2-(4-(嘧啶-2-基)哌嗪-1-基)乙腈 | 33386-13-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 2-(4-(嘧啶-2-基)哌嗪-1-基)乙腈
• 英文名称: 1-(2-Pyrimidinyl)-4-cyanmethyl-piperazin
• 英文别名: 2-(4-(pyrimidin-2-yl)piperazin-1-yl)acetonitrile；(4-pyrimidin-2-yl-piperazin-1-yl)-acetonitrile；2-[4-(Pyrimidin-2-yl)piperazin-1-yl]acetonitrile；2-(4-pyrimidin-2-ylpiperazin-1-yl)acetonitrile
• CAS: 33386-13-9
• 化学式: C₁₀H₁₃N₅
• mdl: MFCD09906907
• 分子量: 203.247
• InChiKey: GNHNLTWAAXUZQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  56
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-(嘧啶-2-基)哌嗪-1-基)乙腈 在 氢气 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以97%的产率得到2-(4-(嘧啶-2-基)哌嗪-1-基)乙胺
  参考文献：
  名称：

  Further delineation of hydrophobic binding sites in dopamine D2/D3 receptors for N-4 substituents on the piperazine ring of the hybrid template 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol

  摘要：

  Here we report a structure-activity relationship (SAR) study of analogues of 5/7-{[2-(4-aryl-piperazin-1-yl)- ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol. Our SAR is focused on introduction of various substitutions in the piperazine ring of the hybrid template. The goal behind this study is to delineate the nature of the binding pocket for N-aryl substitution in the piperazine ring by observing the effect of various hydrophobic and other heteroaromatic substitutions on binding affinity (K-i), as measured with tritiated spiperone and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed with the GTP gamma S binding assay. Compound 8d was the most selective for the D-3 receptor in the spiperone binding assay. An interesting similarity in binding affinity was observed between isoquinoline derivative D-301 and the 2-substituted pyridine derivative 8d, suggesting the importance of relative spatial relationships between the N-atom of the ligand and the molecular determinants of the binding pocket in D-2/D-3 receptors. Functional activity assays demonstrated high potency and selectivity of (+)-8a and (-)-28b (D-2/D-3 (ratio of EC50): 105 and 202, respectively) for the D-3 receptor and both compounds were more selective compared to the reference drug ropinirole (D-2/D-3 (ratio of EC50): 29.5). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.025
• 作为产物：
  描述：

  1-(2-嘧啶基)哌嗪 、 溴乙腈 在 Intermediate 149.2 作用下， 生成 2-(4-(嘧啶-2-基)哌嗪-1-基)乙腈
  参考文献：
  名称：

  3-imidazolyl-indoles for the treatment of proliferative diseases

  摘要：

  本发明涉及式I的3-杂环基吲哚化合物，能够抑制p53或其变异体与MDM2和/或MDM4或其变异体之间的相互作用：其中R1，R2，R3，R4，RA，Y和Y如说明书所定义。由于其活性，这些化合物在治疗由MDM2和/或MDM4或其变异体活性介导的各种疾病和疾病，如炎症或增殖性疾病或细胞保护方面是有用的。

  公开号：

  US08053457B2

文献信息

• 3-Imidazolyl-Indoles for the Treatment of Proliferative Diseases
  申请人：Boettcher Andreas

  公开号：US20100125064A1

  公开（公告）日：2010-05-20

  The invention relates to 3-heterocyclyl indolyl compounds capable of inhibiting the interaction between p53, or variants thereof, and MDM2 and/or MDM4, or variants thereof, respectively, said compounds having the formula I, wherein R 1 , R 2 , R 3 , R 4 , R A , Y and Y are as defined in the specification. Due to their activity, the compounds are useful in the treatment of various disorders and diseases mediated by the activity of MDM2 and/or MDM4, or variants thereof, such as inflammatory or proliferative diseases or in the protection of cells.

