(3S,6R)-3-(BOC-氨基)-6-甲基哌啶 | 1271024-76-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: (3S,6R)-3-(BOC-氨基)-6-甲基哌啶
• 中文别名: 叔-丁基N-[(3S,6R)-6-甲基哌啶-3-基]氨基甲酯；N-[(3S,6R)-6-甲基哌啶-3-基]氨基甲酸叔丁酯
• 英文名称: 1,1-dimethylethyl [(3S,6R)-6-methyl-3-piperidinyl]carbamate
• 英文别名: tert-Butyl N-[(3S,6R)-6-methylpiperidin-3-yl]carbamate
• CAS: 1271024-76-0
• 化学式: C₁₁H₂₂N₂O₂
• 分子量: 214.308
• InChiKey: NNMBHCRWGGSRBE-BDAKNGLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S,6R)-3-(BOC-氨基)-6-甲基哌啶 在 四(三苯基膦)钯 、 碳酸氢钠 、 一水合肼 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 为溶剂， 生成 1,1-dimethylethyl {(3S,6R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-3-piperidinyl}carbamate
  参考文献：
  名称：

  Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors

  摘要：

  Phosphoinositide-dependent protein kinase-1 (PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDKI might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDKI inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OC1-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDKI and the potential pharmacological uses of a PDK1 inhibitor.

  DOI：

  10.1021/jm101527u

文献信息

• 신규한 PIM 키나아제 억제 화합물 및 이의 용도
  申请人：제일약품주식회사

  公开号：KR20230154382A

  公开（公告）日：2023-11-08

  본 발명은 신규한 PIM 키나아제 억제제 및 이의 용도에 관한 것으로, 보다 상세하게는 PIM 키나아제 억제 활성을 가지는 신규한 화합물 및 이를 포함하는 PIM 키나아제 활성과 관련된 질환의 예방, 개선 또는 치료용 조성물에 관한 것이다. 본 발명의 화합물은 심장독성이 낮으면서도, 효과적으로 PIM 키나아제 억제 활성을 가지는 것을 확인하였으므로, 본 발명의 화합물은 PIM 키나아제 활성과 관련된 암, 자가면역질환, 골수 증식성 장애 또는 죽상동맥경화증과 같은 다양한 질환의 예방, 개선 또는 치료용 조성물로 유용하게 사용될 수 있다.

  本发明涉及新型PIM激酶抑制剂及其用途，更具体地说，涉及具有PIM激酶抑制活性的新型化合物和包含这些化合物的预防、改善或治疗与PIM激酶活性相关疾病的组合物。由于已发现本发明化合物具有有效的 PIM 激酶抑制活性，且心脏毒性低，因此本发明化合物可用于预防、改善或治疗与 PIM 激酶活性相关的各种疾病（如癌症、自身免疫性疾病、骨髓增生性疾病或动脉粥样硬化）的组合物中。
• Structure-Based Design of Potent and Selective 3-Phosphoinositide-Dependent Kinase-1 (PDK1) Inhibitors
  作者：Jesús R. Medina、Christopher J. Becker、Charles W. Blackledge、Celine Duquenne、Yanhong Feng、Seth W. Grant、Dirk Heerding、William H. Li、William H. Miller、Stuart P. Romeril、Daryl Scherzer、Arthur Shu、Mark A. Bobko、Antony R. Chadderton、Melissa Dumble、Christine M. Gardiner、Seth Gilbert、Qi Liu、Sridhar K. Rabindran、Valery Sudakin、Hong Xiang、Pat G. Brady、Nino Campobasso、Paris Ward、Jeffrey M. Axten

  DOI：10.1021/jm101527u

  日期：2011.3.24

  Phosphoinositide-dependent protein kinase-1 (PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDKI might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDKI inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OC1-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDKI and the potential pharmacological uses of a PDK1 inhibitor.