9-(α-L-lyxofuranosyl)adenine | 16136-63-3

• 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: 9-(α-L-lyxofuranosyl)adenine
• 英文别名: AraAde；1-(6-amino-purin-9-yl)-α-L-1-deoxy-lyxofuranose；9-α-L-Lyxofuranosyl-adenin；(2S,3S,4R,5R)-2-(6-Amino-purin-9-yl)-5-hydroxymethyl-tetrahydro-furan-3,4-diol；(2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 16136-63-3
• 化学式: C₁₀H₁₃N₅O₄
• 分子量: 267.244
• InChiKey: OIRDTQYFTABQOQ-HGOUYRHRSA-N

物化性质

• 沸点：
  676.3±65.0 °C(Predicted)
• 密度：
  2.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  19
• 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

反应信息

• 作为反应物：
  描述：

  9-(α-L-lyxofuranosyl)adenine 在 盐酸 、 甲醇 、 偶氮二甲酸二异丙酯 、 三苯基膦 、 肼 作用下， 以 四氢呋喃 、 乙醇 、 丙酮 为溶剂， 反应 4.5h， 生成 9-(5-amino-5-deoxy-2,3-O-isopropylidene-α-L-lyxofuranosyl)adenine
  参考文献：
  名称：

  Adenosine Kinase Inhibitors. 3. Synthesis, SAR, and Antiinflammatory Activity of a Series of l-Lyxofuranosyl Nucleosides

  摘要：

  Chronic inflammatory diseases, such as arthritis and rheumatoid arthritis, remain major health problems worldwide. We previously demonstrated that adenosine kinase inhibitors (AKIs) exhibit antiinflammatory effects by inhibiting TNF-alpha production, neutrophil accumulation, and edema formation. Although adenosine receptor agonists produce similar effects, AKIs showed the antiinflammatory activity without the cardiovascular side effects that prevented the development of adenosine receptor specific agonists. However, previously described potent AKIs, such as 5-iodotubercidin, are nucleosides which have the potential to undergo in vivo 5'-O-phosphorylation and therefore produce cytotoxicity. In an effort to eliminate toxicities produced by phosphorylated nucleosides, L-lyxofuranosyl analogues of tubercidin were tested as potential AKIs since the opposite stereochemical. orientation of the CH2OH was expected to eliminate intracellular phosphorylation. Described herein are the discovery of a new series of AKIs based on alpha-L-lyxofuranosyl. nucleosides, their SAR, as well as the antiinflammatory activity of the lead compound GP790 (IC50 = 0.47 nM, 47% inhibition of paw swelling at 10 mg/kg in rat carrageenan paw edema model). In addition, a study showing that in the skin lesion model the antiinflammatory activity is reversed by an A2 selective adenosine receptor antagonist 3,7-dimethyl-1-propylxanthine (DMPX) is also described.

  DOI：

  10.1021/jm030230z
• 作为产物：
  描述：

  methyl L-lyxofuranoside 在 4-二甲氨基吡啶 、 硫酸 、 sodium methylate 、 四氯化锡 、 溶剂黄146 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 48.0h， 生成 9-(α-L-lyxofuranosyl)adenine
  参考文献：
  名称：

  Adenosine Kinase Inhibitors. 3. Synthesis, SAR, and Antiinflammatory Activity of a Series of l-Lyxofuranosyl Nucleosides

  摘要：

  Chronic inflammatory diseases, such as arthritis and rheumatoid arthritis, remain major health problems worldwide. We previously demonstrated that adenosine kinase inhibitors (AKIs) exhibit antiinflammatory effects by inhibiting TNF-alpha production, neutrophil accumulation, and edema formation. Although adenosine receptor agonists produce similar effects, AKIs showed the antiinflammatory activity without the cardiovascular side effects that prevented the development of adenosine receptor specific agonists. However, previously described potent AKIs, such as 5-iodotubercidin, are nucleosides which have the potential to undergo in vivo 5'-O-phosphorylation and therefore produce cytotoxicity. In an effort to eliminate toxicities produced by phosphorylated nucleosides, L-lyxofuranosyl analogues of tubercidin were tested as potential AKIs since the opposite stereochemical. orientation of the CH2OH was expected to eliminate intracellular phosphorylation. Described herein are the discovery of a new series of AKIs based on alpha-L-lyxofuranosyl. nucleosides, their SAR, as well as the antiinflammatory activity of the lead compound GP790 (IC50 = 0.47 nM, 47% inhibition of paw swelling at 10 mg/kg in rat carrageenan paw edema model). In addition, a study showing that in the skin lesion model the antiinflammatory activity is reversed by an A2 selective adenosine receptor antagonist 3,7-dimethyl-1-propylxanthine (DMPX) is also described.

