(3S,6R)-3-methyl 1-(phenylmethyl) 6-methyl-1,3-piperidinedicarboxylate | 1227916-30-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3S,6R)-3-methyl 1-(phenylmethyl) 6-methyl-1,3-piperidinedicarboxylate
• 英文别名: cis-1-Benzyl 3-methyl 6-methylpiperidine-1,3-dicarboxylate；1-O-benzyl 3-O-methyl (3S,6R)-6-methylpiperidine-1,3-dicarboxylate
• CAS: 1227916-30-4
• 化学式: C₁₆H₂₁NO₄
• 分子量: 291.347
• InChiKey: IJRRKWFHSQQJIY-OCCSQVGLSA-N

物化性质

• 沸点：
  397.0±42.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,6R)-3-methyl 1-(phenylmethyl) 6-methyl-1,3-piperidinedicarboxylate 在 四(三苯基膦)钯 、 lithium hydroxide monohydrate 、 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 、 一水合肼 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 异丙醇 为溶剂， 100.0 ℃ 、448.17 kPa 条件下， 反应 44.5h， 生成 GSK2334470游离态
  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 、 氢气 作用下， 以 甲醇 、 二氧化碳 、 水 、 异丙醇 为溶剂， 15.0~25.0 ℃ 、413.7 kPa 条件下， 反应 4.5h， 生成 (3S,6R)-3-methyl 1-(phenylmethyl) 6-methyl-1,3-piperidinedicarboxylate
  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] N-ACYL PYRIDINE BIARYL COMPOUNDS AND THEIR USES<br/>[FR] COMPOSÉS DE N-ACYL PYRIDINE BIARYL ET LEURS UTILISATIONS
  申请人：NOVARTIS AG

  公开号：WO2012101063A1

  公开（公告）日：2012-08-02

  The present invention provides a compound of general formula:wherein Z2-Z6 include one or two nitrogen atoms as described herein, including pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds.

  本发明提供了一种通式化合物：其中Z2-Z6包括一个或两个如本文所述的氮原子，包括药学上可接受的盐、对映体、立体异构体、转型异构体、互变异构体或其外消旋体。这些化合物抑制CDK9的活性，因此可用作药物。还提供了使用通式I及其异构体治疗由CDK9介导的疾病或症状的方法，以及包含这些化合物的药物组合物。
• [EN] N-ACYL PYRIMIDINE BIARYL COMPOUNDS AS PROTEIN KINASE INHIBITORS<br/>[FR] COMPOSÉS À BASE DE N-ACYL-PYRIMIDINE-BIARYL CONVENANT COMME INHIBITEURS DE PROTÉINE KINASE
  申请人：NOVARTIS AG

  公开号：WO2012101064A1

  公开（公告）日：2012-08-02

  The present invention provides a compound of the general formula (1): wherein one of X and Y is N and the other is an optionally substituted carbon atom, and Z2-Z5 represent one or two nitrogen atoms, as further described herein, including pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals and as components of pharmaceutical compositions. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds described herein or pharmaceutical compositions comprising such compounds.

  本发明提供了一般式（1）的化合物：其中X和Y中的一个是N，另一个是可选择取代的碳原子，Z2-Z5代表一个或两个氮原子，如本文进一步描述的那样，包括药学上可接受的盐、对映体、立体异构体、转型异构体、互变异构体或其混合物。这些化合物抑制CDK9的活性，因此可用作药物和药物组合物的组分。还提供了使用本文描述的化合物或包含这些化合物的药物组合物治疗由CDK9介导的疾病或症状的方法。
• [EN] HETEROARYL COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS D'HÉTÉROARYLE EN TANT QU'INHIBITEURS DE KINASE
  申请人：NOVARTIS AG

  公开号：WO2011026917A1

  公开（公告）日：2011-03-10

  The present invention provides a compound of Formula (I): and pharmaceutically acceptable salts thereof. Also provided is a method of using a compound of Formula I for treating a disease or condition mediated by a CDK inhibitor.

  本发明提供了一种公式(I)的化合物：以及药用可接受的盐。还提供了一种使用公式I化合物治疗由CDK抑制剂介导的疾病或病症的方法。
• CHEMICAL COMPOUNDS
  申请人：Axten Jeffrey Michael

  公开号：US20110275611A1

  公开（公告）日：2011-11-10

  The invention is directed to 6-(4-pyrimidinyl)-1H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R 1 -R 4 are defined herein. The compounds of the invention axe 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

  本发明涉及6-(4-嘧啶基)-1H-吲唑衍生物。具体而言，本发明涉及公式（I）中R1-R4所定义的化合物。本发明的化合物是PDK1的抑制剂，可用于治疗免疫和代谢性疾病和障碍，这些疾病和障碍以恒定激活的ACG激酶为特征，例如乳腺、结肠和肺癌等。因此，本发明还涉及包含本发明化合物的制药组合物。本发明还涉及使用本发明化合物或包含本发明化合物的制药组合物抑制PDK1活性和治疗相关障碍的方法。
• Heteroaryl Compounds as Kinase Inhibitors
  申请人：Pfister Keith B.

  公开号：US20120157433A1

  公开（公告）日：2012-06-21

  The present invention provides a compound of Formula (I): and pharmaceutically acceptable salts thereof. Also provided is a method of using a compound of Formula I for treating a disease or condition mediated by a CDK inhibitor.

  本发明提供了一种公式(I)的化合物及其药学上可接受的盐。同时提供了一种使用公式I的化合物治疗由CDK抑制剂介导的疾病或病况的方法。