N-[2-chloro-9-(tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycine | 1185198-27-9

• 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: N-[2-chloro-9-(tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycine
• 英文别名: 2-[[2-Chloro-9-(oxan-2-yl)purin-6-yl]-cyclopropylamino]acetic acid
• CAS: 1185198-27-9
• 化学式: C₁₅H₁₈ClN₅O₃
• 分子量: 351.793
• InChiKey: AQOPZPARBCPUJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[2-chloro-9-(tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycine 、 3-苯基-L-丙氨酸苄酯 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 50.0h， 生成 N-[2-chloro-9-(tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycyl-L-phenylalanine benzyl ester
  参考文献：
  名称：

  一类新的取代嘌呤与Gly-AA-OBzl的偶联物：口服镇痛活性的合成和评价

  摘要：

  针对慢性疼痛的化学疗法，通过五步反应方法和19种新型缀合物N- [2-氯-9-（四氢吡喃-2-）偶联了两种止痛药，取代的嘌呤和Gly-AA-OBzl。提供了（yl）-9 H-嘌呤-6-yl] -N-环丙基糖基氨基酸苄酯。在鼠尾轻弹模型上，测定了它们的体内止痛活性。结果表明，将Gly-OC 2 H 5引入取代的嘌呤的6-位导致镇痛活性的模棱两可的增加，而将Gly-AA-OBzl引入该位置导致镇痛活性的显着增加。

  DOI：

  10.1016/j.bmcl.2009.05.077
• 作为产物：
  描述：

  N-[2-chloro-9-(tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycine ethyl ester 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以99%的产率得到N-[2-chloro-9-(tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycine
  参考文献：
  名称：

  一类新的取代嘌呤与Gly-AA-OBzl的偶联物：口服镇痛活性的合成和评价

  摘要：

  针对慢性疼痛的化学疗法，通过五步反应方法和19种新型缀合物N- [2-氯-9-（四氢吡喃-2-）偶联了两种止痛药，取代的嘌呤和Gly-AA-OBzl。提供了（yl）-9 H-嘌呤-6-yl] -N-环丙基糖基氨基酸苄酯。在鼠尾轻弹模型上，测定了它们的体内止痛活性。结果表明，将Gly-OC 2 H 5引入取代的嘌呤的6-位导致镇痛活性的模棱两可的增加，而将Gly-AA-OBzl引入该位置导致镇痛活性的显着增加。

  DOI：

  10.1016/j.bmcl.2009.05.077

文献信息

• N-[2-Chloro-9H-purin-6-yl]-N-cyclopropylglycylamino acids and derivatives: Synthesis, evaluation as a class of novel analgesics, and 3D QSAR analysis
  作者：Jinghua Zhao、Guifeng Kang、Wei Wang、Ming Zhao、Xiaoyi Zhang、Chunbo Lu、Wei Mao、Heng Wei Chang、Weidong Ye、Shiqi Peng

  DOI：10.1016/j.bmc.2009.07.035

  日期：2009.9.1

  Via a five-step-reaction procedure for the preparation of 19 known N-[2-chloro-9-(tetrahydropyran-2-yl)- 9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters (6a-s) and successive removal of 9-(tetrahydropyran- 2-yl) and benzylester groups 19 novel N-[2-chloro-9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters (7a-s) and 19 novel N-[2-chloro-9H-purin-6-yl]-N-cyclopropylglycylamino acids (8a-s) were provided. On tail-flick mouse model the in vivo analgesic activities of these 38 novel compounds were measured and most of them were defined as good analgesics. Based on Molecular Field Analysis of the pain threshold variations of the mice receiving 48 compounds in terms of the descriptors proton and methyl an equation was established. The data points (n), correlation coefficient (r), and square correlation coefficient (r(2)) of this equation were 48, 0.923, and 0.852, respectively. Using this equation pain threshold variations of 9 compounds were predicted and the errors ranged from 1.71 to 8.92. (C) 2009 Elsevier Ltd. All rights reserved.
• A class of novel conjugates of substituted purine and Gly-AA-OBzl: Synthesis and evaluation of orally analgesic activity
  作者：Guifeng Kang、Ming Zhao、Xiaoyi Zhang、Li Peng、Chunbo Li、Wei Mao、Weidong Ye、Shiqi Peng

  DOI：10.1016/j.bmcl.2009.05.077

  日期：2010.10

  five-step-reaction procedure and 19 novel conjugates N-[2-chloro-9-(tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters were provided. On mouse-tail flick model their in vivo analgesic activities were assayed. The results indicate that introducing Gly-OC2H5 into the 6-position of the substituted purine leads to ambiguous increase of the analgesic activity, while introducing Gly-AA-OBzl

  针对慢性疼痛的化学疗法，通过五步反应方法和19种新型缀合物N- [2-氯-9-（四氢吡喃-2-）偶联了两种止痛药，取代的嘌呤和Gly-AA-OBzl。提供了（yl）-9 H-嘌呤-6-yl] -N-环丙基糖基氨基酸苄酯。在鼠尾轻弹模型上，测定了它们的体内止痛活性。结果表明，将Gly-OC 2 H 5引入取代的嘌呤的6-位导致镇痛活性的模棱两可的增加，而将Gly-AA-OBzl引入该位置导致镇痛活性的显着增加。