9-(3-aminopropyl)-2-methoxyadenine | 1178551-06-8

• 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-aminopropyl)-2-methoxyadenine
• 英文别名: 9-(3-Aminopropyl)-2-methoxypurin-6-amine
• CAS: 1178551-06-8
• 化学式: C₉H₁₄N₆O
• 分子量: 222.25
• InChiKey: HSGPCHHTGNEFQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  9-(3-aminopropyl)-2-methoxyadenine 、 Cbz-Leu-D,LPhe-COOH 在 1-羟基苯并三唑 、 1,2-二氯乙烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以24%的产率得到3-(benzyloxycarbonyl-L-leucylamino)-N-(3-(6-amino-2-methoxy-9H-purin-9-yl)propyl)-2-oxophenylbutanamide
  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-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

文献信息

• HETEROCYCLIC PEPTIDE KETOAMIDES
  申请人：Powers James C.

  公开号：US20110053858A1

  公开（公告）日：2011-03-03

  A novel class of peptide α-ketoamides useful for selectively inhibiting calpains, selectively inhibiting cysteine proteases, and generally inhibiting all cysteine proteases, having the formula M-AA 2 -AA 1 -CO—NH—(CH 2 ) n —R 3 . Processes for the synthesis of peptidyl α-ketoamide derivatives. Compositions and methods for inhibiting cysteine proteases, inhibiting calpains, and treating disease caused by cysteine proteases and calpains are provided

  一种新型的肽α-酮酰胺类化合物，可用于选择性抑制卡尔帕因酶、选择性抑制半胱氨酸蛋白酶和一般抑制所有半胱氨酸蛋白酶，其化学式为M-AA2-AA1-CO—NH—(CH2)n—R3。还提供了合成肽基α-酮酰胺衍生物的方法、抑制半胱氨酸蛋白酶、抑制卡尔帕因酶、治疗由半胱氨酸蛋白酶和卡尔帕因酶引起的疾病的组合物和方法。
• US8518885B2
  申请人：——

  公开号：US8518885B2

  公开（公告）日：2013-08-27
• [EN] HETEROCYCLIC PEPTIDE KETOAMIDES<br/>[FR] CÉTOAMIDES PEPTIDIQUES HÉTÉROCYCLIQUES
  申请人：GEORGIA TECH RES INST

  公开号：WO2009099416A1

  公开（公告）日：2009-08-13

  A novel class of peptide α-ketoamides useful for selectively inhibiting calpains, selectively inhibiting cysteine proteases, and generally inhibiting all cysteine proteases, having the formula M-AA2-AA1-CO-NH-(CH2)n-R3. Processes for the synthesis of peptidyl α-ketoamide derivatives. Compositions and methods for inhibiting cysteine proteases, inhibiting calpains, and treating disease caused by cysteine proteases and calpains are provided.