4-(3-cyclopropylureido)phenyl boronic acid | 1009629-18-8

• 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: 4-(3-cyclopropylureido)phenyl boronic acid
• 英文别名: [4-(3-Cyclopropylureido)phenyl]boronic acid；[4-(cyclopropylcarbamoylamino)phenyl]boronic acid
• CAS: 1009629-18-8
• 化学式: C₁₀H₁₃BN₂O₃
• 分子量: 220.036
• InChiKey: WGNRKLHVNQWTQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.35
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  81.6
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-(2-chloro-6-(3-methylmorpholino)pyrimidin-4-yl)methanol 、 4-(3-cyclopropylureido)phenyl boronic acid 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以83%的产率得到3-cyclopropyl-1-[4-[4-(hydroxymethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]urea
  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

• [EN] MORPHOLINO SUBSTITUTED UREA OR CARBAMATE DERIVATIVES AS MTOR INHIBITORS<br/>[FR] URÉE SUBSTITUÉE PAR UN GROUPE MORPHOLINO OU DÉRIVÉS CARBAMATE COMME INHIBITEURS DE MTOR
  申请人：CELLZOME LTD

  公开号：WO2013041652A1

  公开（公告）日：2013-03-28

  The invention relates to compounds of formula (I), wherein m, n, R 1, T 0 and T 1 have the meaning as cited in the description and the claims. Said compounds are useful as inhibitors of mTOR for the treatment or prophylaxis of mTOR related diseases and disorders. The invention also relates to pharmaceutical compositions including said compounds as well as the use as medicaments.

  本发明涉及公式（I）的化合物，其中m，n，R1，T0和T1的含义如所述描述和权利要求中所述。所述化合物可用作mTOR的抑制剂，用于治疗或预防与mTOR相关的疾病和障碍。本发明还涉及包括该化合物的制药组合物以及用作药物的用途。
• MORPHOLINO SUBSTITUTED UREA OR CARBAMATE DERIVATIVES AS MTOR INHIBITORS
  申请人：Lynch Rosemary

  公开号：US20140378438A1

  公开（公告）日：2014-12-25

  The invention relates to compounds of formula (I) wherein m, n, R 1 , T 0 and T 1 have the meaning as cited in the description and the claims. The compounds are useful as inhibitors of mTOR for the treatment or prophylaxis of mTOR related diseases and disorders. The invention also relates to pharmaceutical compositions including said compounds as well as methods of treating mTOR related diseases.

  本发明涉及式（I）的化合物，其中m，n，R1，T0和T1的含义如所述描述和权利要求中所述。该化合物可用作mTOR的抑制剂，用于治疗或预防与mTOR相关的疾病和障碍。本发明还涉及包括所述化合物的制药组合物以及治疗mTOR相关疾病的方法。
• Transcutaneous immunostimulation
  申请人：Finlay Maurice Raymond Verschoyle

  公开号：US20080171743A1

  公开（公告）日：2008-07-17

  A compound of formula (I) or a pharmaceutically 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.

  公式为（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用途，例如在治疗增生性疾病如癌症和特别是由mTOR激酶和/或一个或多个PI3K酶介导的疾病中的用途。
• Compounds-943
  申请人：AstraZeneca AB

  公开号：US07750003B2

  公开（公告）日：2010-07-06

  A compound of formula (I) or a pharmaceutically 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，例如在治疗增生性疾病如癌症中，特别是在由mTOR激酶和/或一个或多个PI3K酶介导的疾病中。
• Discovery of AZD3147: A Potent, Selective Dual Inhibitor of mTORC1 and mTORC2
  作者：Kurt G. Pike、Jeff Morris、Linette Ruston、Sarah L. Pass、Ryan Greenwood、Emma J. Williams、Julie Demeritt、Janet D. Culshaw、Kristy Gill、Martin Pass、M. Raymond V. Finlay、Catherine J. Good、Craig A. Roberts、Gordon S. Currie、Kevin Blades、Jonathan M. Eden、Stuart E. Pearson

  DOI：10.1021/jm501778s

  日期：2015.3.12

  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.