Benzyl-(2-iodo-9-isopropyl-9H-purin-6-yl)-amine | 247193-41-5

• 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: Benzyl-(2-iodo-9-isopropyl-9H-purin-6-yl)-amine
• 英文别名: 2,6,9-Trisubstituted purine deriv. 5c；N-benzyl-2-iodo-9-propan-2-ylpurin-6-amine
• CAS: 247193-41-5
• 化学式: C₁₅H₁₆IN₅
• 分子量: 393.23
• InChiKey: MKMXWDSWLHBSGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Benzyl-(2-iodo-9-isopropyl-9H-purin-6-yl)-amine 在 palladium on activated charcoal bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 氢气 、 正丁胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-(6-Benzylamino-9-isopropyl-9H-purin-2-yl)-butan-1-ol
  参考文献：
  名称：

  Synthesis of C2 alkynylated purines, a new family of potent inhibitors of cyclin-dependent kinases

  摘要：

  The synthesis of a new family of inhibitors of the cell cycle regulating cyclin-dependent kinases (CDK's) is reported. These compounds, related to the purines olomoucine and roscovitine, are characterised by the presence of alkynylated side chains at C2. They inhibit CDK's with IC50's in the 200 nM range. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00097-3
• 作为产物：
  描述：

  6-氯-9-异丙基-9H-嘌呤-2-胺 在 copper(l) iodide 、 二碘甲烷 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 生成 Benzyl-(2-iodo-9-isopropyl-9H-purin-6-yl)-amine
  参考文献：
  名称：

  Synthesis and in vitro evaluation of novel 2,6,9-trisubstituted purines acting as cyclin-dependent kinase inhibitors

  摘要：

  Novel C-2, C-6, N-9 trisubstituted purines derived from the olomoucine/roscovitine lead structure were synthesized and evaluated for their ability to inhibit starfish oocyte CDK1/cyclin B, neuronal CDK5/p35 and erk1 kinases in purified extracts. Structure-activity relationship studies showed that increased steric bulk at N-9 reduces the inhibitory potential whereas substitution of the aminoethanol C-2 side chain by various groups of different size (methyl, propyl, butyl, phenyl, benzyl) only slightly decreases the activity when compared to (R)-roscovitine. Optimal inhibitory activity against CDK5, CDK1 and CDK2, with IC50 values of 0.16, 0.45 and 0.65 mu M, respectively, was obtained with compound 21 containing a (2R)-pyrrolidin-2-yl-methanol substituent at the C-2 and a 3-iodobenzylamino group at the C-6 of the purine. Compound 21 proved cytotoxic against human tumor HeLa cells (LD50 = 6.7 mu M versus 42.7 mu M for olomoucine, 24-h contact). Furthermore, unlike olomoucine, compound 21 was effective upon short exposure (LD50 = 25.3 mu M, 2-h contact). The available data suggest that the affinity for CDKs and the cytotoxic potential of the drugs are inter-related. However, no straightforward cell cycle phase specificity of the cytotoxic response to 21 was observed in synchronized HeLa cells. With the noticeable exception of pronounced lengthening of the S-phase transit by 21 applied during early-S in synchronized HeLa cells, and in striking contrast with earlier reports on studies using plant or echinoderm cells, olomoucine and compound 21 were unable to reversibly arrest cell cycle progression in asynchronous growing HeLa cells. Some irreversible block in G1 and G2 phase occurred at high olomoucine concentration, correlated with induced cell death. Moreover, chronic exposure to lethal doses of compound 21 resulted in massive nuclear fragmentation, evocative of mitotic catastrophe with minor amounts of apoptosis only. It was also found that olomoucine and compound 21 reversibly block the intracellular uptake of nucleosides with high efficiency. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00064-4

文献信息

• Synthesis and in vitro evaluation of novel 2,6,9-trisubstituted purines acting as cyclin-dependent kinase inhibitors
  作者：Michel Legraverend、Odile Ludwig、Emile Bisagni、Sophie Leclerc、Laurent Meijer、Nicole Giocanti、Ramin Sadri、Vincent Favaudon

  DOI：10.1016/s0968-0896(99)00064-4

  日期：1999.7

  Novel C-2, C-6, N-9 trisubstituted purines derived from the olomoucine/roscovitine lead structure were synthesized and evaluated for their ability to inhibit starfish oocyte CDK1/cyclin B, neuronal CDK5/p35 and erk1 kinases in purified extracts. Structure-activity relationship studies showed that increased steric bulk at N-9 reduces the inhibitory potential whereas substitution of the aminoethanol C-2 side chain by various groups of different size (methyl, propyl, butyl, phenyl, benzyl) only slightly decreases the activity when compared to (R)-roscovitine. Optimal inhibitory activity against CDK5, CDK1 and CDK2, with IC50 values of 0.16, 0.45 and 0.65 mu M, respectively, was obtained with compound 21 containing a (2R)-pyrrolidin-2-yl-methanol substituent at the C-2 and a 3-iodobenzylamino group at the C-6 of the purine. Compound 21 proved cytotoxic against human tumor HeLa cells (LD50 = 6.7 mu M versus 42.7 mu M for olomoucine, 24-h contact). Furthermore, unlike olomoucine, compound 21 was effective upon short exposure (LD50 = 25.3 mu M, 2-h contact). The available data suggest that the affinity for CDKs and the cytotoxic potential of the drugs are inter-related. However, no straightforward cell cycle phase specificity of the cytotoxic response to 21 was observed in synchronized HeLa cells. With the noticeable exception of pronounced lengthening of the S-phase transit by 21 applied during early-S in synchronized HeLa cells, and in striking contrast with earlier reports on studies using plant or echinoderm cells, olomoucine and compound 21 were unable to reversibly arrest cell cycle progression in asynchronous growing HeLa cells. Some irreversible block in G1 and G2 phase occurred at high olomoucine concentration, correlated with induced cell death. Moreover, chronic exposure to lethal doses of compound 21 resulted in massive nuclear fragmentation, evocative of mitotic catastrophe with minor amounts of apoptosis only. It was also found that olomoucine and compound 21 reversibly block the intracellular uptake of nucleosides with high efficiency. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Synthesis of C2 alkynylated purines, a new family of potent inhibitors of cyclin-dependent kinases
  作者：Michel Legraverend、Odile Ludwig、Emile Bisagni、Sophie Leclerc、Laurent Meijer

  DOI：10.1016/s0960-894x(98)00097-3

  日期：1998.4

  The synthesis of a new family of inhibitors of the cell cycle regulating cyclin-dependent kinases (CDK's) is reported. These compounds, related to the purines olomoucine and roscovitine, are characterised by the presence of alkynylated side chains at C2. They inhibit CDK's with IC50's in the 200 nM range. (C) 1998 Elsevier Science Ltd. All rights reserved.