2',3',5'-tri-O-acetyl-8-bromo-2-iodoadenosine | 457061-00-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2',3',5'-tri-O-acetyl-8-bromo-2-iodoadenosine
• 英文别名: 2',3',5'-tri-O-Acetyl-2-iodo-8-bromoadenosine；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(6-amino-8-bromo-2-iodopurin-9-yl)oxolan-2-yl]methyl acetate
• CAS: 457061-00-6
• 化学式: C₁₆H₁₇BrIN₅O₇
• 分子量: 598.149
• InChiKey: RHFOQSKWYPJKJP-IDTAVKCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  158
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2',3',5'-tri-O-acetyl-8-bromo-2-iodoadenosine 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.0h， 生成 2-[(E)-1-hexenyl]-8-(methylamino)adenosine
  参考文献：
  名称：

  2,8-Disubstituted adenosine derivatives as partial agonists for the adenosine A2A receptor

  摘要：

  Novel 2,8-disubstituted adenosine derivatives were synthesized in good overall yields starting from 2-iodoadenosine. Binding affinities were determined for rat adenosine A(1) and A(2A) receptors and human A(3) receptors. Some compounds displayed good adenosine A(2A) receptor affinities, with most of the 2-(I-hexynyl)- and 2-[(E)-1-hexenyl]-substituted derivatives having K-i values in the nanomolar range. Although the introduction of an 8-alkylamino substituents decreased the affinity for the adenosine A(2A) receptor somewhat, the selectivity for this receptor compared to A(3) was improved significantly. The 8-methylamino (12) and 8-propylamino (14) derivatives of 2-(1-hexynyl)adeno sine (3), showed reasonable A(2A) receptor affinities with Ki values of 115 and 82 nM, respectively, and were 49- and 26-fold selective for the adenosine A(2A) receptor compared to the A(3) receptor. The compounds were also evaluated for their ability to stimulate the cAMP production in CHO cells expressing the human adenosine A(2A) receptor. 2-(I-Hexynyl)adenosine (3) and 2-[(E)-1-hexenyl]adenosine (4) both showed submaximal levels of produced cAMP, compared to the reference full agonist CGS 21680, and thus behaved as partial agonists. Most 8-alkylamino-substituted derivatives of 3, displayed similar cAMP production as 3, and behaved as partial agonists as well. Introduction of alkylamino groups at the 8-position of 4, showed a slight reduction of the efficacy compared to 4, and these compounds were partial agonists also. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00123-8
• 作为产物：
  描述：

  2-碘腺苷 在 4-二甲氨基吡啶 、 disodium hydrogenphosphate 、 溴 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 反应 1.0h， 生成 2',3',5'-tri-O-acetyl-8-bromo-2-iodoadenosine
  参考文献：
  名称：

  2,8-Disubstituted adenosine derivatives as partial agonists for the adenosine A2A receptor

  摘要：

  Novel 2,8-disubstituted adenosine derivatives were synthesized in good overall yields starting from 2-iodoadenosine. Binding affinities were determined for rat adenosine A(1) and A(2A) receptors and human A(3) receptors. Some compounds displayed good adenosine A(2A) receptor affinities, with most of the 2-(I-hexynyl)- and 2-[(E)-1-hexenyl]-substituted derivatives having K-i values in the nanomolar range. Although the introduction of an 8-alkylamino substituents decreased the affinity for the adenosine A(2A) receptor somewhat, the selectivity for this receptor compared to A(3) was improved significantly. The 8-methylamino (12) and 8-propylamino (14) derivatives of 2-(1-hexynyl)adeno sine (3), showed reasonable A(2A) receptor affinities with Ki values of 115 and 82 nM, respectively, and were 49- and 26-fold selective for the adenosine A(2A) receptor compared to the A(3) receptor. The compounds were also evaluated for their ability to stimulate the cAMP production in CHO cells expressing the human adenosine A(2A) receptor. 2-(I-Hexynyl)adenosine (3) and 2-[(E)-1-hexenyl]adenosine (4) both showed submaximal levels of produced cAMP, compared to the reference full agonist CGS 21680, and thus behaved as partial agonists. Most 8-alkylamino-substituted derivatives of 3, displayed similar cAMP production as 3, and behaved as partial agonists as well. Introduction of alkylamino groups at the 8-position of 4, showed a slight reduction of the efficacy compared to 4, and these compounds were partial agonists also. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00123-8

