4-(octahydro-2H-pyrido[1,2-a]pyrazin-2-yl)phenylamine | 915722-90-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(octahydro-2H-pyrido[1,2-a]pyrazin-2-yl)phenylamine
• 英文别名: 4-(dihydro-1H-pyrido[1,2-a]pyrazin-2(6H,7H,8H,9H,9aH)-yl)aniline；4-(1,3,4,6,7,8,9,9a-Octahydropyrido[1,2-a]pyrazin-2-yl)aniline
• CAS: 915722-90-6
• 化学式: C₁₄H₂₁N₃
• 分子量: 231.341
• InChiKey: CXQBYWWEFMGQBR-UHFFFAOYSA-N

物化性质

• 沸点：
  410.8±40.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(octahydro-2H-pyrido[1,2-a]pyrazin-2-yl)phenylamine 、 4-氯-2,3-二甲基喹啉 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 0.25h， 以21%的产率得到(2,3-dimethylquinolin-4-yl)-[4-(octahydro-2H-pyrido[1,2-a]-pyrazin-2-yl)phenyl]amine
  参考文献：
  名称：

  Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists

  摘要：

  Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C.)). A number of compounds with good antagonist potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4-dimethylpiperazin-1-yl) phenylamino] quinolin- 3- yl} methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.

  DOI：

  10.1021/jm060262x
• 作为产物：
  描述：

  八氢吡啶并[1,2-a]吡嗪 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 16.0h， 生成 4-(octahydro-2H-pyrido[1,2-a]pyrazin-2-yl)phenylamine
  参考文献：
  名称：

  [EN] PYRIMIDINE DERIVATIVES AS KINASE INHIBITORS AND THEIR THERAPEUTICAL APPLICATIONS
  [FR] DÉRIVÉS DE PYRIMIDINE UTILISÉS EN TANT QU'INHIBITEURS DE KINASE, ET LEURS APPLICATIONS THÉRAPEUTIQUES

  摘要：

  本发明提供了具有抗增殖活性的激酶抑制剂，包括取代嘧啶衍生物及其药用可接受的配方。此外，本发明提供了制备新化合物的方法以及使用这些化合物的方法。

  公开号：

  WO2016138527A1

文献信息

• TRICYCLIC INHIBITORS OF KINASES
  申请人：Tong Yunsong

  公开号：US20120220572A1

  公开（公告）日：2012-08-30

  The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein X, Y, Z, R 3 and R 4 are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as wee-1 and methods of treating diseases such as cancer.

  本发明涉及式(I)的化合物或药用可接受的盐，其中X、Y、Z、R3和R4在描述中有定义。本发明还涉及含有上述化合物的组合物，用于抑制wee-1等激酶，并治疗癌症等疾病的方法。
• [EN] PYRIMIDINE DERIVATIVES AS KINASE INHIBITORS AND THEIR THERAPEUTICAL APPLICATIONS<br/>[FR] DÉRIVÉS DE PYRIMIDINE UTILISÉS EN TANT QU'INHIBITEURS DE KINASE, ET LEURS APPLICATIONS THÉRAPEUTIQUES
  申请人：NANTBIOSCIENCE INC

  公开号：WO2016138527A1

  公开（公告）日：2016-09-01

  The present invention provides kinase inhibitors with anti-proliferative activity comprising substituted pyrimidine derivatives and pharmaceutically-acceptable formulations thereof. In addition, the invention provides methods for making novel compounds and methods for using the compounds.

  本发明提供了具有抗增殖活性的激酶抑制剂，包括取代嘧啶衍生物及其药用可接受的配方。此外，本发明提供了制备新化合物的方法以及使用这些化合物的方法。
• US8710065B2
  申请人：——

  公开号：US8710065B2

  公开（公告）日：2014-04-29
• [EN] TRICYCLIC INHIBITORS OF KINASES<br/>[FR] INHIBITEURS TRICYCLIQUES DE KINASES
  申请人：ABBOTT LAB

  公开号：WO2012161812A1

  公开（公告）日：2012-11-29

  The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, ( l ) wherein X, Y, Z, R3 and R4 are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as wee-1 and methods of treating diseases such as cancer.
• Structure−Activity Relationship of Quinoline Derivatives as Potent and Selective α_2C-Adrenoceptor Antagonists
  作者：Iisa P. J. Höglund、Satu Silver、Mia T. Engström、Harri Salo、Andrei Tauber、Hanna-Kaisa Kyyrönen、Pauli Saarenketo、Anna-Marja Hoffrén、Kurt Kokko、Katariina Pohjanoksa、Jukka Sallinen、Juha-Matti Savola、Siegfried Wurster、Oili A. Kallatsa

  DOI：10.1021/jm060262x

  日期：2006.10.1

  Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human alpha(2)-adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C.)). A number of compounds with good antagonist potencies against the alpha(2C)-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-4-[4-(3,4-dimethylpiperazin-1-yl) phenylamino] quinolin- 3- yl} methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the alpha(2C)-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the alpha(2C)-adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.