methyl 2-amino-5-(1-(1-methylpiperidin-4-yl)pyrazol-4-yl)nicotinate | 1146950-56-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: methyl 2-amino-5-(1-(1-methylpiperidin-4-yl)pyrazol-4-yl)nicotinate
• 英文别名: methyl 2-amino-5-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]pyridine-3-carboxylate；methyl 2-amino-5-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]pyridine-3-carboxylate
• CAS: 1146950-56-2
• 化学式: C₁₆H₂₁N₅O₂
• 分子量: 315.375
• InChiKey: AQMWAXFCOSRNLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-amino-5-(1-(1-methylpiperidin-4-yl)pyrazol-4-yl)nicotinate 在 盐酸 、 氢氧化钾 作用下， 以 甲醇 、 水 为溶剂， 生成 2-amino-5-[1-(1-methyl-4-piperidyl)pyrazol-4-yl]pyridine-3-carboxylic acid
  参考文献：
  名称：

  PYRIDINE AND PYRAZINE DERIVATIVES - 083

  摘要：

  本发明涉及式I的吡啶和吡嗪衍生物 或其药用可接受的盐，其中W、G 1 、G 2 、G 3 、G 4 、J、环A、n和R 3 各自具有如前文描述中定义的任何含义；它们的制备过程，包含它们的药物组合物以及它们在制造用于治疗细胞增殖性障碍的药物中的应用。

  公开号：

  US20090118305A1
• 作为产物：
  描述：

  2-氨基-5-溴烟酸甲酯 在 盐酸 、 四(三苯基膦)钯 、 三乙酰氧基硼氢化钠 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 27.0h， 生成 methyl 2-amino-5-(1-(1-methylpiperidin-4-yl)pyrazol-4-yl)nicotinate
  参考文献：
  名称：

  Discovery of 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1,2,4-triazol-3-yl)piperidin-1-yl)-3-hydroxypropan-1-one (AZD8835): A potent and selective inhibitor of PI3Kα and PI3Kδ for the treatment of cancers

  摘要：

  Starting from potent inhibitors of PI3K alpha having poor general kinase selectivity (e.g., 1 and 2), optimisation of this series led to the identification of 25, a potent inhibitor of PI3K alpha (wild type, E545K and H1047R mutations) and PI3K delta, selective versus PI3K beta and PI3K gamma, with excellent general kinase selectivity. Compound 25 displayed low metabolic turnover and suitable physical properties for oral administration. In vivo, compound 25 showed pharmacodynamic modulation of AKT phosphorylation and near complete inhibition of tumour growth (93% tumour growth inhibition) in a murine H1047R PI3K alpha mutated SKOV-3 xenograft tumour model after chronic oral administration at 25 mg/kg b.i.d. Compound 25, also known as AZD8835, is currently in phase I clinical trials. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.002

文献信息

• Pyridine and pyrazine derivatives -083
  申请人：AstraZeneca AB

  公开号：US08017611B2

  公开（公告）日：2011-09-13

  The invention concerns pyridine and pyrazine derivatives of Formula I or a pharmaceutically-acceptable salt thereof, wherein each of W, G1, G2, G3, G4, J, Ring A, n and R3 has any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.

  本发明涉及式I的吡啶和吡嗪衍生物或其药学上可接受的盐，其中W、G1、G2、G3、G4、J、环A、n和R3中的每一个都具有前述描述中的任何含义；它们的制备方法，包含它们的制药组合物以及它们在制造用于治疗细胞增殖性疾病的药物中的使用。
• PYRIDINE AND PYRAZINE DERIVATIVES USEFUL IN THE TREATMENT OF CELL PROLIFERATIVE DISORDERS
  申请人：AstraZeneca AB

  公开号：EP2215085B1

  公开（公告）日：2011-09-07
• US8017611B2
  申请人：——

  公开号：US8017611B2

  公开（公告）日：2011-09-13
• [EN] PYRIDINE AND PYRAZINE DERIVATIVES - 083<br/>[FR] DÉRIVÉS DE PYRIDINE ET DE PYRAZINE - 083
  申请人：ASTRAZENECA AB

  公开号：WO2009053737A2

  公开（公告）日：2009-04-30

  The invention concerns pyridine a nd pyrazine derivatives of Formula (I) or a pharmaceutically-acceptable salt thereof, wherein each of W, G1, G 2, G3, G4, J, Ring A, n and R 3 has any of the meanings defined hereinbefo re in the description; processes for their preparation, pharmaceutical compositions containi ng them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.
• Discovery of 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1,2,4-triazol-3-yl)piperidin-1-yl)-3-hydroxypropan-1-one (AZD8835): A potent and selective inhibitor of PI3Kα and PI3Kδ for the treatment of cancers
  作者：Bernard Barlaam、Sabina Cosulich、Bénédicte Delouvrié、Rebecca Ellston、Martina Fitzek、Hervé Germain、Stephen Green、Urs Hancox、Craig S. Harris、Kevin Hudson、Christine Lambert-van der Brempt、Honorine Lebraud、Françoise Magnien、Maryannick Lamorlette、Antoine Le Griffon、Rémy Morgentin、Gilles Ouvry、Ken Page、Georges Pasquet、Urszula Polanska、Linette Ruston、Twana Saleh、Michel Vautier、Lara Ward

  DOI：10.1016/j.bmcl.2015.10.002

  日期：2015.11

  Starting from potent inhibitors of PI3K alpha having poor general kinase selectivity (e.g., 1 and 2), optimisation of this series led to the identification of 25, a potent inhibitor of PI3K alpha (wild type, E545K and H1047R mutations) and PI3K delta, selective versus PI3K beta and PI3K gamma, with excellent general kinase selectivity. Compound 25 displayed low metabolic turnover and suitable physical properties for oral administration. In vivo, compound 25 showed pharmacodynamic modulation of AKT phosphorylation and near complete inhibition of tumour growth (93% tumour growth inhibition) in a murine H1047R PI3K alpha mutated SKOV-3 xenograft tumour model after chronic oral administration at 25 mg/kg b.i.d. Compound 25, also known as AZD8835, is currently in phase I clinical trials. (C) 2015 Elsevier Ltd. All rights reserved.