  本发明涉及能够抑制p53或其变体与MDM2和/或MDM4或其变体相互作用的3-杂环基吲哚化合物，其中所述化合物具有式I，其中R1、R2、R3、R4、RA、Y和Y的定义见说明书。由于其活性，这些化合物可用于治疗由MDM2和/或MDM4或其变体介导的各种疾病和疾病，例如炎症性或增殖性疾病或细胞保护。
• 3-IMIDAZOLYL-INDOLES FOR THE TREATMENT OF PROLIFERATIVE DISEASES
  申请人：Novartis AG

  公开号：EP2142535A2

  公开（公告）日：2010-01-13
• US8053457B2
  申请人：——

  公开号：US8053457B2

  公开（公告）日：2011-11-08
• [EN] 3-IMIDAZOLYL-INDOLES FOR THE TREATMENT OF PROLIFERATIVE DISEASES<br/>[FR] 3-IMIDAZOLYL-INDOLES POUR LE TRAITEMENT DE MALADIES PROLIFÉRATIVES
  申请人：NOVARTIS AG

  公开号：WO2008119741A2

  公开（公告）日：2008-10-09

  [EN] The invention relates to 3-heterocyclyl indolyl compounds capable of inhibiting the interaction between p53, or variants thereof, and MDM2 and/or MDM4, or variants thereof, respectively, said compounds having the formula (I) wherein R¹, R², R³, R⁴, R^A, Y and Y are as defined in the specification. Due to their activity, the compounds are useful in the treatment of various disorders and diseases mediated by the activity of MDM2 and/or MDM4, or variants thereof, such as inflammatory or proliferative diseases or in the protection of cells.
  [FR] L'invention porte sur des composés 3-hétérocyclyl indolylés, capables d'inhiber l'interaction entre p53, ou des variantes de celui-ci, et MDM2 et/ou MDM4, ou des variantes de ceux-ci, respectivement, lesdits composés ayant la formule (I) dans laquelle R¹, R², R³, R⁴, R^A, Y et Y sont tels que définis dans la description. En raison de leur activité, les composés sont utiles dans le traitement de divers troubles et diverses maladies à médiation par l'activité de MDM2 et/ou MDM4, ou des variantes de ceux-ci, tels que des maladies inflammatoires ou prolifératives ou dans la protection de cellules.
• Further delineation of hydrophobic binding sites in dopamine D2/D3 receptors for N-4 substituents on the piperazine ring of the hybrid template 5/7-{[2-(4-aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol
  作者：Balaram Ghosh、Tamara Antonio、Bhaskar Gopishetty、Maarten Reith、Aloke Dutta

  DOI：10.1016/j.bmc.2010.06.025

  日期：2010.8

  Here we report a structure-activity relationship (SAR) study of analogues of 5/7-[2-(4-aryl-piperazin-1-yl)- ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-2-ol. Our SAR is focused on introduction of various substitutions in the piperazine ring of the hybrid template. The goal behind this study is to delineate the nature of the binding pocket for N-aryl substitution in the piperazine ring by observing the effect of various hydrophobic and other heteroaromatic substitutions on binding affinity (K-i), as measured with tritiated spiperone and HEK-293 cells expressing either D-2 or D-3 receptors. Functional activity of selected compounds was assessed with the GTP gamma S binding assay. Compound 8d was the most selective for the D-3 receptor in the spiperone binding assay. An interesting similarity in binding affinity was observed between isoquinoline derivative D-301 and the 2-substituted pyridine derivative 8d, suggesting the importance of relative spatial relationships between the N-atom of the ligand and the molecular determinants of the binding pocket in D-2/D-3 receptors. Functional activity assays demonstrated high potency and selectivity of (+)-8a and (-)-28b (D-2/D-3 (ratio of EC50): 105 and 202, respectively) for the D-3 receptor and both compounds were more selective compared to the reference drug ropinirole (D-2/D-3 (ratio of EC50): 29.5). (C) 2010 Elsevier Ltd. All rights reserved.