4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde oxime | 1425933-26-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde oxime
• 英文别名: N-[[4-fluoro-1-(oxan-2-yl)benzimidazol-5-yl]methylidene]hydroxylamine
• CAS: 1425933-26-1
• 化学式: C₁₃H₁₄FN₃O₂
• 分子量: 263.271
• InChiKey: KUPDUGXGBMVZJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  59.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde oxime 在 甲酸铵 、 锌 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以47%的产率得到(4-fluoro-1-tetrahydropyran-2-yl-benzimidazol-5-yl)methanamine
  参考文献：
  名称：

  Structure-Guided Design of Group I Selective p21-Activated Kinase Inhibitors

  摘要：

  The p21-activated kinases (PAKs) play important roles in cytoskeletal organization, cellular morphogenesis, and survival and have generated significant attention as potential therapeutic targets for cancer. Following a high-throughput screen, we identified an aminopyrazole scaffold-based series that was optimized to yield group I selective PAK inhibitors. A structure-based design effort aimed at targeting the ribose pocket for both potency and selectivity led to much-improved group I vs II selectivity. Early lead compounds contained a basic primary amine, which was found to be a major metabolic soft spot with in vivo clearance proceeding predominantly via N-acetylation. We succeeded in identifying replacements with improved metabolic stability, leading to compounds with lower in vivo rodent clearance and excellent group I PAK selectivity.

  DOI：

  10.1021/acs.jmedchem.5b00572
• 作为产物：
  描述：

  5-bromo-4-fluoro-1H-benzo[d]imidazole 在 正丁基锂 、 盐酸羟胺 、 sodium acetate 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 17.75h， 生成 4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde oxime
  参考文献：
  名称：

  [EN] SERINE/THREONINE PAK1 INHIBITORS
  [FR] INHIBITEURS DE SÉRINE/THRÉONINE PAK1

  摘要：

  具有以下式I的化合物，其中A、Z、R1a、R1b、R2、R3、R4、R5、R6、R7、R9、R10、Ra、Rb和n的定义如本文所述，是PAK1的抑制剂。还公开了用于治疗癌症和高增殖性疾病的组合物和方法。

  公开号：

  WO2013026914A1

文献信息

• [EN] SERINE/THREONINE PAK1 INHIBITORS<br/>[FR] INHIBITEURS DE SÉRINE/THRÉONINE PAK1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013026914A1

  公开（公告）日：2013-02-28

  Compounds having the formula I wherein A, Z, R1a, R1b, R2, R3, R4, R5, R6, R7, R9, R10, Ra, Rb and n are as defined herein are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.

  具有以下式I的化合物，其中A、Z、R1a、R1b、R2、R3、R4、R5、R6、R7、R9、R10、Ra、Rb和n的定义如本文所述，是PAK1的抑制剂。还公开了用于治疗癌症和高增殖性疾病的组合物和方法。
• SERINE/THREONINE KINASE INHIBITORS
  申请人：Aliagas-Martin Ignacio

  公开号：US20130225620A1

  公开（公告）日：2013-08-29

  Compounds having the formula I wherein A, Z, R 1a , R 1b , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , R a , R b and n are as defined herein are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.

  具有公式I的化合物，其中A，Z，R1a，R1b，R2，R3，R4，R5，R6，R7，R9，R10，Ra，Rb和n的定义如本文所述，是PAK1的抑制剂。还公开了治疗癌症和高增殖性疾病的组合物和方法。
• Serine/threonine kinase inhibitors
  申请人：Aliagas-Martin Ignacio

  公开号：US08637537B2

  公开（公告）日：2014-01-28

  Compounds having the formula I wherein A, Z, R1a, R1b, R2, R3, R4, R5, R6, R7, R9, R10, Ra, Rb and n are as defined herein are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.

  具有式I的化合物，其中A，Z，R1a，R1b，R2，R3，R4，R5，R6，R7，R9，R10，Ra，Rb和n如本文所定义，是PAK1的抑制剂。还公开了用于治疗癌症和增殖性疾病的组合物和方法。
• Structure-Guided Design of Group I Selective p21-Activated Kinase Inhibitors
  作者：James J. Crawford、Wendy Lee、Ignacio Aliagas、Simon Mathieu、Klaus P. Hoeflich、Wei Zhou、Weiru Wang、Lionel Rouge、Lesley Murray、Hank La、Ning Liu、Peter W. Fan、Jonathan Cheong、Christopher E. Heise、Sreemathy Ramaswamy、Robert Mintzer、Yanzhou Liu、Qi Chao、Joachim Rudolph

  DOI：10.1021/acs.jmedchem.5b00572

  日期：2015.6.25

  The p21-activated kinases (PAKs) play important roles in cytoskeletal organization, cellular morphogenesis, and survival and have generated significant attention as potential therapeutic targets for cancer. Following a high-throughput screen, we identified an aminopyrazole scaffold-based series that was optimized to yield group I selective PAK inhibitors. A structure-based design effort aimed at targeting the ribose pocket for both potency and selectivity led to much-improved group I vs II selectivity. Early lead compounds contained a basic primary amine, which was found to be a major metabolic soft spot with in vivo clearance proceeding predominantly via N-acetylation. We succeeded in identifying replacements with improved metabolic stability, leading to compounds with lower in vivo rodent clearance and excellent group I PAK selectivity.