文献信息

• C2, 8-disubstituted adenosine derivatives and their different uses
  申请人：——

  公开号：US20040116374A1

  公开（公告）日：2004-06-17

  Novel C2, 8-disubstituted adenosine derivatives disclosed herein have been found to be potent adenosine receptor agonists, in particular for the A2A receptor. The said compounds have biological activity against conditions such as hypertension, ischemic heart disease, ischemic brain disease, psychosis and wound healing. Further, the invention also discloses a process for the preparation of such compounds and pharmaceutical compositions comprising them.

  本发明公开了 Novel C2，8-二取代腺苷衍生物，发现其是有效的腺苷受体激动剂，特别是对于A2A受体。所述化合物对高血压、缺血性心脏病、缺血性脑病、精神病和伤口愈合等疾病具有生物活性。此外，本发明还公开了制备这些化合物的方法和包含它们的药物组合物。
• C2,8-disubstituted adenosine derivatives and their different uses
  申请人：Universiteit Leiden

  公开号：US07112574B2

  公开（公告）日：2006-09-26

  Novel C2,8-disubstituted adenosine derivatives disclosed herein have been found to be potent adenosine receptor agonists, in particular for the A2A receptor. The said compounds have biological activity against conditions such as hypertension, ischemic heart disease, ischemic brain disease, psychosis and wound healing. Further, the invention also discloses a process for the preparation of such compounds and pharmaceutical compositions comprising them.

  本发明披露的新型C2,8-二取代腺苷衍生物被发现是有效的腺苷受体激动剂，特别是对于A2A受体。该化合物对高血压、缺血性心脏病、缺血性脑病、精神病和伤口愈合等疾病具有生物活性。此外，本发明还披露了一种制备这种化合物的方法和包含它们的制药组合物。
• RlmN and Cfr are Radical SAM Enzymes Involved in Methylation of Ribosomal RNA
  作者：Feng Yan、Jacqueline M. LaMarre、Rene Röhrich、Jochen Wiesner、Hassan Jomaa、Alexander S. Mankin、Danica Galonić Fujimori

  DOI：10.1021/ja910850y

  日期：2010.3.24

  Posttranscriptional modifications of ribosomal RNA (rRNA) nucleotides are a common mechanism of modulating the ribosome's function and conferring bacterial resistance to ribosome-targeting antibiotics. One such modification is methylation of an adenosine nucleotide within the peptidyl transferase center of the ribosome mediated by the endogenous methyltransferase RImN and its evolutionarily related resistance enzyme Cfr. These methyltransferases catalyze methyl transfer to aromatic carbon atoms of the adenosine within a complex 23S rRNA substrate to form the 2,8-dimethylated product. RImN and Cfr are members of the Radical SAM superfamily and contain the characteristic cysteine-rich CX3CX2C motif. We demonstrate that both enzymes are capable of accommodating the requisite [4Fe-4S] cluster. S-Adenosylmethionine (SAM) is both the methyl donor and the source of a 5'-deoxyadenosyl radical, which activates the substrate for methylation. Detailed analyses of the rRNA requirements show that the enzymes can utilize protein-free 23S rRNA as a substrate, but not the fully assembled large ribosomal subunit, suggesting that the methylations take place during the assembly of the ribosome. The key recognition elements in the 23S rRNA are helices 90-92 and the adjacent single stranded RNA that encompasses A2503. To our knowledge, this study represents the first in vitro description of a methyl transfer catalyzed by a member of the Radical SAM superfamily, and it expands the catalytic repertoire of this diverse enzyme class. Furthermore, by providing information on both the timing of methylation and its substrate requirements, our findings have important implications for the functional consequences of Cfr-mediated modification of rRNA in the acquisition of antibiotic resistance.
• C2, 8-DISUBSTITUTED ADENOSINE DERIVATIVES AND THEIR DIFFERENT USES
  申请人：Universiteit Leiden

  公开号：EP1368364B1

  公开（公告）日：2006-09-20
• US7112574B2
  申请人：——

  公开号：US7112574B2

  公开（公告）日：2006-09-26