(2R)-1-[4-[5-[5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]-1-methyl-1,2,4-triazol-3-yl]-1-piperidyl]-3-hydroxy-2-methyl-propan-1-one | 1620576-67-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (2R)-1-[4-[5-[5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]-1-methyl-1,2,4-triazol-3-yl]-1-piperidyl]-3-hydroxy-2-methyl-propan-1-one
• 英文别名: (2R)-1-[4-[5-[5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]-1-methyl-1,2,4-triazol-3-yl]-1-piperidyl]-3-hydroxy-2-methylpropan-1-one；(2R)-1-[4-[5-[5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]-1-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]-3-hydroxy-2-methylpropan-1-one
• CAS: 1620576-67-1
• 化学式: C₂₂H₃₁N₉O₃
• 分子量: 469.547
• InChiKey: LOLDQPMMGNHKHJ-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  162
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (Z)-tert-butyl 4-(2-(amino(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)methylene)hydrazinecarbonyl)piperidine-1-carboxylate 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 2-甲基四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 57.08h， 生成 (2R)-1-[4-[5-[5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]-1-methyl-1,2,4-triazol-3-yl]-1-piperidyl]-3-hydroxy-2-methyl-propan-1-one
  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

• CHEMICAL COMPOUNDS
  申请人：ASTRAZENECA AB

  公开号：US20140206700A1

  公开（公告）日：2014-07-24

  The invention concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R 1 and R 2 have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.

  这项发明涉及公式(I)的化合物或其药用盐，其中R1和R2具有在描述中定义的任何含义；它们的制备方法，含有它们的药物组合物以及它们在治疗细胞增殖性疾病中的用途。
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2014114928A1

  公开（公告）日：2014-07-31

  The invention concerns compounds of Formula (I) (Formula (I)) or pharmaceutically-acceptable salts thereof, wherein R1 and R2 have any of the meanings defined herein before in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.

  该发明涉及Formula (I)的化合物（Formula (I)）或其药用盐，其中R1和R2具有在描述中定义的任何含义；它们的制备方法，含有它们的药物组合物以及它们在治疗细胞增殖性疾病中的用途。
• Chemical compounds
  申请人：ASTRAZENECA AB

  公开号：US09156831B2

  公开（公告）日：2015-10-13

  The invention concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1 and R2 have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.

  本发明涉及式（I）的化合物或其药学上可接受的盐，其中R1和R2具有上述描述中定义的任何含义；其制备方法，含有它们的制药组合物以及它们在治疗细胞增殖性疾病中的应用。
• Chemical Compounds
  申请人：AstraZeneca AB

  公开号：US20160137634A1

  公开（公告）日：2016-05-19

  The invention concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R 1 and R 2 have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.

  本发明涉及公式(I)的化合物或其药学上可接受的盐，其中R1和R2具有本说明书中定义的任何含义；它们的制备过程，包含它们的制药组合物以及它们在治疗细胞增殖性疾病方面的用途。
• US9156831B2
  申请人：——

  公开号：US9156831B2

  公开（公告）日：2015-10-13