N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide | 1239461-60-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide
• 英文别名: N-[4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl]-2-(2-oxo-3,4-dihydroquinolin-1-yl)acetamide
• CAS: 1239461-60-9
• 化学式: C₁₇H₁₄BrN₅O₂S
• 分子量: 432.3
• InChiKey: JCKBTQZTGPJTII-UHFFFAOYSA-N

物化性质

• 密度：
  1.675±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基噻吩-3-甲腈 在 吡啶 、 硫酸 、 溴 、 sodium acetate 、 溶剂黄146 、 肼 、 N-甲基乙二胺 、 锌 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 水 、 溶剂黄146 为溶剂， 反应 1.25h， 生成 N-(4-bromo-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl)-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide
  参考文献：
  名称：

  Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration

  摘要：

  The SAR of a series of brain penetrant, trisubstituted thiophene based JNK inhibitors with improved pharmacokinetic properties is described. These compounds were designed based on information derived from metabolite identification studies which led to compounds such as 42 with lower clearance, greater brain exposure and longer half life compared to earlier analogs. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.100

文献信息

• [EN] INHIBITORS OF JUN N-TERMINAL KINASE<br/>[FR] INHIBITEURS DE L'ENZYME JUN N-TERMINAL KINASE
  申请人：ELAN PHARM INC

  公开号：WO2010091310A1

  公开（公告）日：2010-08-12

  The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula (I): or a salt or solvate thereof, wherein ring A, Ca, Cb, Z, R5, W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

  本公开提供了具有以下结构的c-Jun N-末端激酶（JNK）抑制剂（I）的结构，或其盐或溶剂化物，其中环A，Ca，Cb，Z，R5，W和Cy在此处定义。本公开还提供了包括本公开化合物的药物组合物，以及制备和使用本公开化合物和组合物的方法，例如在治疗和预防各种疾病，如阿尔茨海默病。
• INHIBITORS OF JUN N-TERMINAL KINASE
  申请人：SHAM Hing L.

  公开号：US20130072494A1

  公开（公告）日：2013-03-21

  The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula: or a salt or solvate thereof, wherein ring A, C a , C b , Z, R 5 , W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

  本公开提供了具有以下结构的c-Jun N端激酶（JNK）抑制剂： 或其盐或溶剂，其中环A、Ca、Cb、Z、R5、W和Cy在此被定义。本公开还提供了包括本公开化合物的药物组合物以及制备和使用本公开化合物和组合物的方法，例如，在治疗和预防各种疾病，如阿尔茨海默病中使用。
• Inhibitors of Jun N-Terminal Kinase
  申请人：Sham Hing L.

  公开号：US20100331335A1

  公开（公告）日：2010-12-30

  The present disclosure provides inhibitors of c-Jun N-terminal kinases (JNK) having a structure according to the following formula: or a salt or solvate thereof, wherein ring A, C a , C b , Z, R 5 , W and Cy are defined herein. The disclosure further provides pharmaceutical compositions including the compounds of the present disclosure and methods of making and using the compounds and compositions of the present disclosure, e.g., in the treatment and prevention of various disorders, such as Alzheimer's disease.

  本公开提供抑制c-Jun N-末端激酶（JNK）的抑制剂，其结构符合以下公式：其中环A、Ca、Cb、Z、R5、W和Cy在此定义。本公开还提供包括本公开化合物的药物组合物以及制备和使用本公开化合物和组合物的方法，例如在治疗和预防各种疾病，如阿尔茨海默病中的应用。
• Design and synthesis of a novel, orally active, brain penetrant, tri-substituted thiophene based JNK inhibitor
  作者：Simeon Bowers、Anh P. Truong、R. Jeffrey Neitz、Martin Neitzel、Gary D. Probst、Roy K. Hom、Brian Peterson、Robert A. Galemmo、Andrei W. Konradi、Hing L. Sham、Gergley Tóth、Hu Pan、Nanhua Yao、Dean R. Artis、Elizabeth F. Brigham、Kevin P. Quinn、John-Michael Sauer、Kyle Powell、Lany Ruslim、Zhao Ren、Frédérique Bard、Ted A. Yednock、Irene Griswold-Prenner

  DOI：10.1016/j.bmcl.2011.01.046

  日期：2011.3

  The SAR of a series of tri-substituted thiophene JNK3 inhibitors is described. By optimizing both the N-aryl acetamide region of the inhibitor and the 4-position of the thiophene we obtained single digit nanomolar compounds, such as 47, which demonstrated an in vivo effect on JNK activity when dosed orally in our kainic acid mouse model as measured by phospho-c-jun reduction.
• TREATMENT OF FIBROTIC DISORDERS WITH JUN N-TERMINAL KINASE INHIBITORS
  申请人：Imago Pharmaceuticals, Inc.

  公开号：EP3509586A1

  公开（公告）日：2019-07-17