ditert-butyl [(2R,3S,4R,5R)-5-[6-(cyclopentylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphate | 1386935-64-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: ditert-butyl [(2R,3S,4R,5R)-5-[6-(cyclopentylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphate
• CAS: 1386935-64-3
• 化学式: C₂₃H₃₈N₅O₇P
• 分子量: 527.558
• InChiKey: ICVADFSWRIJBLZ-QTQZEZTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  150
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  ditert-butyl [(2R,3S,4R,5R)-5-[6-(cyclopentylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphate 在 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 0.5h， 生成 disodium ((2R,3S,4R,5R)-5-(6-(cyclopentylamino)-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl phosphate
  参考文献：
  名称：

  Orally Active Adenosine A₁ Receptor Agonists with Antinociceptive Effects in Mice

  摘要：

  Adenosine A(1) receptor (A(1)AR) agonists have antinociceptive effects in multiple preclinical models of acute and chronic pain. Although numerous AIAR agonists have been developed, clinical applications of these agents have been hampered by their cardiovascular side effects. Herein we report a series of novel A(1)AR agonists, some of which are structurally related to adenosine 5'-monophosphate (5'-AMP), a naturally occurring nucleotide that itself activates A(1)AR These novel compounds potently activate A,AR in several orthogonal in vitro assays and are subtype selective for A(1)AR over A(2A)AR, A(2B)AR, and A(3)AR. Among them, UNC32A (3a) is orally active and has dose-dependent antinociceptive effects in wild-type mice. The antinociceptive effects of 3a were completely abolished in A(1)AR knockout mice, revealing a strict dependence on A(1)AR for activity. The apparent lack of cardiovascular side effects when administered orally and high affinity (K-i of 36 nM for the human A(1)AR) make this compound potentially suitable as a therapeutic.

  DOI：

  10.1021/jm3004834
• 作为产物：
  描述：

  N,N-二异丙基亚磷酰胺二叔丁酯 在 四氮唑 、 双氧水 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 生成 ditert-butyl [(2R,3S,4R,5R)-5-[6-(cyclopentylamino)purin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphate
  参考文献：
  名称：

  Orally Active Adenosine A₁ Receptor Agonists with Antinociceptive Effects in Mice

  摘要：

  Adenosine A(1) receptor (A(1)AR) agonists have antinociceptive effects in multiple preclinical models of acute and chronic pain. Although numerous AIAR agonists have been developed, clinical applications of these agents have been hampered by their cardiovascular side effects. Herein we report a series of novel A(1)AR agonists, some of which are structurally related to adenosine 5'-monophosphate (5'-AMP), a naturally occurring nucleotide that itself activates A(1)AR These novel compounds potently activate A,AR in several orthogonal in vitro assays and are subtype selective for A(1)AR over A(2A)AR, A(2B)AR, and A(3)AR. Among them, UNC32A (3a) is orally active and has dose-dependent antinociceptive effects in wild-type mice. The antinociceptive effects of 3a were completely abolished in A(1)AR knockout mice, revealing a strict dependence on A(1)AR for activity. The apparent lack of cardiovascular side effects when administered orally and high affinity (K-i of 36 nM for the human A(1)AR) make this compound potentially suitable as a therapeutic.

  DOI：

  10.1021/jm3004834