9-(3-azidopropyl)-2-methoxyadenine | 1241981-17-8

• 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-(3-azidopropyl)-2-methoxyadenine
• 英文别名: 9-(3-Azidopropyl)-2-methoxypurin-6-amine；9-(3-azidopropyl)-2-methoxypurin-6-amine
• CAS: 1241981-17-8
• 化学式: C₉H₁₂N₈O
• 分子量: 248.247
• InChiKey: YXGXJJPGSBIYTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  93.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  9-(3-azidopropyl)-2-methoxyadenine 在 5% Pd(II)/C(eggshell) 、 氢气 作用下， 以 甲醇 为溶剂， 反应 20.0h， 以75%的产率得到9-(3-aminopropyl)-2-methoxyadenine
  参考文献：
  名称：

  Peptidyl α-Ketoamides with Nucleobases, Methylpiperazine, and Dimethylaminoalkyl Substituents as Calpain Inhibitors

  摘要：

  A series of peptidyl alpha-ketoamides with the general structure Cbz-L-Leu-D,L-AA-CONH-R were synthesized and evaluated as inhibitors for the cystcine proteases calpain I, calpain II, and cathepsin B. Nucleobases, methylpiperazine, and dimethylaminoalkyl groups were incorporated into the primed region of the inhibitors to generate compounds that potentially cross the blood-brain barrier. Two of these compounds (Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-adenin-9-yl and Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-(4-methylpiperazin- l -yl) have been shown to have useful concentrations in the brain in animals. The best inhibitor for calpain I was Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-2-methoxyadenin-9-yl (K-i = 23 nM), and the best inhibitor for calpain II was Cbz-Leu-D,L-Phe-CONH-(CH2)(3)-adenin-9-yl (K-i = 68 nM). On the basis of the crystal structure obtained with heterocyclic peptidyl alpha-ketoamides, we have improved inhibitor potency by introducing a small hydrophobic group on the adenine ring. These inhibitors have good potential to be used in the treatment of neurodegenerative diseases.

  DOI：

  10.1021/jm901221v
• 作为产物：
  描述：

  9-(3-chloropropyl)-2-methoxyadenine 在 sodium azide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以74%的产率得到9-(3-azidopropyl)-2-methoxyadenine
  参考文献：
  名称：

  Peptidyl α-Ketoamides with Nucleobases, Methylpiperazine, and Dimethylaminoalkyl Substituents as Calpain Inhibitors

  摘要：

  A series of peptidyl alpha-ketoamides with the general structure Cbz-L-Leu-D,L-AA-CONH-R were synthesized and evaluated as inhibitors for the cystcine proteases calpain I, calpain II, and cathepsin B. Nucleobases, methylpiperazine, and dimethylaminoalkyl groups were incorporated into the primed region of the inhibitors to generate compounds that potentially cross the blood-brain barrier. Two of these compounds (Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-adenin-9-yl and Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-(4-methylpiperazin- l -yl) have been shown to have useful concentrations in the brain in animals. The best inhibitor for calpain I was Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-2-methoxyadenin-9-yl (K-i = 23 nM), and the best inhibitor for calpain II was Cbz-Leu-D,L-Phe-CONH-(CH2)(3)-adenin-9-yl (K-i = 68 nM). On the basis of the crystal structure obtained with heterocyclic peptidyl alpha-ketoamides, we have improved inhibitor potency by introducing a small hydrophobic group on the adenine ring. These inhibitors have good potential to be used in the treatment of neurodegenerative diseases.

  DOI：

  10.1021/jm901221v

文献信息

• Peptidyl α-Ketoamides with Nucleobases, Methylpiperazine, and Dimethylaminoalkyl Substituents as Calpain Inhibitors
  作者：Asli Ovat、Zhao Zhao Li、Christina Y. Hampton、Seneshaw A. Asress、Facundo M. Fernández、Jonathan D. Glass、James C. Powers

  DOI：10.1021/jm901221v

  日期：2010.9.9

  A series of peptidyl alpha-ketoamides with the general structure Cbz-L-Leu-D,L-AA-CONH-R were synthesized and evaluated as inhibitors for the cystcine proteases calpain I, calpain II, and cathepsin B. Nucleobases, methylpiperazine, and dimethylaminoalkyl groups were incorporated into the primed region of the inhibitors to generate compounds that potentially cross the blood-brain barrier. Two of these compounds (Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-adenin-9-yl and Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-(4-methylpiperazin- l -yl) have been shown to have useful concentrations in the brain in animals. The best inhibitor for calpain I was Cbz-Leu-D,L-Abu-CONH-(CH2)(3)-2-methoxyadenin-9-yl (K-i = 23 nM), and the best inhibitor for calpain II was Cbz-Leu-D,L-Phe-CONH-(CH2)(3)-adenin-9-yl (K-i = 68 nM). On the basis of the crystal structure obtained with heterocyclic peptidyl alpha-ketoamides, we have improved inhibitor potency by introducing a small hydrophobic group on the adenine ring. These inhibitors have good potential to be used in the treatment of neurodegenerative diseases.