N2-(2-chloro-benzyl)-5-nitro-N4-piperidin-4-ylmethyl-pyrimidine-2,4-diamine | 736053-73-9

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: N2-(2-chloro-benzyl)-5-nitro-N4-piperidin-4-ylmethyl-pyrimidine-2,4-diamine
• 英文别名: N2-(2-chlorobenzyl)-5-nitro-N4-(piperidin-4-ylmethyl)pyrimidine-2,4-diamine；2-N-[(2-chlorophenyl)methyl]-5-nitro-4-N-(piperidin-4-ylmethyl)pyrimidine-2,4-diamine
• CAS: 736053-73-9
• 化学式: C₁₇H₂₁ClN₆O₂
• 分子量: 376.846
• InChiKey: COCZJEZLXFFSJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N2-(2-chloro-benzyl)-5-nitro-N4-piperidin-4-ylmethyl-pyrimidine-2,4-diamine 生成 4-{[2-(2-chloro-benzylamino)-5-nitro-pyrimidin-4-ylamino]-methyl}-piperidine-1-carboxamidine
  参考文献：
  名称：

  Pyrimidine derivatives useful as inhibitors of PKC-theta

  摘要：

  揭示了一种新的化合物，其化学式为（I）：其中R1、R2和R3如本文所定义，这些化合物可用作PKC-theta的抑制剂，因此可用于治疗通过PKC-theta活性介导或维持的各种疾病和疾病，包括免疫性疾病和2型糖尿病。本发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和疾病的方法，制备这些化合物的工艺以及在这些工艺中有用的中间体。

  公开号：

  US20050124640A1
• 作为产物：
  描述：

  [2-[(2-Chlorophenyl)methylamino]-5-nitropyrimidin-4-yl] thiocyanate 、 4-氨甲基哌啶 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 N2-(2-chloro-benzyl)-5-nitro-N4-piperidin-4-ylmethyl-pyrimidine-2,4-diamine
  参考文献：
  名称：

  Discovery of potent and selective PKC-θ inhibitors

  摘要：

  An uHTS campaign was performed to identify selective inhibitors of PKC-theta. Initial triaging of the hit set based on selectivity and historical analysis led to the identification of 2,4-diamino-5-nitropyrimidines as potent and selective PKC-theta inhibitors. A homology model and initial SAR is presented demonstrating that a 2-arylalkylamino substituent in conjunction with suitable 4-diamino substituent are essential for achieving selectivity over many kinases. Additional hit to lead profiling is presented on selected compounds. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.056

文献信息

• 2,4-DIAMINOPYRIMIDINE DERIVATIVES USEFUL AS INHIBITORS OF PKC-THETA
  申请人：Boehringer Ingelheim Pharmaceuticals Inc.

  公开号：EP1590334B1

  公开（公告）日：2009-08-19
• US7550473B2
  申请人：——

  公开号：US7550473B2

  公开（公告）日：2009-06-23
• Discovery of potent and selective PKC-θ inhibitors
  作者：Charles L. Cywin、Georg Dahmann、Anthony S. Prokopowicz、Erick R.R. Young、Ronald L. Magolda、Mario G. Cardozo、Derek A. Cogan、Darren DiSalvo、John D. Ginn、Mohammed A. Kashem、John P. Wolak、Carol A. Homon、Thomas M. Farrell、Heather Grbic、Hanbo Hu、Paul V. Kaplita、Lisa H. Liu、Denice M. Spero、Deborah D. Jeanfavre、Kathy M. O’Shea、Della M. White、Joseph R. Woska、Maryanne L. Brown

  DOI：10.1016/j.bmcl.2006.09.056

  日期：2007.1

  An uHTS campaign was performed to identify selective inhibitors of PKC-theta. Initial triaging of the hit set based on selectivity and historical analysis led to the identification of 2,4-diamino-5-nitropyrimidines as potent and selective PKC-theta inhibitors. A homology model and initial SAR is presented demonstrating that a 2-arylalkylamino substituent in conjunction with suitable 4-diamino substituent are essential for achieving selectivity over many kinases. Additional hit to lead profiling is presented on selected compounds. (c) 2006 Elsevier Ltd. All rights reserved.
• Pyrimidine derivatives useful as inhibitors of PKC-theta
  申请人：Cardozo G. Mario

  公开号：US20050124640A1

  公开（公告）日：2005-06-09

  Disclosed are novel compounds of formula (I): wherein R 1 , R 2 and R 3 are as defined herein, which are useful as inhibitors of PKC-theta and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC-theta, including immunological disorders and type II diabetes. This invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

  揭示了一种新的化合物，其化学式为（I）：其中R1、R2和R3如本文所定义，这些化合物可用作PKC-theta的抑制剂，因此可用于治疗通过PKC-theta活性介导或维持的各种疾病和疾病，包括免疫性疾病和2型糖尿病。本发明还涉及包含这些化合物的药物组合物，使用这些化合物治疗各种疾病和疾病的方法，制备这些化合物的工艺以及在这些工艺中有用的中间体。