2-(S)-[6-benzylamino-9-isopropyl-(9H)-purin-2-yl]-amino-propanol

• 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: 2-(S)-[6-benzylamino-9-isopropyl-(9H)-purin-2-yl]-amino-propanol
• 英文别名: 2,6,9-Trisubstituted purine deriv. 20；(2S)-2-[[6-(benzylamino)-9-propan-2-ylpurin-2-yl]amino]propan-1-ol
• 化学式: C₁₈H₂₄N₆O
• 分子量: 340.428
• InChiKey: PEIHEIMZOKGNHC-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  87.9
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-chloro-2-iodo-9-isopropylpurine 在 三正丙胺 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基乙酰胺 为溶剂， 反应 27.0h， 生成 2-(S)-[6-benzylamino-9-isopropyl-(9H)-purin-2-yl]-amino-propanol
  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

• Nouveaux dérivés de purine possédant notamment des propriétés anti-prolifératives et leurs applications biologiques
  申请人：Centre National de la Recherche Scientifique (C.N.R.S.)

  公开号：EP1308447A1

  公开（公告）日：2003-05-07

  Les dérivés de l'invention sont des dérivés de purine substitués en positions 2, 6 et 9. Il s'agit en particulier de la 2-(1-R hydroxyméthylpropylamino)-6-benzylamino-9-isopropylpurine. Ces dérivés présentent notamment des propriétés antiprolifératives et sont utilisables comme médicaments et comme herbicide.

  本发明的衍生物是在第 2、6 和 9 位被取代的嘌呤衍生物。 特别是 2-(1-R-羟甲基丙基氨基)-6-苄基氨基-9-异丙基嘌呤。 这些衍生物具有抗增殖特性，可用作药物和除草剂。
• Purine derivatives for the treatment of cystic diseases
  申请人：GENZYME CORPORATION

  公开号：EP2617423A1

  公开（公告）日：2013-07-24

  Provided herein are methods of treatment of a cystic disease by administering a compound of Formula I. In certain embodiments, the compound for use in the methods provided herein is roscovitine or an analog thereof.

  本文提供了通过施用式 I 化合物治疗囊性疾病的方法。在某些实施例中，用于本文所提供方法的化合物是罗索维汀或其类似物。
• Purine derivatives having, in particular, antiproliferative properties, and their biological uses
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIGUE (C.N.R.S.)

  公开号：US20020049218A1

  公开（公告）日：2002-04-25

  This invention provides 2-, 6, and 9-substituted purine derivatives, particularly 2(1-R hydroxymethylpropylamino)-6-benzylamino-9-isopropyl purine, having, in particular, antiproliferative properties, and suitable for use as pharmaceutical compositions and herbicidal compositions. Also provided are pharmaceutical compositions and herbicidal compositions comprising the 2-, 6, and 9-substituted purine derivatives, and methods of treatment using the 2-, 6, and 9-substituted purine derivatives.

  本发明提供了 2-、6-和 9-取代的嘌呤衍生物，特别是 2(1-R羟甲基丙氨基)-6-苄氨基-9-异丙基嘌呤，尤其具有抗增殖特性，适合用作药物组合物和除草组合物。还提供了包含 2-、6-和 9-取代嘌呤衍生物的药物组合物和除草组合物，以及使用 2-、6-和 9-取代嘌呤衍生物的治疗方法。
• Purine derivatives having, in particular, anti-proliferative properties and their biological uses
  申请人：Centre National De La Recherche Scientifique (C.N.R.S.)

  公开号：US20040235868A1

  公开（公告）日：2004-11-25

  This invention provides 2-, 6, and 9-substituted purine derivatives, particularly 2(1-R hydroxymethylpropylamino)-6-benzylamino-9-isopropyl purine, having, in particular, antiproliferative properties, and suitable for use as pharmaceutical compositions and herbicidal compositions. Also provided are pharmaceutical compositions and herbicidal compositions comprising the 2-, 6, and 9-substituted purine derivatives, and methods of treatment using the 2-, 6, and 9-substituted purine derivatives.

  本发明提供了 2-、6-和 9-取代的嘌呤衍生物，特别是 2(1-R羟甲基丙氨基)-6-苄氨基-9-异丙基嘌呤，尤其具有抗增殖特性，适合用作药物组合物和除草组合物。还提供了包含 2-、6-和 9-取代嘌呤衍生物的药物组合物和除草组合物，以及使用 2-、6-和 9-取代嘌呤衍生物的治疗方法。
• [EN] NOVEL PURINE DERIVATIVES HAVING, IN PARTICULAR, ANTIPROLIFERATIVE PROPERTIES, AND BIOLOGICAL USES THEREOF<br/>[FR] NOUVEAUX DERIVES DE PURINE POSSEDANT NOTAMMENT DES PROPRIETES ANTI-PROLIFERATIVES ET LEURS APPLICATIONS BIOLOGIQUES
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (C.N.R.S.)

  公开号：WO1997020842A1

  公开（公告）日：1997-06-12

  (EN) 2-, 6- and 9-substituted purine derivatives, particularly 2-(1-R hydroxymethylpropylamino)-6-benzylamino-9-isopropylpurine, having, in particular, antiproliferative properties, and suitable for use as drugs and weedkillers, are disclosed.(FR) Les dérivés de l'invention sont des dérivés de purine substitués en positions 2, 6 et 9. Il s'agit en particulier de la 2-(1-R hydroxyméthylpropylamino)-6-benzylamino-9-isopropylpurine. Ces dérivés présentent notamment des propriétés anti-prolifératives et sont utilisables comme médicaments et comme herbicide.

  分别在2、6和9位取代的嘌呤衍生物，其中特别的是2-（1-R-羟甲基丙基氨基）-6-苯基氨基-9-甲基丙基嘌呤，这种嘌呤衍生物具有特别具有抑制癌细胞增殖的性质，并且可用于作为药物和除草剂。