2-chloro-2-(1-(quinolin-6-yl)cyclopropyl)acetaldehyde | 1029715-02-3

• 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: 2-chloro-2-(1-(quinolin-6-yl)cyclopropyl)acetaldehyde
• 英文别名: chloro(1-quinolin-6-ylcyclopropyl)acetaldehyde；Chloro(1-quinolin-6-ylcyclopropyl)acetaldehyde；2-chloro-2-(1-quinolin-6-ylcyclopropyl)acetaldehyde
• CAS: 1029715-02-3
• 化学式: C₁₄H₁₂ClNO
• 分子量: 245.708
• InChiKey: TZAKHFGDILNCSO-UHFFFAOYSA-N

物化性质

• 沸点：
  399.9±17.0 °C(Predicted)
• 密度：
  1.310±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-2-(1-(quinolin-6-yl)cyclopropyl)acetaldehyde 在 lithium hydroxide monohydrate 、 1,1'-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex 、 sodium carbonate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 63.0h， 生成 2-fluoro-4-(8-fluoro-3-(1-(quinolin-6-yl)cyclopropyl)imidazo[1,2-a]pyridin-6-yl)-N-methylbenzamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Imidazo[1,2-a]pyridine Derivatives as Potent c-Met Inhibitors

  摘要：

  A series of imidazo[1,2-a]pyridine derivatives against c-Met was designed by means of bioisosteric replacement. In this study, a selective, potent c-Met inhibitor, 22e was identified, with IC50 values of 3.9 nM against c-Met kinase and 45.0 nM against c-Met-addicted EBC-1 cell proliferation, respectively. Compound 22e inhibited c-Met phosphorylation and downstream signaling across different oncogenic forms in c-Met overactivated cancer cells and model cells. Compound 22e significantly inhibited tumor growth (TGI = 75%) with good oral bioavailability (F = 29%) and no significant hERG inhibition. On the basis of systematic metabolic study, the pathway of all possible metabolites of 22e in liver microsomes of different species has been proposed, and a major NADPH-dependent metabolite 33 was generated by liver microsomes. To block the metabolic site, 42 was designed and synthesized for further evaluation. Taken together, the imidazo[1,2-a]pyridine scaffold showed promising pharmacological inhibition of c-Met and warrants further investigation.

  DOI：

  10.1021/ml5004876
• 作为产物：
  描述：

  2-(喹啉-6-基)乙腈 在 N-氯代丁二酰亚胺 、 potassium tert-butylate 、 苄基三乙基氯化铵 、 二异丁基氢化铝 、 D-脯氨酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 13.0h， 生成 2-chloro-2-(1-(quinolin-6-yl)cyclopropyl)acetaldehyde
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Imidazo[1,2-a]pyridine Derivatives as Potent c-Met Inhibitors

  摘要：

  A series of imidazo[1,2-a]pyridine derivatives against c-Met was designed by means of bioisosteric replacement. In this study, a selective, potent c-Met inhibitor, 22e was identified, with IC50 values of 3.9 nM against c-Met kinase and 45.0 nM against c-Met-addicted EBC-1 cell proliferation, respectively. Compound 22e inhibited c-Met phosphorylation and downstream signaling across different oncogenic forms in c-Met overactivated cancer cells and model cells. Compound 22e significantly inhibited tumor growth (TGI = 75%) with good oral bioavailability (F = 29%) and no significant hERG inhibition. On the basis of systematic metabolic study, the pathway of all possible metabolites of 22e in liver microsomes of different species has been proposed, and a major NADPH-dependent metabolite 33 was generated by liver microsomes. To block the metabolic site, 42 was designed and synthesized for further evaluation. Taken together, the imidazo[1,2-a]pyridine scaffold showed promising pharmacological inhibition of c-Met and warrants further investigation.

  DOI：

  10.1021/ml5004876

文献信息

• IMIDAZOTRIAZINES AND IMIDAZOPYRIMIDINES AS KINASE INHIBITORS
  申请人：Incyte Holdings Corporation

  公开号：US20160326178A1

  公开（公告）日：2016-11-10

  The present invention is directed to imidazo[1,2-b][1,2,4]triazines and imidazo[1,2-a]pyrimidines, and pharmaceutical compositions thereof, which are inhibitors of kinases such as c-Met and are useful in the treatment of cancer and other diseases related to the dysregulation of kinase pathways.

  本发明涉及咪唑[1,2-b][1,2,4]三嗪和咪唑[1,2-a]嘧啶，以及其制成的药物组合物，该组合物是c-Met激酶抑制剂，可用于治疗癌症和与激酶通路失调有关的其他疾病。
• Imidazotriazines and imidazopyrimidines as kinase inhibitors
  申请人：Incyte Corporation

  公开号：US07767675B2

  公开（公告）日：2010-08-03

  The present invention is directed to imidazo[1,2-b][1,2,4]triazines and imidazo[1,2-a]pyrimidines, and pharmaceutical compositions thereof, which are inhibitors of kinases such as c-Met and are useful in the treatment of cancer and other diseases related to the dysregulation of kinase pathways.

  本发明涉及咪唑并[1,2-b][1,2,4]三嗪和咪唑并[1,2-a]嘧啶，以及它们的药物组合物，它们是c-Met激酶抑制剂，可用于治疗与激酶通路失调相关的癌症和其他疾病。
• Imidazotriaines and imidazopyrimidines as kinase inhibitors
  申请人：Incyte Corporation

  公开号：US10738052B2

  公开（公告）日：2020-08-11

  The present invention is directed to imidazo[1,2-b][1,2,4]triazines and imidazo[1,2-a]pyrimidines, and pharmaceutical compositions thereof, which are inhibitors of kinases such as c-Met and are useful in the treatment of cancer and other diseases related to the dysregulation of kinase pathways.

  本发明涉及咪唑并[1,2-b][1,2,4]三嗪和咪唑并[1,2-a]嘧啶及其药物组合物，它们是激酶（如 c-Met）的抑制剂，可用于治疗癌症和其他与激酶通路失调有关的疾病。
• WO2008/64157
  申请人：——

  公开号：——

  公开（公告）日：——
• Imidazotriaines and Imidazopyrimidines as Kinase Inhibitors
  申请人：Incyte Corporation

  公开号：US20180282340A1

  公开（公告）日：2018-10-04

  The present invention is directed to imidazo[1,2-b][1,2,4]triazines and imidazo[1,2-a]pyrimidines, and pharmaceutical compositions thereof, which are inhibitors of kinases such as c-Met and are useful in the treatment of cancer and other diseases related to the dysregulation of kinase pathways.