1-(4-(4-acetylpiperazin-1-yl)phenyl)guanidine | 693230-06-7

• 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: 1-(4-(4-acetylpiperazin-1-yl)phenyl)guanidine
• 英文别名: 1-(4-(acetylpiperazin-1-yl)phenyl)guanidine；N-[4-(4-acetyl-piperazin-1-yl)-phenyl]-guanidine；N-[4-(4-acetylpiperazin-1-yl)phenyl]guanidine；2-[4-(4-acetylpiperazin-1-yl)phenyl]guanidine
• CAS: 693230-06-7
• 化学式: C₁₃H₁₉N₅O
• 分子量: 261.327
• InChiKey: MSILSEAASITEGZ-UHFFFAOYSA-N

物化性质

• 沸点：
  483.4±55.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  88
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N'-(5-(3-(dimethylamino)acryloyl)-4-methylthiazol-2-yl)-N,N-dimethylformimid amide 、 1-(4-(4-acetylpiperazin-1-yl)phenyl)guanidine 以 乙腈 为溶剂， 生成 1-(4-(4-(4-(2-amino-4-methylthiazol-5-yl)pyrimidin-2-ylamino)phenyl)piperazin-1-yl)ethanone
  参考文献：
  名称：

  2-substituted-4-heteroaryl-pyrimidines useful for the treatment of proliferative disorders

  摘要：

  本发明涉及选定的取代嘧啶及其制备方法，含有它们的制药组合物以及它们作为一种或多种蛋白激酶抑制剂的用途，因此可用于治疗增殖性疾病、病毒性疾病和/或其他疾病。

  公开号：

  US20090137572A1
• 作为产物：
  描述：

  氰胺 、 1-乙酰基-4-(4-氨基苯基)哌嗪 在 三甲基氯硅烷 作用下， 生成 1-(4-(4-acetylpiperazin-1-yl)phenyl)guanidine
  参考文献：
  名称：

  Synthesis, structure–activity relationship and biological evaluation of 2,4,5-trisubstituted pyrimidine CDK inhibitors as potential anti-tumour agents

  摘要：

  A series of 2,4,5-trisubstituted pyrimidines have been synthesised and characterised, which exhibited potent CDK inhibition and anti-proliferative activities. The structure activity relationship is analysed and a rational for CDK9 selectivity is discussed. Compound 9s, possessing appreciable selectivity for CDK9 over other CDKs, is capable of activating caspase 3, reducing the level of Mcl-1 anti-apoptotic protein, and inducing cancer cell apoptosis. Crown Copyright (C) 2013 Published by Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.08.052

文献信息

• Substituted 4-(Thiazol-5-yl)-2-(phenylamino)pyrimidines Are Highly Active CDK9 Inhibitors: Synthesis, X-ray Crystal Structures, Structure–Activity Relationship, and Anticancer Activities
  作者：Hao Shao、Shenhua Shi、Shiliang Huang、Alison J. Hole、Abdullahi Y. Abbas、Sonja Baumli、Xiangrui Liu、Frankie Lam、David W. Foley、Peter M. Fischer、Martin Noble、Jane A. Endicott、Chris Pepper、Shudong Wang

  DOI：10.1021/jm301475f

  日期：2013.2.14

  Cancer cells often have a high demand for antiapoptotic proteins in order to resist programmed cell death. CDK9 inhibition selectively targets survival proteins and reinstates apoptosis in cancer cells. We designed a series of 4-thiazol-2-anilinopyrimidine derivatives with functional groups attached to the CS-position of the pyrimidine or to the C4-thiazol moiety and investigated their effects on CDK9 potency and selectivity. One of the most selective compounds, 12u inhibits CDK9 with IC50 = 7 nM and shows over 80-fold selectivity for CDK9 versus CDK2. X-ray crystal structures of 12u bound to CDK9 and CDK2 provide insights into the binding modes. This work, together with crystal structures of selected inhibitors in complex with both enzymes described in a companion paper,(34) provides a rationale for the observed SAR. 12u demonstrates potent anticancer activity against primary chronic lymphocytic leukemia cells with a therapeutic window 31- and 107-fold over those of normal B-and T-cells.
• [EN] 2-SUBSTITUTED-4-HETEROARYL-PYRIMIDINES USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISORDERS<br/>[FR] COMPOSES
  申请人：CYCLACEL LTD

  公开号：WO2005116025A3

  公开（公告）日：2006-02-23
• Imidazole piperazines: SAR and development of a potent class of cyclin-dependent kinase inhibitors with a novel binding mode
  作者：M. Raymond V. Finlay、David G. Acton、David M. Andrews、Andrew J. Barker、Michael Dennis、Eric Fisher、Mark A. Graham、Clive P. Green、David W. Heaton、Galith Karoutchi、Sarah A. Loddick、Rémy Morgentin、Andrew Roberts、Julie A. Tucker、Hazel M. Weir

  DOI：10.1016/j.bmcl.2008.06.027

  日期：2008.8

  A piperazine series of cyclin-dependent kinase (CDK) inhibitors have been identified. The compounds exhibit excellent physiochemical properties and a novel binding mode, whereby a bridging interaction via a water molecule with Asp 86 of CDK2, leads to selectivity for the CDK family of enzymes over other kinases. Piperazines 2e and 2i were subsequently shown to inhibit tumour growth when dosed orally in a nude mouse xenograft study. Additional chemical series that exploit this unexpected interaction with Asp 86 are also described.
• WO2007/132220
  申请人：——

  公开号：——

  公开（公告）日：——
• 2-SUBSTITUTED-4-HETEROARYL-PYRIMIDINES USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
  申请人：Cyclacel Limited

  公开号：EP1756098A2

  公开（公告）日：2007-02-28