  DOI：

  10.1021/jm030230z

文献信息

• Anticancer and Antiviral Effects and Inactivation of <i>S</i>-Adenosyl-<scp>l</scp>-homocysteine Hydrolase with 5‘-Carboxaldehydes and Oximes Synthesized from Adenosine and Sugar-Modified Analogues
  作者：Stanislaw F. Wnuk、Chong-Sheng Yuan、Ronald T. Borchardt、Jan Balzarini、Erik De Clercq、Morris J. Robins

  DOI：10.1021/jm960828p

  日期：1997.5.1

  5'-carboxaldehyde analogues by Moffatt oxidation (dimethyl sulfoxide/dicyclohexylcarbodiimide/dichloroacetic acid) or with the Dess-Martin periodinane reagent. Hydrolysis of a 5'-fluoro-5'-S-methyl-5'-thio (alpha-fluoro thioether) arabinosyl derivative also gave the 5'-carboxaldehyde. Treatment of 5'-carboxaldehydes with hydroxylamine [or O-(methyl, ethyl, and benzyl)hydroxylamine] hydrochloride gave

  通过Moffatt氧化（二甲基亚砜/二环己基碳二亚胺/二氯乙酸）或用Dess-Martin高碘烷试剂将选择性保护的腺嘌呤核苷转化为5'-甲醛醛类似物。5'-氟-5'-S-甲基-5'-硫代（α-氟硫醚）阿拉伯糖基衍生物的水解也得到5'-甲醛。用羟胺[或O-（甲基，乙基和苄基）羟胺]盐酸盐处理5'-甲醛，得到E / Z肟。用三氟乙酸水溶液和丙酮处理纯化的肟可实现反式肟化反应，从而提供干净的5'-甲醛样品。腺苷（Ado）-5'-甲醛及其4'-末端是S-腺苷-L-高半胱氨酸（AdoHcy）水解酶的有效抑制剂。它们与酶有效结合并在C3'处发生氧化 得到3'-酮类似物，同时降低NAD +辅因子，得到无活性的，紧密结合的NADH-酶复合物（I型辅因子耗竭抑制）。用含有核糖顺式2'，3'-乙二醇的5'-羧醛观察到了有效的I型抑制作用。它们的肟衍生物是“前抑制剂”，它们经过酶催化水解后在活性位点释放抑制剂。
• Mutant purine nucleoside phosphorylase proteins and cellular delivery thereof
  申请人：Ealick E. Steven

  公开号：US20050214901A1

  公开（公告）日：2005-09-29

  A host cell stably transformed or transfected by a vector including a DNA sequence encoding for mutant purine nucleoside cleavage enzymes is provided. The transformed or transfected host cell can be used in combination with a purine substrate to treat tumour cells and/or virally infected cells. A nucleotide sequence encoding mutant E. coli derived purine nucleoside phosphorylase proteins which can be used in conjunction with an appropriate substrate to produce toxins which impair abnormal cell growth is also provided. A method is detailed for the delivery of toxin by generation withing target cells or by administration and delivery to the cells from without. Novel purine nucleosides are detailed that yield a cytotoxic purine upn enzymatic cleavage. A synthetic process for nucleosides is also detailed.

  提供了一种由载有突变嘌呤核苷酸裂解酶编码DNA序列的载体转化或转染的宿主细胞。该转化或转染的宿主细胞可与嘌呤底物结合，用于治疗肿瘤细胞和/或病毒感染的细胞。还提供了编码突变E. coli来源的嘌呤核苷酰化酶蛋白的核苷酸序列，可与适当的底物结合使用，产生有害细胞生长的毒素。详细介绍了一种通过靶细胞内生成或通过外部给药和传递给细胞的毒素递送方法。详细介绍了产生细胞毒性嘌呤核苷酶裂解产物的新型嘌呤核苷。还详细介绍了一种核苷的合成过程。
• [EN] L-NUCLEOSIDE DIMER COMPOUNDS AND THERAPEUTIC USES<br/>[FR] COMPOSES DE DIMERES DE NUCLEOSIDES ET LEURS USAGES THERAPEUTIQUES
  申请人：LIPITEK INTERNATIONAL, INC.

  公开号：WO1997011087A1

  公开（公告）日：1997-03-27

  (EN) The invention relates to nucleoside dimers containing an L-sugar in at least one of the nucleosides and their pharmaceutical compositions.(FR) L'invention porte sur des dimères de nucléosides dont l'un au moins des nucléosides comporte un sucre L, ainsi que sur des préparations pharmaceutiques les contenant.

  该发明涉及含有至少一种L-糖在核苷中的核苷二聚体及其制药组合物。
• [EN] NOVEL NUCLEOSIDE ANALOGS AND USES IN TREATING DISEASE<br/>[FR] NOUVEAUX ANALOGUES DE NUCLEOSIDES ET LEURS UTILISATIONS DANS LE TRAITEMENT DE MALADIES
  申请人：LIPITEK INTERNATIONAL, INC.

  公开号：WO1999045935A1

  公开（公告）日：1999-09-16

  (EN) The invention relates to novel nucleosides and nucleoside dimers containing an L-sugar in at least one of the nucleosides, and their pharmaceutical compositions.(FR) L'invention concerne de nouveaux nucléosides, de nouveaux dimères de nucléosides dont l'un au moins des nucléosides comporte un sucre L, ainsi que des compositions pharmaceutiques les contenant.

  该发明涉及一种含有至少一个L-糖的新型核苷和核苷二聚体，以及它们的药物组合物。
• ADENOSINE KINASE INHIBITORS COMPRISING LYXOFURANOSYL DERIVATIVES
  申请人：GENSIA, INC.

  公开号：EP0684953A1

  公开（公告）日：1995-12-06