4-(4-Methylsulfonylpiperazin-1-yl)-1-(2-methylsulfonylpyrimidin-4-yl)indole | 1438899-25-2

• 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: 4-(4-Methylsulfonylpiperazin-1-yl)-1-(2-methylsulfonylpyrimidin-4-yl)indole
• 英文别名: 4-(4-methylsulfonylpiperazin-1-yl)-1-(2-methylsulfonylpyrimidin-4-yl)indole
• CAS: 1438899-25-2
• 化学式: C₁₈H₂₁N₅O₄S₂
• 分子量: 435.528
• InChiKey: OXZINGGWCBKKHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  122
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-((1R,4R)-4-aminocyclohexyl)methanesulfonamide 、 4-(4-Methylsulfonylpiperazin-1-yl)-1-(2-methylsulfonylpyrimidin-4-yl)indole 在 二乙基异丙基胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成 N-(4-{4-[4-(4-methanesulfonyl-piperazin-1-yl)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanesulfonamide
  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：

  4-溴吲哚 在 bis(tri-tert-butylphosphine)palladium(0) 、 sodium hydride 、 间氯过氧苯甲酸 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 4-(4-Methylsulfonylpiperazin-1-yl)-1-(2-methylsulfonylpyrimidin-4-yl)indole
  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

文献信息

• 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.