4-(4-methanesulfonyl-piperidin-1-yl)-1-(2-methylsulfanyl-pyrimidin-4-yl)-1H-indazole | 1263480-63-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 4-(4-methanesulfonyl-piperidin-1-yl)-1-(2-methylsulfanyl-pyrimidin-4-yl)-1H-indazole
• 英文别名: 1-(2-methylsulfanylpyrimidin-4-yl)-4-(4-methylsulfonylpiperidin-1-yl)indazole
• CAS: 1263480-63-2
• 化学式: C₁₈H₂₁N₅O₂S₂
• 分子量: 403.529
• InChiKey: WQBDZDBEWKTDLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(4-methanesulfonyl-piperidin-1-yl)-1-(2-methylsulfanyl-pyrimidin-4-yl)-1H-indazole 在 二乙基异丙基胺 、 间氯过氧苯甲酸 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-{4-[4-(4-methanesulfonyl-piperidin-1-yl)-indazol-1-yl]-pyrimidin-2-ylamino}-cyclohexanecarboxylic acid ethyl ester
  参考文献：
  名称：

  Development of indole/indazole-aminopyrimidines as inhibitors of c-Jun N-terminal kinase (JNK): Optimization for JNK potency and physicochemical properties

  摘要：

  A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was used to optimize the series resulting in a significant potency improvement. The best compound (17) has IC50 of 3 nM for JNK1 and 20 nM for JNK2, with greater than 40-fold selectivity against other kinases with good physicochemical and pharmacokinetic properties. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.029
• 作为产物：
  描述：

  2,6-二氟苯甲醛 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 、 乙腈 为溶剂， 反应 1.5h， 生成 4-(4-methanesulfonyl-piperidin-1-yl)-1-(2-methylsulfanyl-pyrimidin-4-yl)-1H-indazole
  参考文献：
  名称：

  Inhibitors of JNK

  摘要：

  该发明涉及JNK抑制剂及相应的用于抑制JNK和治疗JNK介导的疾病的方法、配方和组合物。该申请披露了如下所述的JNK抑制剂，其化学式如下： 其中p、q、Y'、r、R1、R2、X、X1、X2、X3和X4如本文所定义。本文披露的化合物和组合物可用于调节JNK的活性并治疗与JNK活性相关的疾病。本文还披露了用于抑制JNK和治疗JNK介导的疾病等的方法和配方，以及用于制备上述化合物的过程和相应的组合物。

  公开号：

  US20110034470A1

文献信息

• INHIBITORS OF JNK
  申请人：F.Hoffmann-La Roche AG

  公开号：EP2464640A1

  公开（公告）日：2012-06-20
• US8536172B2
  申请人：——

  公开号：US8536172B2

  公开（公告）日：2013-09-17
• [EN] INHIBITORS OF JNK<br/>[FR] INHIBITEURS DE JNK
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011018417A1

  公开（公告）日：2011-02-17

  The invention relates to JNK inhibitors and corresponding methods, formulations, and compositions for inhibiting JNK and treating JNK-mediated disorders. The application discloses JNK inhibitors, as described below in Formula I: wherein p, q, Y', r, R1, R2, X, X1, X2, X3, and X4 are as defined herein. The compounds and compositions disclosed herein are useful to modulate the activity of JNK and treat diseases associated with JNK activity. Disclosed are methods and formulations for inhibiting JNK and treating JNK-mediated disorders, and the like, with the compounds, and processes for making said compounds, and corresponding compositions, disclosed herein.
• Inhibitors of JNK
  申请人：Gong Leyi

  公开号：US20110034470A1

  公开（公告）日：2011-02-10

  The invention relates to JNK inhibitors and corresponding methods, formulations, and compositions for inhibiting JNK and treating JNK-mediated disorders. The application discloses JNK inhibitors, as described below in Formula I: wherein p, q, Y′, r, R 1 , R 2 , X, X 1 , X 2 , X 3 , and X 4 are as defined herein. The compounds and compositions disclosed herein are useful to modulate the activity of JNK and treat diseases associated with JNK activity. Disclosed are methods and formulations for inhibiting JNK and treating JNK-mediated disorders, and the like, with the compounds, and processes for making said compounds, and corresponding compositions, disclosed herein.

  该发明涉及JNK抑制剂及相应的用于抑制JNK和治疗JNK介导的疾病的方法、配方和组合物。该申请披露了如下所述的JNK抑制剂，其化学式如下： 其中p、q、Y'、r、R1、R2、X、X1、X2、X3和X4如本文所定义。本文披露的化合物和组合物可用于调节JNK的活性并治疗与JNK活性相关的疾病。本文还披露了用于抑制JNK和治疗JNK介导的疾病等的方法和配方，以及用于制备上述化合物的过程和相应的组合物。
• Development of indole/indazole-aminopyrimidines as inhibitors of c-Jun N-terminal kinase (JNK): Optimization for JNK potency and physicochemical properties
  作者：Leyi Gong、Xiaochun Han、Tania Silva、Yun-Chou Tan、Bindu Goyal、Parch Tivitmahaisoon、Alejandra Trejo、Wylie Palmer、Heather Hogg、Alam Jahagir、Muzaffar Alam、Paul Wagner、Karin Stein、Lubov Filonova、Brad Loe、Ferenc Makra、David Rotstein、Lubica Rapatova、James Dunn、Fengrong Zuo、Joseph Dal Porto、Brian Wong、Sue Jin、Alice Chang、Patricia Tran、Gary Hsieh、Linghao Niu、Ada Shao、Deborah Reuter、Johaness Hermann、Andreas Kuglstatter、David Goldstein

  DOI：10.1016/j.bmcl.2013.04.029

  日期：2013.6

  A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was used to optimize the series resulting in a significant potency improvement. The best compound (17) has IC50 of 3 nM for JNK1 and 20 nM for JNK2, with greater than 40-fold selectivity against other kinases with good physicochemical and pharmacokinetic properties. (C) 2013 Elsevier Ltd. All rights reserved.