2-((S)-1-amino-2-butanol)-4-(N-benzylamino)-8-(1-methylethyl)pyrazolo[1,5-a]-1,3,5-triazine | 1099104-84-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 2-((S)-1-amino-2-butanol)-4-(N-benzylamino)-8-(1-methylethyl)pyrazolo[1,5-a]-1,3,5-triazine
• 英文别名: (S)-4-Benzylamino-2-[1-(hydroxymethyl)propylamino]-8-isopropylpyrazolo[1,5-a]-1,3,5-triazine；(2S)-2-{[4-(benzylamino)-8-(propan-2-yl)pyrazolo[1,5-a][1,3,5]triazin-2-yl]amino}butan-1-ol；(2S)-2-[[4-(benzylamino)-8-propan-2-ylpyrazolo[1,5-a][1,3,5]triazin-2-yl]amino]butan-1-ol
• CAS: 1099104-84-3
• 化学式: C₁₉H₂₆N₆O
• 分子量: 354.455
• InChiKey: SQUNOCMDMIQIQK-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  87.4
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (S)-(+)-2-氨基-1-丁醇 、 N-benzyl-8-isopropyl-2-(methylsulfonyl)pyrazolo[1,5-a][1,3,5]triazin-4-amine 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以67%的产率得到2-((S)-1-amino-2-butanol)-4-(N-benzylamino)-8-(1-methylethyl)pyrazolo[1,5-a]-1,3,5-triazine
  参考文献：
  名称：

  Pyrazolo[1,5-a]-1,3,5-triazine as a Purine Bioisostere: Access to Potent Cyclin-Dependent Kinase Inhibitor (R)-Roscovitine Analogue

  摘要：

  Pharmacological inhibitors of cyclin-dependent kinases (CDKs) have a wide therapeutic potential. Among the CDK inhibitors currently under clinical trials, the 2,6,9-trisubstituted purine (R)-roscovitine displays rather high selectivity, low toxicity, and promising antitumor activity. In an effort to improve this structure, we synthesized several bioisosteres of roscovitine. Surprisingly, one of them, pyrazolo[1,5-a]-1,3,5-triazine 7a (N-&-N1, GP0210), displayed significantly higher potency, compared to (R)-roscovitine and imidazo[2,1-f]-1,2,4-triazine 13 (N-&-N2, GP0212), at inhibiting various CDKs and at inducing cell death in a wide variety of human tumor cell lines. This approach may thus provide second generation analogues with enhanced biomedical potential.

  DOI：

  10.1021/jm801340z

文献信息

• Novel substituted pyrazolo[1,5 a]-1,3,5-triazine derivatives and their analogues, pharmaceutical compositions containing same, use thereof as medicine and methods for preparing same
  申请人：Bernard Philippe

  公开号：US20060106019A1

  公开（公告）日：2006-05-18

  The invention concerns novel substituted pyrazolo[1,5 A]-1,3,5-triazine derivatives and some of their structural analogues, and their therapeutic uses, more particularly for preventing and treating pathologies involving central and/or peripheral neuronal degeneration. The invention also concerns methods for preparing same and novel synthesis intermediates. The compounds of the invention correspond more particularly to general formulae (Ia) and (Ib).

  本发明涉及新的取代的吡唑并[1,5 A]-1,3,5-三嗪衍生物及其结构类似物，以及它们的治疗用途，尤其是用于预防和治疗涉及中枢和/或周围神经退行性病变的病理学。本发明还涉及制备这些化合物的方法和新的合成中间体。本发明的化合物尤其对应于一般式(Ia)和(Ib)。
• Novel substituted pyrazolo[1,5<I>A</I>]-1,3,5-Triazine derivatives and their analogues, pharmaceutical compositions containing same, use thereof as medicine and methods for preparing same
  申请人：Bernard Philippe

  公开号：US20090105261A1

  公开（公告）日：2009-04-23

  The invention relates to novel derivatives capable of increasing the synthesis and/or the release of neurotrophic factors, and therefore able to be used as a human or veterinary medicinal product. The invention also relates to methods for preparing the derivatives and also to the intermediates required for their synthesis.

  本发明涉及一种新型衍生物，能够增加神经营养因子的合成和/或释放，因此能够用作人类或兽医药物。本发明还涉及制备这些衍生物的方法，以及其合成所需的中间体。
• NOUVELLES PYRAZOLO(1,5-A)-1,3,5-TRIAZINES SUBSTITUEES ET LEURS ANALOGIQUES, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT, UTILISATION A TITRE DE MEDICAMENT ET PROCEDES POUR LEUR PREPARATION
  申请人：Greenpharma

  公开号：EP1525205A2

  公开（公告）日：2005-04-27
• [EN] NOVEL SUBSTITUTED PYRAZOLO[1,5 A]-1,3,5-TRIAZINE DERIVATIVES AND THEIR ANALOGUES, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, USE THEREOF AS MEDICINE AND METHODS FOR PREPARING SAME<br/>[FR] NOUVELLES PYRAZOLO[1,5-A]-1,3,5-TRIAZINES SUBSTITUEES ET LEURS ANALOGIQUES, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT, UTILISATION A TITRE DE MEDICAMENT ET PROCEDES POUR LEUR PREPARATION
  申请人：GREENPHARMA SAS

  公开号：WO2004011464A2

  公开（公告）日：2004-02-05

  L'invention concerne notamment de nouveaux dérivés de pyrazolo[1,5-a]-1,3,5-triazines ainsi que certains de leurs analogues structuraux et leurs applications dans le domaine thérapeutique tout particulièrement pour la prévention et le traitement de pathologies impliquant une dégénérescence des neurones centraux et/ou périphériques. Elle concerne également des procédés pour leur préparation et de nouveaux intermédiaires de synthèse. Les composés de l'invention répondent plus particulièrement aux formules générales (Ia) et (Ib).
• Pyrazolo[1,5-<i>a</i>]-1,3,5-triazine as a Purine Bioisostere: Access to Potent Cyclin-Dependent Kinase Inhibitor (<i>R</i>)-Roscovitine Analogue
  作者：Florence Popowycz、Guy Fournet、Cédric Schneider、Karima Bettayeb、Yoan Ferandin、Cyrile Lamigeon、Oscar M. Tirado、Silvia Mateo-Lozano、Vicente Notario、Pierre Colas、Philippe Bernard、Laurent Meijer、Benoît Joseph

  DOI：10.1021/jm801340z

  日期：2009.2.12

  Pharmacological inhibitors of cyclin-dependent kinases (CDKs) have a wide therapeutic potential. Among the CDK inhibitors currently under clinical trials, the 2,6,9-trisubstituted purine (R)-roscovitine displays rather high selectivity, low toxicity, and promising antitumor activity. In an effort to improve this structure, we synthesized several bioisosteres of roscovitine. Surprisingly, one of them, pyrazolo[1,5-a]-1,3,5-triazine 7a (N-&-N1, GP0210), displayed significantly higher potency, compared to (R)-roscovitine and imidazo[2,1-f]-1,2,4-triazine 13 (N-&-N2, GP0212), at inhibiting various CDKs and at inducing cell death in a wide variety of human tumor cell lines. This approach may thus provide second generation analogues with enhanced biomedical potential.