6-chloro-N4-(cyclohexylmethyl)-2,4-pyrimidinediamine | 122862-58-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-chloro-N4-(cyclohexylmethyl)-2,4-pyrimidinediamine
• 英文别名: 6-chloro-4-N-(cyclohexylmethyl)pyrimidine-2,4-diamine
• CAS: 122862-58-2
• 化学式: C₁₁H₁₇ClN₄
• 分子量: 240.736
• InChiKey: UXRFJEYDPFKPTC-UHFFFAOYSA-N

物化性质

• 熔点：
  114-115 °C(Solv: dichloromethane (75-09-2))
• 沸点：
  466.7±48.0 °C(Predicted)
• 密度：
  1.253±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  63.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-N4-(cyclohexylmethyl)-2,4-pyrimidinediamine 在 sodium hydroxide 、 sodium acetate 作用下， 以 水 、 乙二醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 9-(cyclohexylmethyl)-7-deazaguanine
  参考文献：
  名称：

  Higher Affinity Quadruply Hydrogen-Bonded Complexation with 7-Deazaguanine Urea

  摘要：

  UG forms a highly stable quadruply hydrogen-bonded heterocomplex with DAN, but the fidelity of the complex is lowered somewhat by the Hoogsteen-side oligornerization of UG (K-assoc similar to 230 M-1, CDCl3). DeUG was prepared as a more robust analogue of UG lacking the Hoogsteen nitrogen atom. Remarkably, the deaza analogue, DeUG, forms a much more stable complex with DAN (> 10-fold higher K-assoc for DeUG.DAN vs UG.DAN) but also dimerizes more strongly (K-dim = 880 +/- 40 M-1, CDCl3) by adopting a conformation preorganized for both binding and dimerization.

  DOI：

  10.1021/ol0601803
• 作为产物：
  描述：

  2-氨基-4,6-二氯嘧啶 、 环己甲胺 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以66%的产率得到6-chloro-N4-(cyclohexylmethyl)-2,4-pyrimidinediamine
  参考文献：
  名称：

  [EN] CHEMICAL COMPOUNDS
  [FR] COMPOSÉS CHIMIQUES

  摘要：

  这项发明涉及6-(4-吡咯嗪基)-1 H-吲唑衍生物。具体而言，该发明涉及符合式(I)的化合物，其中R1-R4在此处被定义。该发明的化合物是PDK1的抑制剂，可用于治疗由于恒定激活的ACG激酶所特征化的免疫和代谢性疾病和紊乱，如癌症，更具体地说是乳腺癌、结肠癌和肺癌。因此，该发明进一步涉及包括该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包括该发明化合物的药物组合物来抑制PDK1活性和治疗相关疾病的方法。

  公开号：

  WO2010059658A1

文献信息

• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2010059658A1

  公开（公告）日：2010-05-27

  The invention is directed to 6-(4-pyιϊmidinyl)-1 H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1 - R4 are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  这项发明涉及6-(4-吡咯嗪基)-1 H-吲唑衍生物。具体而言，该发明涉及符合式(I)的化合物，其中R1-R4在此处被定义。该发明的化合物是PDK1的抑制剂，可用于治疗由于恒定激活的ACG激酶所特征化的免疫和代谢性疾病和紊乱，如癌症，更具体地说是乳腺癌、结肠癌和肺癌。因此，该发明进一步涉及包括该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包括该发明化合物的药物组合物来抑制PDK1活性和治疗相关疾病的方法。
• CHEMICAL COMPOUNDS
  申请人：Axten Jeffrey Michael

  公开号：US20110275611A1

  公开（公告）日：2011-11-10

  The invention is directed to 6-(4-pyrimidinyl)-1H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R 1 -R 4 are defined herein. The compounds of the invention axe inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention

  本发明涉及6-(4-嘧啶基)-1H-吲唑衍生物。具体而言，本发明涉及公式（I）中R1-R4所定义的化合物。本发明的化合物是PDK1的抑制剂，可用于治疗免疫和代谢性疾病和障碍，这些疾病和障碍以恒定激活的ACG激酶为特征，例如乳腺、结肠和肺癌等。因此，本发明还涉及包含本发明化合物的制药组合物。本发明还涉及使用本发明化合物或包含本发明化合物的制药组合物抑制PDK1活性和治疗相关障碍的方法。
• Chemical compounds
  申请人：Axten Jeffrey Michael

  公开号：US08697685B2

  公开（公告）日：2014-04-15

  The invention is directed to 6-(4-pyrimidinyl)-1H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1-R4 are defined herein. The compounds of the invention axe inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及6-(4-嘧啶基)-1H-吲唑衍生物。具体而言，本发明涉及公式(I)中R1-R4所定义的化合物。本发明的化合物是PDK1的抑制剂，可用于治疗免疫和代谢性疾病和障碍，这些疾病和障碍以恒定激活的ACG激酶为特征，例如乳腺癌、结肠癌和肺癌等癌症。因此，本发明进一步涉及包括本发明化合物的药物组合物。本发明还涉及使用本发明化合物或包括本发明化合物的药物组合物来抑制PDK1活性和治疗与之相关的疾病的方法。
• Higher Affinity Quadruply Hydrogen-Bonded Complexation with 7-Deazaguanine Urea
  作者：Hugo C. Ong、Steven C. Zimmerman

  DOI：10.1021/ol0601803

  日期：2006.4.1

  UG forms a highly stable quadruply hydrogen-bonded heterocomplex with DAN, but the fidelity of the complex is lowered somewhat by the Hoogsteen-side oligornerization of UG (K-assoc similar to 230 M-1, CDCl3). DeUG was prepared as a more robust analogue of UG lacking the Hoogsteen nitrogen atom. Remarkably, the deaza analogue, DeUG, forms a much more stable complex with DAN (> 10-fold higher K-assoc for DeUG.DAN vs UG.DAN) but also dimerizes more strongly (K-dim = 880 +/- 40 M-1, CDCl3) by adopting a conformation preorganized for both binding and dimerization.