4-(4-bromo-1H-pyrazol-1-yl)-1-ethylpiperidine | 1309961-03-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(4-bromo-1H-pyrazol-1-yl)-1-ethylpiperidine
• 英文别名: 4-(4-bromopyrazol-1-yl)-1-ethylpiperidine
• CAS: 1309961-03-2
• 化学式: C₁₀H₁₆BrN₃
• 分子量: 258.161
• InChiKey: HDEYSXPLFLUGLU-UHFFFAOYSA-N

物化性质

• 沸点：
  330.5±32.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  21.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(4-bromo-1H-pyrazol-1-yl)-1-ethylpiperidine 、 N,N-dimethyl-N'-[5-oxo-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]sulfuric diamide 在 potassium fluoride 、 tris-(dibenzylideneacetone)dipalladium(0) 、 tri tert-butylphosphoniumtetrafluoroborate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以30%的产率得到N'-{3-[1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl]-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl}-N,N-dimethylsulfuric diamide
  参考文献：
  名称：

  Discovery of a 5H-Benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (MK-2461) Inhibitor of c-Met Kinase for the Treatment of Cancer

  摘要：

  c-Met is a transmembrane tyrosine kinase that mediates activation of several signaling pathways implicated in aggressive cancer phenotypes. In recent years, research into this area has highlighted c-Met as an attractive cancer drug target, triggering a number of approaches to disrupt aberrant c-Met signaling. Screening efforts identified a unique class of 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one kinase inhibitors, exemplified by 1. Subsequent SAR studies led to the development of 81 (MK-2461), a potent inhibitor of c-Met that was efficacious in preclinical animal models of tumor suppression. In addition, biochemical studies and X-ray analysis have revealed that this unique class of kinase inhibitors binds preferentially to the activated (phosphorylated) form of the kinase. This report details the development of 81 and provides a description of its unique biochemical properties.

  DOI：

  10.1021/jm200112k
• 作为产物：
  描述：

  4-(4-溴吡唑-1-基)哌啶-1-甲酸叔丁酯 在 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 4-(4-bromo-1H-pyrazol-1-yl)-1-ethylpiperidine
  参考文献：
  名称：

  Discovery of a 5H-Benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (MK-2461) Inhibitor of c-Met Kinase for the Treatment of Cancer

  摘要：

  c-Met is a transmembrane tyrosine kinase that mediates activation of several signaling pathways implicated in aggressive cancer phenotypes. In recent years, research into this area has highlighted c-Met as an attractive cancer drug target, triggering a number of approaches to disrupt aberrant c-Met signaling. Screening efforts identified a unique class of 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one kinase inhibitors, exemplified by 1. Subsequent SAR studies led to the development of 81 (MK-2461), a potent inhibitor of c-Met that was efficacious in preclinical animal models of tumor suppression. In addition, biochemical studies and X-ray analysis have revealed that this unique class of kinase inhibitors binds preferentially to the activated (phosphorylated) form of the kinase. This report details the development of 81 and provides a description of its unique biochemical properties.

  DOI：

  10.1021/jm200112k

文献信息

• [EN] PYRAZOLE-SUBSTITUTED AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS<br/>[FR] COMPOSES AMINOHETEROARYLE A SUBSTITUTION PYRAZOLE SERVANT D'INHIBITEURS DE PROTEINE KINASE
  申请人：PFIZER

  公开号：WO2006021881A2

  公开（公告）日：2006-03-02

  Compounds of formula (1) are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了化学式（1）的化合物，以及它们的合成和使用方法。优选的化合物是c-Met蛋白激酶的有效抑制剂，并可用于治疗异常细胞生长障碍，如癌症。
• Pyrazole-substituted aminoheteroaryl compounds as protein kinase inhibitors
  申请人：Cui Jean Jingrong

  公开号：US20060128724A1

  公开（公告）日：2006-06-15

  Compounds of formula 1 are provided, as well as methods for their synthesis and use. Preferred compounds are potent inhibitors of the c-Met protein kinase, and are useful in the treatment of abnormal cell growth disorders, such as cancers.

  提供了化学式1的化合物，以及它们的合成和使用方法。首选的化合物是c-Met蛋白激酶的强效抑制剂，并且在治疗异常细胞生长障碍，例如癌症方面非常有用。
• PYRAZOLE-SUBSTITUTED AMINOHETEROARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS
  申请人：Pfizer Inc.

  公开号：EP1784396B8

  公开（公告）日：2011-04-20
• HPK1 INHIBITORS, PREPARATION METHOD AND APPLICATION THEREOF
  申请人：Zhuhai Yufan Biotechnologies Co., Ltd

  公开号：EP3781563B1

  公开（公告）日：2022-06-29
• Discovery of a 5<i>H</i>-Benzo[4,5]cyclohepta[1,2-<i>b</i>]pyridin-5-one (MK-2461) Inhibitor of c-Met Kinase for the Treatment of Cancer
  作者：Jason D. Katz、James P. Jewell、David J. Guerin、Jongwon Lim、Christopher J. Dinsmore、Sujal V. Deshmukh、Bo-Sheng Pan、C. Gary Marshall、Wei Lu、Michael D. Altman、William K. Dahlberg、Lenora Davis、Danielle Falcone、Ana E. Gabarda、Gaozhen Hang、Harold Hatch、Rachael Holmes、Kaiko Kunii、Kevin J. Lumb、Bart Lutterbach、Robert Mathvink、Naim Nazef、Sangita B. Patel、Xianlu Qu、John F. Reilly、Keith W. Rickert、Craig Rosenstein、Stephen M. Soisson、Kerrie B. Spencer、Alexander A. Szewczak、Deborah Walker、Wenxian Wang、Jonathan Young、Qinwen Zeng

  DOI：10.1021/jm200112k

  日期：2011.6.23

  c-Met is a transmembrane tyrosine kinase that mediates activation of several signaling pathways implicated in aggressive cancer phenotypes. In recent years, research into this area has highlighted c-Met as an attractive cancer drug target, triggering a number of approaches to disrupt aberrant c-Met signaling. Screening efforts identified a unique class of 5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one kinase inhibitors, exemplified by 1. Subsequent SAR studies led to the development of 81 (MK-2461), a potent inhibitor of c-Met that was efficacious in preclinical animal models of tumor suppression. In addition, biochemical studies and X-ray analysis have revealed that this unique class of kinase inhibitors binds preferentially to the activated (phosphorylated) form of the kinase. This report details the development of 81 and provides a description of its unique biochemical properties.