9-[(3aR,4R,6S,6aS)-6-[(2-fluorophenyl)sulfanylmethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-N-cyclopentylpurin-6-amine | 581106-44-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-[(3aR,4R,6S,6aS)-6-[(2-fluorophenyl)sulfanylmethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-N-cyclopentylpurin-6-amine
• CAS: 581106-44-7
• 化学式: C₂₄H₂₈FN₅O₃S
• 分子量: 485.582
• InChiKey: VXGFWCXTHKYBSB-UGTJMOTHSA-N

物化性质

• 沸点：
  663.0±65.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  9-[(3aR,4R,6S,6aS)-6-[(2-fluorophenyl)sulfanylmethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-N-cyclopentylpurin-6-amine 在 溶剂黄146 作用下， 生成 N6-cyclopentyl-9H-[5-deoxy-5-(2-fluorophenylthio)-β-D-ribofuranosyl]adenine
  参考文献：
  名称：

  Structure–affinity relationships of 5 ′ -aromatic ethers and 5 ′ -aromatic sulfides as partial A 1 adenosine agonists, potential supraventricular anti-arrhythmic agents

  摘要：

  Atrial fibrillation (AF) is the most commonly encountered sustained clinical arrhythmia with an estimated 2.3 million cases in the US (2001). A, adenosine receptor agonists can slow the electrical impulse propagation through the atrioventricular (AV) node (i.e., negative dromotropic effect) resulting in prolongation of the stimulus-to-His bundle (S-H) interval to potentially reduce ventricular rate. Compounds that are full agonists of the A, adenosine receptor can cause high grade AV block. Therefore, it is envisioned that a compound that is a partial agonist of the A, adenosine receptor could avoid this deleterious effect. 5' Phenyl sulfides (e.g., 17, EC50 = 1.26 muM) and phenyl ethers (e.g., 28, EC50 = 0.2 muM) are partial agonists with respect to their AV nodal effects in guinea pig isolated hearts. Additional affinity, GTPgammaS binding data suggesting partial activity of the A(1) adenosine receptor, and PK results for 5' modified adenosine derivatives are shown. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.04.096
• 作为产物：
  描述：

  N6-环戊基腺苷酸 在 偶氮二甲酸二异丙酯 、 polystyrene bound triphenylphosphine 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 9-[(3aR,4R,6S,6aS)-6-[(2-fluorophenyl)sulfanylmethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-N-cyclopentylpurin-6-amine
  参考文献：
  名称：

  Structure–affinity relationships of 5 ′ -aromatic ethers and 5 ′ -aromatic sulfides as partial A 1 adenosine agonists, potential supraventricular anti-arrhythmic agents

  摘要：

  Atrial fibrillation (AF) is the most commonly encountered sustained clinical arrhythmia with an estimated 2.3 million cases in the US (2001). A, adenosine receptor agonists can slow the electrical impulse propagation through the atrioventricular (AV) node (i.e., negative dromotropic effect) resulting in prolongation of the stimulus-to-His bundle (S-H) interval to potentially reduce ventricular rate. Compounds that are full agonists of the A, adenosine receptor can cause high grade AV block. Therefore, it is envisioned that a compound that is a partial agonist of the A, adenosine receptor could avoid this deleterious effect. 5' Phenyl sulfides (e.g., 17, EC50 = 1.26 muM) and phenyl ethers (e.g., 28, EC50 = 0.2 muM) are partial agonists with respect to their AV nodal effects in guinea pig isolated hearts. Additional affinity, GTPgammaS binding data suggesting partial activity of the A(1) adenosine receptor, and PK results for 5' modified adenosine derivatives are shown. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.04.096

文献信息

• ABCA-1 ELEVATING COMPOUNDS AND METHODS
  申请人：Dhalla Arvinder

  公开号：US20090203689A1

  公开（公告）日：2009-08-13

  Disclosed are novel compounds of Formula I useful for treating various disease states, in particular, insulin resistance, diabetes, dyslipidemia, coronary artery disease, and inflammation. The compounds of the present invention elevate cellular expression of the ABCA-1 gene as well as increasing the level of ABCA-1 protein, which may result in an increase in HDL levels in the plasma of a mammal, in particular humans.

  本发明公开了一种公式I的新化合物，用于治疗各种疾病状态，特别是胰岛素抵抗、糖尿病、血脂异常、冠状动脉疾病和炎症。本发明的化合物提高了ABCA-1基因的细胞表达，同时增加了ABCA-1蛋白的水平，这可能导致哺乳动物，特别是人类血浆中HDL水平的增加。
• Partial and full agonists of A1 adenosine receptors
  申请人：Dhalla Arvinder

  公开号：US20070185051A1

  公开（公告）日：2007-08-09

  Disclosed are novel compounds a compound of Formula I that are partial and full A 1 adenosine receptor agonists, useful for treating various disease states, in particular dyslipidemia, diabetes, decreased insulin sensitivity, Polycystic Ovarian Syndrome, Stein-Leventhal syndrome, and obesity.

  本发明涉及一种新型化合物，其中化合物I的部分和全A1腺苷受体激动剂，可用于治疗各种疾病状态，特别是血脂异常、糖尿病、胰岛素敏感性降低、多囊卵巢综合征、斯坦-莱文塔尔综合征和肥胖症。
• PARTIAL AND FULL AGONISTS OF A1 ADENOSINE RECEPTORS
  申请人：Dhalla Arvinder

  公开号：US20090247557A1

  公开（公告）日：2009-10-01

  Disclosed are novel compounds a compound of Formula I that are partial and full A 1 adenosine receptor agonists, useful for treating various disease states, in particular dyslipidemia, diabetes, decreased insulin sensitivity, Polycystic Ovarian Syndrome, Stein-Leventhal syndrome, and obesity.

  本发明涉及一种新型化合物，其中化合物I的部分和完全A1腺苷受体激动剂，可用于治疗各种疾病状态，特别是血脂异常、糖尿病、胰岛素敏感性降低、多囊卵巢综合症、斯坦 - 莱文塔尔综合症和肥胖症。
• US7157440B2
  申请人：——

  公开号：US7157440B2

  公开（公告）日：2007-01-02
• US7655638B2
  申请人：——

  公开号：US7655638B2

  公开（公告）日：2010-02-02