6-氯-9-(3-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤 | 849241-91-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 6-氯-9-(3-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤
• 英文名称: 6-chloro-9H-(3-C-methyl-β-D-ribofuranosyl)purine
• 英文别名: 6-chloro-9-(3-C-methyl-β-D-ribofuranosyl)purine；6-Chloro-9-(3-C-methyl-b-D-ribofuranosyl)-9H-purine；(2R,3S,4R,5R)-5-(6-chloropurin-9-yl)-2-(hydroxymethyl)-3-methyloxolane-3,4-diol
• CAS: 849241-91-4
• 化学式: C₁₁H₁₃ClN₄O₄
• 分子量: 300.702
• InChiKey: GLZZDIVAKKZUKU-ZGUVBZSNSA-N

物化性质

• 密度：
  1.86

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 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：
  114
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-氯-9-(3-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤 在 羟胺 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以75%的产率得到N6-hydroxy-9-(3-C-methyl-β-D-ribofuranosyl)adenine
  参考文献：
  名称：

  Synthesis and biological activity of novel N6-substituted and 2,N6-disubstituted adenine ribo- and 3′-C-methyl-ribonucleosides as antitumor agents

  摘要：

  A series of N-6-aminopurine-9-beta-D-ribonucleosides and ribose-modified 3'-C-methyl analogues substituted at N-6-position with a small group like hydroxy, methoxy or amino group or at C2(N-6) position have been synthesized and tested against a panel of human leukemia and carcinoma cell lines. N-6-Hydrazino-9-beta-D-ribofuranosyl-Purine (5) displayed the best antiproliferative activity in the low micromolar or submicromolar range against all tested tumor cell lines. The activity of this nucleoside is related in part to ribonucleotide reductase inhibition. C2-modification or 3'-C-methylation in N-6-substituted adenosine analogues leads to a decrease or loss in activity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.055
• 作为产物：
  描述：

  6-chloro-9H-(2,3-di-O-acetyl-5-O-benzoyl-3-C-methyl-β-D-ribofuranosyl)purine 在 甲醇 、 氨 作用下， 生成 6-氯-9-(3-C-甲基-beta-D-呋喃核糖基)-9H-嘌呤
  参考文献：
  名称：

  Synthesis and biological activity of novel N6-substituted and 2,N6-disubstituted adenine ribo- and 3′-C-methyl-ribonucleosides as antitumor agents

  摘要：

  A series of N-6-aminopurine-9-beta-D-ribonucleosides and ribose-modified 3'-C-methyl analogues substituted at N-6-position with a small group like hydroxy, methoxy or amino group or at C2(N-6) position have been synthesized and tested against a panel of human leukemia and carcinoma cell lines. N-6-Hydrazino-9-beta-D-ribofuranosyl-Purine (5) displayed the best antiproliferative activity in the low micromolar or submicromolar range against all tested tumor cell lines. The activity of this nucleoside is related in part to ribonucleotide reductase inhibition. C2-modification or 3'-C-methylation in N-6-substituted adenosine analogues leads to a decrease or loss in activity. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.055

文献信息

• Synthesis, Biological Evaluation, and Molecular Modeling of Ribose-Modified Adenosine Analogues as Adenosine Receptor Agonists
  作者：Loredana Cappellacci、Palmarisa Franchetti、Michela Pasqualini、Riccardo Petrelli、Patrizia Vita、Antonio Lavecchia、Ettore Novellino、Barbara Costa、Claudia Martini、Karl-Norbert Klotz、Mario Grifantini

  DOI：10.1021/jm049408n

  日期：2005.3.1

  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.