6-chloro-4-N-cyclopentylpyrimidine-2,4-diamine | 1030739-38-8

• 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-4-N-cyclopentylpyrimidine-2,4-diamine
• 英文别名: 6-chloro-N4-cyclopentyl-2,4-pyrimidinediamine；6-chloro-N4-cyclopentylpyrimidine-2,4-diamine
• CAS: 1030739-38-8
• 化学式: C₉H₁₃ClN₄
• mdl: MFCD10598062
• 分子量: 212.682
• InChiKey: NSMGKMXRXZAMDS-UHFFFAOYSA-N

物化性质

• 沸点：
  452.5±48.0 °C(Predicted)
• 密度：
  1.378±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 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-4-N-cyclopentylpyrimidine-2,4-diamine 在 四(三苯基膦)钯 、 碳酸氢钠 、 一水合肼 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 6.0h， 生成 6-(3-amino-1H-indazol-6-yl)-N4-cyclopentyl-2,4-pyrimidinediamine
  参考文献：
  名称：

  Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors

  摘要：

  Phosphoinositide-dependent protein kinase-1 (PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDKI might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDKI inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OC1-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDKI and the potential pharmacological uses of a PDK1 inhibitor.

  DOI：

  10.1021/jm101527u
• 作为产物：
  描述：

  2-氨基-4,6-二氯嘧啶 、 环戊胺 在 氩 、 乙酸乙酯 、 水 、 magnesium sulfate 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以to afford the title compound (605 mg, 93%) as an orange oil的产率得到6-chloro-4-N-cyclopentylpyrimidine-2,4-diamine
  参考文献：
  名称：

  Chemical compounds

  摘要：

  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。

  公开号：

  US08697685B2

文献信息

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

  公开号：WO2010120854A1

  公开（公告）日：2010-10-21

  The invention is directed to to substituted indazole derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1 - R6 and X are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically leukemia and 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.

  本发明涉及取代吲唑衍生物。具体而言，本发明涉及根据公式I的化合物：其中R1-R6和X在此定义。本发明的化合物是PDK1的抑制剂，可用于治疗由组成性激活的ACG激酶（如癌症，特别是白血病、乳腺癌、结肠癌和肺癌）引起的疾病。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本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。
• [EN] MTH1 INHIBITORS FOR TREATMENT OF INFLAMMATORY AND AUTOIMMUNE CONDITIONS<br/>[FR] INHIBITEURS DE MTH1 DESTINÉS AU TRAITEMENT DES ÉTATS INFLAMMATOIRES ET AUTO-IMMUNS
  申请人：THOMAS HELLEDAYS STIFTELSE FÖR MEDICINSK FORSKNING

  公开号：WO2015187089A1

  公开（公告）日：2015-12-10

  A compound of formula (I), or a pharmaceutically acceptable salt thereof, for use in the treatment of autoimmune diseases and inflammatory conditions.

  化合物的化学式（I），或其药学上可接受的盐，用于治疗自身免疫性疾病和炎症性疾病。
• [EN] PYRIMIDINE-2,4-DIAMINE DERIVATIVES FOR TREATMENT OF CANCER<br/>[FR] DÉRIVÉS DE PYRIMIDINE-2,4-DIAMINE UTILISABLES EN VUE DU TRAITEMENT DU CANCER
  申请人：THOMAS HELLEDAYS STIFTELSE FÖR MEDICINSK FORSKNING

  公开号：WO2014084778A1

  公开（公告）日：2014-06-05

  A compound of formula (I), or a pharmaceutically-acceptable salt thereof. The compound is useful in the treatment of cancer or other diseases that may benefit from inhibition of MTH1.

  公式(I)的化合物，或其药用可接受的盐。该化合物可用于治疗癌症或其他可能从抑制MTH1中受益的疾病。
• 6-Chloro-2,4-diaminopyrimidines
  申请人：Sandoz Ltd.

  公开号：US04025515A1

  公开（公告）日：1977-05-24

  The invention concerns pyrimidine derivatives of the formula: ##STR1## in which X is hydrogen or chlorine and R is alkyl or cycloalkyl, in free base or agriculturally acceptable acid addition salt form. The compounds possess herbicidal activity.

  本发明涉及以下式的嘧啶衍生物： ##STR1## 其中X为氢或氯，R为烷基或环烷基，以自由碱或农业上可接受的酸盐形式存在。这些化合物具有除草活性。
• 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。