was established by measurement of contraction of rabbit saphenous artery and of the guinea pig vas deferens and urinary bladder. All 11 of the 2-thioethers of ATP stimulated the production of inositol phosphates with K-0.5 values of 1.5-770 nM, with an (aminophenyl)ethyl derivative being most potent. Two adenosine diphosphate analogues were equipotent to the corresponding ATP analogues. Adenosine monophosphate analogues were full agonists, although generally 4 orders of magnitude less potent. ATP 2-thioethers displayed pD(2) values in the range of 6-8 in smooth muscle assay systems for activity at P-2Y-receptors. There was a significant correlation for the 2-thioether compounds between the pK(0.5) values for inositol phosphate production and the pD(2) values for relaxation mediated via the P-2Y-purinoceptors in the guinea pig taenia coli, but not for the vascular P-2Y-receptors or for the P-2X-receptors. At P-2X-receptors, no activity was observed in the rabbit saphenous artery, but variable degrees of activity were observed in the guinea pig vas deferens and bladder depending on distal substituents of the thioether moiety. N-6-Methyl-ATP was inactive at P-2X-receptors, and approximately equipotent to ATP at taenia coli P-2Y-receptors. This suggested that hybrid N-6-methyl and 2-thioether ATP derivatives might be potent and selective for certain P-2Y-receptors, as was shown for one such derivative, N-6-methyl-2-(5-hexenylthio)-ATP.

  DOI：

  10.1021/jm00076a023
• 作为产物：
  描述：

  N⁶-methyladenosine 在 间氯过氧苯甲酸 作用下， 以 甲醇 为溶剂， 反应 42.0h， 以53%的产率得到N1-Oxy-N6-methyl-adenosine
  参考文献：
  名称：

  Adenosine N1-Oxide Analogues as Inhibitors of Orthopox Virus Replication

  摘要：

  几种新型腺苷N1-氧化物（ANO）衍生物，包括N1-烷氧基和N6-烷基，以及在核糖核苷残基位置具有三羟基环戊烷环的类似物已合成，并在感染了痘疹病毒、小鼠痘病毒、猴痘病毒、牛痘病毒和不同种类天花病毒的Vero和LLC-MK2细胞培养物中评估了它们的抗病毒性能。ANO及其衍生物的抗病毒活性显著取决于病毒类型和细胞培养物。小鼠痘病毒和猴痘病毒对这些化合物最为敏感，而痘疹病毒和牛痘病毒在浓度高1-1.5个数量级时被抑制。合成化合物的毒性远低于ANO。对ANO N6-位置的修饰并未比原始化合物提供任何优势。合成的诺阿利斯特罗霉素N1-氧化物衍生物保留了与诺阿利斯特罗霉素相当的活性，并显示出降低的毒性。未发现抗病毒活性与化合物稳定性之间的直接相关性。

  DOI：

  10.1135/cccc20061107

文献信息

• Biologically active ATP analogs
  申请人：The United States of America as represented by the Department of Health

  公开号：US05620676A1

  公开（公告）日：1997-04-15

  The present invention provides certain novel adenosine triphosphate (ATP) analogs, pharmaceutical compositions, and methods of using such analogs in the treatment of septic shock and other disease conditions. Examples of the ATP analogs include the mono-, di- and triphosphates of adenosines with various selected substituents at the 2, 6, 8, and 9-positions, such as alkyl, alkylphenyl, phenylalkyl, S-alkyl, S-alkenyl, S-alkylcyano, S-phenyl, S-alkylphenyl, S-alkylamino, S-alkylthioalkyl, S-alkylthiocyanato, S-alkylaminophenyl, S-alkylnitrophenyl, hydroxy, bromo, fluoro, chloro, and aminoalkylamino. The present invention also provides pharmaceutical compositions of and methods of using certain xanthine and uracil derivatives for the above disease conditions. Examples of the xanthine derivatives include xanthines having alkyl or alkyltriphosphate substituents at the 1, 3, and 7-positions. Examples of the uracil derivatives include 5-fluoro- and 5-bromo uracil triphosphates. Also provided are assays for assessing the binding of the ATP analogs.

  本发明提供了某些新型腺苷三磷酸（ATP）类似物、药物组合物以及使用这些类似物治疗败血性休克和其他疾病的方法。ATP类似物的示例包括在2、6、8和9位选择性取代基的腺苷单磷酸、腺苷二磷酸和腺苷三磷酸，例如烷基、烷基苯、苯基烷基、S-烷基、S-烯基、S-烷基氰、S-苯基、S-烷基苯基、S-烷基氨基、S-烷基硫代烷基、S-烷基硫氰酸、S-烷基氨基苯基、S-烷基硝基苯基、羟基、溴、氟、氯和氨基烷基氨基。本发明还提供了某些黄嘌呤和尿嘧啶衍生物的药物组合物和治疗上述疾病的方法。黄嘌呤衍生物的示例包括在1、3和7位具有烷基或烷基三磷酸取代基的黄嘌呤。尿嘧啶衍生物的示例包括5-氟和5-溴尿嘧啶三磷酸。还提供了评估ATP类似物结合的测定方法。
• Synthesis and Antiviral Evaluation of Analogs of Adenosine-<i>N</i>¹-Oxide and 1-(Benzyloxy)Adenosine
  作者：Cecil D. Kwong、Charles A. Krauth、Anita T. Shortnacy-Fowler、Gussie Arnett、Melinda G. Hollingshead、William M. Shannon、John A. Montgomery、John A. Secrist

  DOI：10.1080/07328319808003478

  日期：1998.8

  The application of recombinant DNA technology to vaccinia virus for the purpose of developing vaccines dates back nearly twenty years. Since that time a number of recombinant vaccinia-based vaccines have been developed for both veterinary(1-16) and human(17-27) use. Recent recombinant vaccinia vaccines for human use have focused on both cancer(18,19,21-24) and AIDS.(25-27) Several. reviews that summarize recent progress with poxvirus-based vaccines are available.(28-33) Over the years various anecdotal complications with vaccinia virus inoculations have been reported,(34-36) and other human safety concerns include potentially serious adverse consequences in immunocompromised individuals, and adverse reactions in a few normal individuals.(28) Other safety concerns relative to genetic changes in the virus also exist.(32) In view of these issues, some years ago the U.S. Army embarked on a program searching for small molecule drugs that could be used for the prevention or treatment of complications associated with the administration of either vaccinia virus itself or a recombinant vector derived from it. This report presents data on a series of compounds that we prepared as a part of that program.(37).
• Oxidative transformations of minor components of nucleic acids. An anomalous reaction course of oxidation of N6,N6-dialkyladenosines and related compounds with m-chloroperoxybenzoic acid
  作者：Takeshi Endo、Jiri Zemlicka

  DOI：10.1021/jo00244a010

  日期：1988.4