3-[[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methylsulfanyl]propan-1-ol | 1099703-76-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-[[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methylsulfanyl]propan-1-ol
• CAS: 1099703-76-0
• 化学式: C₁₃H₂₀ClN₃O₂S
• 分子量: 317.84
• InChiKey: OQXFLDKRDYIHRU-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  83.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-[[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methylsulfanyl]propan-1-ol 在 咪唑 、 bis-triphenylphosphine-palladium(II) chloride 、 四丁基氟化铵 、 四丁基溴化铵 、 sodium carbonate 、 三乙胺 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 35.0h， 生成 3-(2-hydroxyethyl)-1-[4-[4-[1-(3-hydroxypropylsulfonyl)cyclopropyl]-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]thiourea
  参考文献：
  名称：

  Discovery of AZD3147: A Potent, Selective Dual Inhibitor of mTORC1 and mTORC2

  摘要：

  High throughput screening followed by a lead generation campaign uncovered a novel series of urea containing morpholinopyrimidine compounds which act as potent and selective dual inhibitors of mTORC1 and mTORC2. We describe the continued compound optimization campaign for this series, in particular focused on identifying compounds with improved cellular potency, improved aqueous solubility, and good stability in human hepatocyte incubations. Knowledge from empirical SAR investigations was combined with an understanding of the molecular interactions in the crystal lattice to improve both cellular potency and solubility, and the composite parameters of LLE and pIC(50)-pSolubility were used to assess compound quality and progress. Predictive models were employed to efficiently mine the attractive chemical space identified resulting in the discovery of 42 (AZD3147), an extremely potent and selective dual inhibitor of mTORC1 and mTORC2 with physicochemical and pharmacokinetic properties suitable for development as a potential clinical candidate.

  DOI：

  10.1021/jm501778s
• 作为产物：
  描述：

  2,6-二氯嘧啶-4-甲酸甲酯 在 锂硼氢 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 41.35h， 生成 3-[[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methylsulfanyl]propan-1-ol
  参考文献：
  名称：

  Discovery of AZD3147: A Potent, Selective Dual Inhibitor of mTORC1 and mTORC2

  摘要：

  High throughput screening followed by a lead generation campaign uncovered a novel series of urea containing morpholinopyrimidine compounds which act as potent and selective dual inhibitors of mTORC1 and mTORC2. We describe the continued compound optimization campaign for this series, in particular focused on identifying compounds with improved cellular potency, improved aqueous solubility, and good stability in human hepatocyte incubations. Knowledge from empirical SAR investigations was combined with an understanding of the molecular interactions in the crystal lattice to improve both cellular potency and solubility, and the composite parameters of LLE and pIC(50)-pSolubility were used to assess compound quality and progress. Predictive models were employed to efficiently mine the attractive chemical space identified resulting in the discovery of 42 (AZD3147), an extremely potent and selective dual inhibitor of mTORC1 and mTORC2 with physicochemical and pharmacokinetic properties suitable for development as a potential clinical candidate.

  DOI：

  10.1021/jm501778s

文献信息

• Compounds - 945
  申请人：PIKE Kurt Gordon

  公开号：US20090018134A1

  公开（公告）日：2009-01-15

  A compound of formula (I) or a pharamaceutically acceptable salt thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, for example in the treatment of proliferative disease such as cancer and particularly in disease mediated by an mTOR kinase and/or one or more PI3K enzyme.

  公式（I）的化合物或其药用盐，其制备方法，含有它们的药物组合物以及它们在治疗中的用途，例如在治疗增殖性疾病如癌症，特别是由mTOR激酶和/或一个或多个PI3K酶介导的疾病。
• [EN] MORPHOLINO PYRIMIDINE DERIVATIVES USED IN DISEASES LINKED TO MTOR KINASE AND/OR PI3K<br/>[FR] DÉRIVÉS DE MORPHOLINO PYRIMIDINE UTILISÉS DANS DES MALADIES LIÉES À UNE KINASE MTOR ET/OU À PI3K
  申请人：ASTRAZENECA AB

  公开号：WO2009007750A1

  公开（公告）日：2009-01-15

  A compound of formula (I) or a pharamaceutically acceptable salt thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, for example in the treatment of proliferative disease such as cancer and particularly in disease mediated by an mTOR kinase and/or one or more PI3K enzyme.

  化合物式(I)或其药学上可接受的盐，其制备方法，含有它们的药物组合物以及它们在治疗中的应用，例如在治疗增殖性疾病，如癌症，特别是由mTOR激酶和/或一个或多个PI3K酶介导的疾病中的使用。
• MORPHOLINO PYRIMIDINE DERIVATIVES USED IN DISEASES LINKED TO MTOR KINASE AND/OR PI3K
  申请人：Pike Kurt Gordon

  公开号：US20100249131A1

  公开（公告）日：2010-09-30

  A compound of formula (I) or a pharamaceutically acceptable salt thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, for example in the treatment of proliferative disease such as cancer and particularly in disease mediated by an mTOR kinase and/or one or more PI3K enzyme.

  式(I)的化合物或其药学上可接受的盐，其制备过程，包含它们的制药组合物以及它们在治疗中的应用，例如在治疗增殖性疾病如癌症，特别是由mTOR激酶和/或一个或多个PI3K酶介导的疾病中的应用。
• US8138183B2
  申请人：——

  公开号：US8138183B2

  公开（公告）日：2012-03-20