(2S,5R)-benzyl 5-(t-butoxycarbonylamino)-2-methylpiperidine-1-carboxylate | 1207853-21-1

• 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: (2S,5R)-benzyl 5-(t-butoxycarbonylamino)-2-methylpiperidine-1-carboxylate
• 英文别名: phenylmethyl (2S,5R)-5-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2-methyl-1-piperidinecarboxylate；benzyl (2S,5R)-5-[(tert-butoxycarbonyl)amino]-2-methylpiperidine-1-carboxylate；benzyl (2S,5R)-5-((tert-butoxycarbonyl)amino)-2-methylpiperidine-1-carboxylate；benzyl (2S,5R)-2-methyl-5-[(2-methylpropan-2-yl)oxycarbonylamino]piperidine-1-carboxylate
• CAS: 1207853-21-1
• 化学式: C₁₉H₂₈N₂O₄
• 分子量: 348.442
• InChiKey: GRCXWFCHLUQNEW-GOEBONIOSA-N

物化性质

• 沸点：
  477.4±44.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,5R)-benzyl 5-(t-butoxycarbonylamino)-2-methylpiperidine-1-carboxylate 以95的产率得到benzyl 5-amino-2-methylpiperidine-1-carboxylate
  参考文献：
  名称：

  PYRROLO[2,3-D]PYRIMIDINYL, PYRROLO[2,3-B]PYRAZINYL AND PYR-ROLO[2,3-D]PYRIDINYL ACRYLAMIDES

  摘要：

  本发明提供了具有药理活性的吡咯[2,3-d]嘧啶基和吡咯[2,3-d]吡啶基丙烯酰胺及其类似物。这些化合物对于抑制Janus激酶（JAK）具有用处。本发明还涉及包含制备这些化合物的方法和治疗和预防由JAK介导的疾病的方法的组合物。

  公开号：

  US20150158864A1
• 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 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氧化碳 、 水 、 异丙醇 、 叔丁醇 为溶剂， 15.0~100.0 ℃ 、413.7 kPa 条件下， 反应 24.5h， 生成 (2S,5R)-benzyl 5-(t-butoxycarbonylamino)-2-methylpiperidine-1-carboxylate
  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] 6 SUBSTITUTED 2-HETEROCYCLYLAMINO PYRAZINE COMPOUNDS AS CHK-1 INHIBITORS<br/>[FR] COMPOSÉS 2-HÉTÉROCYCLYLAMINO PYRAZINES SUBSTITUÉES EN POSITION 6 EN TANT QU'INHIBITEURS DE CHK-1
  申请人：PFIZER

  公开号：WO2010016005A1

  公开（公告）日：2010-02-11

  The present invention is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, their synthesis, and their use as CHK-1 inhibitors.

  本发明涉及式(I)的化合物，及其药用可接受的盐，它们的合成以及它们作为CHK-1抑制剂的用途。
• Process Development and Scale Up of a Selective JAK3 Covalent Inhibitor PF-06651600
  作者：Yong Tao、J. Christopher McWilliams、Kristin E. Wiglesworth、Kevin P. Girard、Teresa M. Makowski、Neal W. Sach、Jason G. Mustakis、Ruchi Mehta、John I. Trujillo、Xiaofeng Chen、Tangqing Li、Feng Shi、Chengfu Xie、Qing Zhang

  DOI：10.1021/acs.oprd.9b00198

  日期：2019.9.20

  cis-isomer directly from a racemic mixture of cis/trans isomers, (3) a high yielding amidation via Schotten–Baumann conditions, and (4) critical development of a reproducible crystallization procedure for a stable crystalline salt (1·TsOH), which is suitable for long-term storage and tablet formulation. All chromatographic purifications, including two chiral SFC chromatographic separations, were eliminated.

  通过成功启用第一代合成技术，已经开发了PF-06651600（1）的可扩展过程。合成亮点包括：（1）用较便宜的5％Rh / C催化剂代替昂贵的PtO 2进行吡啶加氢；（2）鉴定非对映体盐结晶，以便直接从对映体中分离出对映体纯的顺式异构体。顺式/反式异构体的外消旋混合物，（3）通过Schotten-Baumann条件产生高产率的酰胺化反应，以及（4）稳定结晶盐（1·TsOH）的可重现结晶过程的关键发展），适合长期存放和片剂配制。消除了所有色谱纯化，包括两次手性SFC色谱分离。与合成的每个步骤中的其他改进相结合，总产率从5％提高到14％。已交付了几百千克的API多批次产品，以支持临床研究。
• 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。
• 6 SUBSTITUTED 2- HETEROCYCLYLAMINO PYRAZINE COMPOUNDS AS CHK-1 INHIBITORS
  申请人：Braganza John Frederick

  公开号：US20110144084A1

  公开（公告）日：2011-06-16

  The present invention is directed to compounds of formula (I), and pharmaceutically acceptable salts thereof, their synthesis, and their use as CHK-1 inhibitors.

  本发明涉及式（I）化合物及其药学上可接受的盐，它们的合成以及它们作为CHK-1抑制剂的用途。
• Chemical compounds
  申请人：Axten Jeffrey Michael

  公开号：US08697685B2

  公开（公告）日：2014-04-15

  The invention is directed to 6-(4-pyrimidinyl)-1H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1-R4 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，例如乳腺癌、结肠癌和肺癌等癌症。因此，本发明进一步涉及包括本发明化合物的药物组合物。本发明还涉及使用本发明化合物或包括本发明化合物的药物组合物来抑制PDK1活性和治疗与之相关的疾病的方法。