methyl 2,3-O-isopropylidene-L-lyxofuranoside | 84894-45-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2,3-O-isopropylidene-L-lyxofuranoside
• 英文别名: 1-O-methyl-2,3-O-isopropylidene-β-D-ribofuranose；Methyl-2,3-O-isopropyliden-α-L-lyxofuranosid；[(3aR,6S,6aR)-4-methoxy-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol
• CAS: 84894-45-1
• 化学式: C₉H₁₆O₅
• 分子量: 204.223
• InChiKey: DXBHDBLZPXQALN-FWYCZPIQSA-N

物化性质

• 沸点：
  287.3±40.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 2,3-O-isopropylidene-L-lyxofuranoside 在 盐酸 作用下， 以 甲醇 为溶剂， 以18 g的产率得到methyl L-lyxofuranoside
  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：

  甲基-2,3-O-异亚丙基-D-呋喃核糖苷 在 sodium periodate 、 lithium aluminium tetrahydride 、 ruthenium oxychloride 、 sodium methylate 作用下， 反应 10.0h， 生成 methyl 2,3-O-isopropylidene-L-lyxofuranoside
  参考文献：
  名称：

  Holy, Antonin, Collection of Czechoslovak Chemical Communications, 1982, vol. 47, # 11, p. 2969 - 2988

  摘要：

  DOI：

文献信息

• Inhibitors of E1 activating enzymes
  申请人：Langston P. Steven

  公开号：US20070191293A1

  公开（公告）日：2007-08-16

  This invention relates to compounds that inhibit E 1 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.

  该发明涉及抑制E1激活酶的化合物，包括这些化合物的药物组合物，以及使用这些化合物的方法。这些化合物可用于治疗疾病，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。
• INHIBITORS OF E1 ACTIVATING ENZYMES
  申请人：Langston Steven P.

  公开号：US20120258927A1

  公开（公告）日：2012-10-11

  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。该化合物可用于治疗疾病，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。
• INHIBITORS OF E1 ACTIVTING ENZYMES
  申请人：MILLENNIUM PHARMACEUTICALS, INC

  公开号：US20130289037A1

  公开（公告）日：2013-10-31

  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非常有用。
• Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists
  作者：Christelle Moreau、Tanja Kirchberger、Joanna M. Swarbrick、Stephen J. Bartlett、Ralf Fliegert、Timur Yorgan、Andreas Bauche、Angelika Harneit、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm401497a

  日期：2013.12.27

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.
• Design, Synthesis, and Antiviral Activity of α-Nucleosides:  <scp>d</scp>- and <scp>l</scp>-Isomers of Lyxofuranosyl- and (5-Deoxylyxofuranosyl)benzimidazoles
  作者：Michael T. Migawa、Jean-Luc Girardet、John A. Walker、George W. Koszalka、Stanley D. Chamberlain、John C. Drach、Leroy B. Townsend

  DOI：10.1021/jm970545c

  日期：1998.4.1

  Several 2-substituted alpha-D- and alpha-L-lyxofuranosyl and 5-deoxylyxofuranosyl derivatives of 5,6-dichloro-2-(isopropylamino)-1- -(beta-L-ribofuranosyl)benzimidazole (1263W94) and 2,5,6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) were synthesized and evaluated for activity against two herpesviruses (HSV-1 and HCMV) and for their cytotoxicity against HFF and KB cells. Condensation of 1,2,3,5-tetra-O-acetyl-L-lyxofuranose (2a) with 2,5,6-trichlorobenzimidazole (1) yielded the or-nucleoside 3a. The 2-bromo derivative and 2-methylamino derivative were prepared by treatment of 3a with HBr followed by deprotection or from methylamine, respectively. Compound 3a was deprotected and the resultant nucleoside used to prepare the 2-cyclopropylamino and 2-isopropylamino derivatives. The 2-alkylthio nucleosides were prepared by condensing 2a with 5,6-dichlorobenzimidazole-2-thione followed by deprotection. Alkylation of this adduct gave the 2-methylthio and 2-benzylthio derivatives. Condensation of 5-deoxy-1,2,3-tri-O-acetyl-L-lyxofuranosyl, prepared from L-lyxose, with 1 or 2-bromo-5,6-dichlorobenzimidazole (15), followed by deprotection, gave the 2-chloro or 2-bromo-5'-deoxylyxofuranosyl derivative, respectively. The cyclopropylamino derivative was prepared from the 2-chloro derivative. All D-isomers were prepared in an analogous fashion from D-lyxose. Either compounds were inactive against HSV-1 or weak activity was poorly separated from cytoxicity. In contrast, the 2-halogen derivatives in both the alpha-lyxose and 5-deoxy-alpha-lyxose series were active against the Towne strain of HCMV. The 5-deoxy alpha-L analogues were the most active, IC50's = 0.2-0.4 mu M, plaque assay; IC90's = 0.2-2 mu M, yield reduction assay. All of the 2-isopropylamino or 2-cyclopropylamino derivatives were less active (IC50's = 60-100 mu M, plaque assay; IC90's = 17-100 mu M, yield reduction assay) and were not cytotoxic. The methylamino, thio, and methylthio derivatives were neither active nor cytotoxic. The benzylthio derivatives were weakly active, but this activity was poorly separated from cytotoxicity. The alpha-lyxose L-isomers were more active in a plaque assay against the AD169 strain of HCMV compared to the Towne strain, thereby providing additional evidence of antiviral specificity.