(3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluoropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole | 1309960-93-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 硼酸衍生物
• 英文名称: (3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluoropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole
• 英文别名: 1-(3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluoropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole；tert-butyl-[2-fluoro-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]propoxy]-dimethylsilane
• CAS: 1309960-93-7
• 化学式: C₁₈H₃₄BFN₂O₃Si
• 分子量: 384.374
• InChiKey: ASYRDIXKVFZVEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.54
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  45.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N'-(3-dhloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]-pyridin-7-yl)-N,N-dimethylsulfuric diamide 、 (3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluoropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole 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58%的产率得到rac-N'-{3-[1-(2-fluoro-3-hydroxypropyl)-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：

  3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluoropropan-1-ol 在 2,6-二甲基吡啶 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.83h， 生成 (3-{[tert-butyl(dimethyl)silyl]oxy}-2-fluoropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole
  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

• Therapeutic Compounds
  申请人：Katz Jason

  公开号：US20110207711A1

  公开（公告）日：2011-08-25

  The present invention relates to pyrazolopyridines and imidazopyridines which are inhibitors of the kinase PDK1 and are thus useful for the treatment of myeloproliferative disorders or cancer. The compounds are also useful as inhibitors of other kinases such as FGFR3, NTRK3, RP-S6K and WEE1. Furthermore, the present compounds also selectively inhibit microtubule affinity regulating kinase (MARK) and are therefore useful for the treatment or prevention of Alzheimer's disease.

  本发明涉及一种抑制激酶PDK1的吡唑吡啶和咪唑吡啶化合物，因此可用于治疗骨髓增生性疾病或癌症。这些化合物也可用作其他激酶的抑制剂，例如FGFR3、NTRK3、RP-S6K和WEE1。此外，本化合物还具有选择性抑制微管亲和力调节激酶（MARK）的作用，因此可用于治疗或预防阿尔茨海默病。
• Therapeutic compounds
  申请人：Katz Jason

  公开号：US08455477B2

  公开（公告）日：2013-06-04

  The present invention relates to pyrazolopyridines and imidazopyridines which are inhibitors of the kinase PDK1 and are thus useful for the treatment of myeloproliferative disorders or cancer. The compounds are also useful as inhibitors of other kinases such as FGFR3, NTRK3, RP-S6K and WEE1. Furthermore, the present compounds also selectively inhibit microtubule affinity regulating kinase (MARK) and are therefore useful for the treatment or prevention of Alzheimer's disease.

  本发明涉及一种吡唑吡啶和咪唑吡啶，它们是激酶PDK1的抑制剂，因此可用于治疗骨髓增生性疾病或癌症。这些化合物还可用作其他激酶的抑制剂，例如FGFR3、NTRK3、RP-S6K和WEE1。此外，本化合物还能选择性地抑制微管亲和力调节激酶(MARK)，因此可用于治疗或预防阿尔茨海默病。
• 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.