N-[(3R,6S)-6-甲基哌啶-3-基]氨基甲酸叔丁酯 | 1227917-63-6

• 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: N-[(3R,6S)-6-甲基哌啶-3-基]氨基甲酸叔丁酯
• 英文名称: tert-butyl ((3R,6S)-6-methylpiperidin-3-yl)carbamate
• 英文别名: tert-butyl N-[(3R,6S)-6-methylpiperidin-3-yl]carbamate
• CAS: 1227917-63-6
• 化学式: C₁₁H₂₂N₂O₂
• 分子量: 214.308
• InChiKey: NNMBHCRWGGSRBE-DTWKUNHWSA-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：

  N-[(3R,6S)-6-甲基哌啶-3-基]氨基甲酸叔丁酯 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 {(3R,6S)-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
• 作为产物：
  描述：

  6-甲基烟酸甲酯 在 盐酸 、 platinum(IV) oxide 、 lithium hydroxide monohydrate 、 叠氮磷酸二苯酯 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氧化碳 、 水 、 乙酸乙酯 、 异丙醇 、 叔丁醇 为溶剂， 15.0~100.0 ℃ 、413.7 kPa 条件下， 反应 28.5h， 生成 N-[(3R,6S)-6-甲基哌啶-3-基]氨基甲酸叔丁酯
  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

• [EN] BICYCLIC INHIBITORS OF PAD4<br/>[FR] INHIBITEURS BICYCLIQUES DE PAD4
  申请人：PADLOCK THERAPEUTICS INC

  公开号：WO2017100594A1

  公开（公告）日：2017-06-15

  The present invention provides compounds useful as inhibitors of PAD4, compositions thereof, and methods of treating PAD4-related disorders.

  本发明提供了用作PAD4抑制剂的化合物、其组合物以及治疗与PAD4相关疾病的方法。
• Design of a Janus Kinase 3 (JAK3) Specific Inhibitor 1-((2<i>S</i>,5<i>R</i>)-5-((7<i>H</i>-Pyrrolo[2,3-<i>d</i>]pyrimidin-4-yl)amino)-2-methylpiperidin-1-yl)prop-2-en-1-one (PF-06651600) Allowing for the Interrogation of JAK3 Signaling in Humans
  作者：Atli Thorarensen、Martin E. Dowty、Mary Ellen Banker、Brian Juba、Jason Jussif、Tsung Lin、Fabien Vincent、Robert M. Czerwinski、Agustin Casimiro-Garcia、Ray Unwalla、John I. Trujillo、Sidney Liang、Paul Balbo、Ye Che、Adam M. Gilbert、Matthew F. Brown、Matthew Hayward、Justin Montgomery、Louis Leung、Xin Yang、Sarah Soucy、Martin Hegen、Jotham Coe、Jonathan Langille、Felix Vajdos、Jill Chrencik、Jean-Baptiste Telliez

  DOI：10.1021/acs.jmedchem.6b01694

  日期：2017.3.9

  kinase inhibitors resulting in several compounds entering clinical development and two FDA approved NMEs. However, despite significant effort during the past 2 decades, identification of highly selective JAK3 inhibitors has eluded the scientific community. A significant effort within our research organization has resulted in the identification of the first orally active JAK3 specific inhibitor, which

  致力于发现JAK激酶抑制剂的重要工作导致了几种化合物进入临床开发阶段，以及两个FDA批准的NME。然而，尽管在过去的20年中付出了巨大的努力，但高度选择性的JAK3抑制剂的鉴定仍未引起科学界的重视。我们研究机构的一项重大工作已导致鉴定出第一种口服活性JAK3特异性抑制剂，该抑制剂通过与独特的JAK3残基Cys-909共价相互作用而达到JAK同工型特异性。JAK3酶的相对较快的再合成速率在设计具有适当药效学性质以及有限的不需要的脱靶反应性的共价抑制剂时，提出了独特的挑战。经过努力，确定了11个（PF-06651600）是一种有效的低清除率化合物，具有体内功效。此JAK3特异性抑制剂11的良好疗效和安全性导致了其在多项人类临床研究中的评估。
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2010059658A1

  公开（公告）日：2010-05-27

  The invention is directed to 6-(4-pyιϊmidinyl)-1 H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1 - R4 are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  这项发明涉及6-(4-吡咯嗪基)-1 H-吲唑衍生物。具体而言，该发明涉及符合式(I)的化合物，其中R1-R4在此处被定义。该发明的化合物是PDK1的抑制剂，可用于治疗由于恒定激活的ACG激酶所特征化的免疫和代谢性疾病和紊乱，如癌症，更具体地说是乳腺癌、结肠癌和肺癌。因此，该发明进一步涉及包括该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包括该发明化合物的药物组合物来抑制PDK1活性和治疗相关疾病的方法。
• [EN] HETEROARYL INHIBITORS OF PAD4<br/>[FR] INHIBITEURS HÉTÉROARYLES DE PAD4
  申请人：PADLOCK THERAPEUTICS INC

  公开号：WO2017147102A1

  公开（公告）日：2017-08-31

  The present invention provides compounds useful as inhibitors of PAD4, compositions thereof, and methods of treating PAD4-related disorders.

  本发明提供了作为PAD4抑制剂有用的化合物，其组成物，以及治疗PAD4相关疾病的方法。
• [EN] MACROCYCLIC INHIBITORS OF PEPTIDYLARGININE DEIMINASES<br/>[FR] INHIBITEURS MACROCYCLIQUES DE PEPTIDYLARGININE DÉIMINASES
  申请人：GILEAD SCIENCES INC

  公开号：WO2021222353A1

  公开（公告）日：2021-11-04

  The present disclosure relates to novel compounds for use in therapeutic treatement of a disease associated with peptidylarginine deiminases (PADs), such as peptidylarginine deiminase type 4 (PAD4). The present disclosure also relates to processes and intermediates for the preparation of such compounds, methods of using such compounds and pharmaceutical compositions comprising the compounds described herein.

  本公开涉及用于治疗与肽精氨酸脱亚氨酶（PADs）相关的疾病的新化合物，例如肽精氨酸脱亚氨酶类型4（PAD4）。本公开还涉及用于制备这些化合物的过程和中间体，使用这些化合物的方法以及包含所述化合物的药物组合物。