N-&-N 1 | 1075731-72-4

• 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: N-&-N 1
• 英文别名: 2-((R)-1-amino-2-butanol)-4-(N-benzylamino)-8-(1-methylethyl)pyrazolo[1,5-a]-1,3,5-triazine；N & N1, GP0210；(R)-4-Benzylamino-2-[1-(hydroxymethyl)propylamino]-8-isopropylpyrazolo[1,5-a]-1,3,5-triazine；(2R)-2-{[4-(benzylamino)-8-(1-methylethyl)pyrazolo[1,5-a][1,3,5]triazin-2-yl]amino}butan-1-ol；(2R)-2-[[4-(benzylamino)-8-propan-2-ylpyrazolo[1,5-a][1,3,5]triazin-2-yl]amino]butan-1-ol
• CAS: 1075731-72-4
• 化学式: C₁₉H₂₆N₆O
• 分子量: 354.455
• InChiKey: SQUNOCMDMIQIQK-OAHLLOKOSA-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：

  2-氨基丁醇 、 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56%的产率得到N-&-N 1
  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

• PYRAZOLO[1,5-A]-1,3,5-TRIAZINE DERIVATIVES, PREPARATION THEREOF, AND THERAPEUTIC USE THEREOF
  申请人：Meijer Laurent

  公开号：US20120184557A1

  公开（公告）日：2012-07-19

  A compound of formula (I), or a pharmaceutically acceptable salt thereof, where R 1 is a (C 1 -C 6 )alkyl or (C 3 -C 6 )cycloalkyl group; R 2 is a (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkenyl, (C 1 -C 6 )fluoroalkyl, (C 1 -C 3 )fluoroalkoxy, or (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl group, substituted: (i) with one to three hydroxyl groups, or (ii) with an NR a R b group, where R a and R b are independently a hydrogen atom or a (C 1 -C 3 )alkyl group; or a pyrrolidinylmethyl group substituted with one to three hydroxyl groups; R 9 is the same as R 2 or hydrogen; the R 2 and R 9 groups independently being substitutable with an —OCOR 3 group, where R 3 is a natural or unnatural amino acid derivative or a piperidyl group; alternatively, R 2 and R 9 together form a heterocyclic compound; X and Y are independently a substitutable phenyl or heteroaryl group, the heteroaryl group being a thienyl, pyridyl, pyrimidinyl, thiazolyl, pyrrolyl, or furanyl group; and R 6 is a hydrogen or a (C 1 -C 3 )alkyl group.

  化合物的化学式（I）或其药用可接受的盐，其中R1是（C1-C6）烷基或（C3-C6）环烷基；R2是（C1-C6）烷基，（C3-C6）环烷基，（C1-C6）烯基，（C1-C6）氟烷基，（C1-C3）氟烷氧基或（C1-C6）烷氧（C1-C6）烷基，取代：（i）具有一到三个羟基，或（ii）具有NRaRb基团，其中Ra和Rb独立地是氢原子或（C1-C3）烷基；或者取代有一到三个羟基的吡咯甲基基团；R9与R2或氢相同；R2和R9基团可独立地被取代为—OCOR3基团，其中R3是天然或非天然氨基酸衍生物或哌啶基团；或者，R2和R9共同形成一个杂环化合物；X和Y是可独立取代的苯基或杂芳基，杂芳基是噻吩基，吡啶基，嘧啶基，噻唑基，吡咯基或呋喃基；R6是氢或（C1-C3）烷基。
• 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。
• DERIVÉS DE PYRAZOLO[1,5-A]-1,3,5-TRIAZINES, LEUR PREPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
  申请人：Centre National de la Recherche Scientifique (C.N.R.S.)

  公开号：EP2406263B1

  公开（公告）日：2013-09-25
• REGULATED BIOCIRCUIT SYSTEMS
  申请人：Obsidian Therapeutics, Inc.

  公开号：US20190192691A1

  公开（公告）日：2019-06-27

  The present invention provides regulatable biocircuit systems. Such systems provide modular and tunable protein expression systems in support of the discovery and development of therapeutic modalities.