4-(3-甲基脲)苯硼酸频哪酯 | 874290-99-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(3-甲基脲)苯硼酸频哪酯
• 中文别名: 4-(3-甲基脲)苯基硼酸频哪醇酯
• 英文名称: 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea
• 英文别名: 1-methyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea
• CAS: 874290-99-0
• 化学式: C₁₄H₂₁BN₂O₃
• 分子量: 276.143
• InChiKey: MRHQTDZUJNAZGQ-UHFFFAOYSA-N

物化性质

• 熔点：
  183-187
• 沸点：
  378.3±34.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.74
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2934999090
• 危险性防范说明：
  P233,P260,P261,P264,P270,P271,P280,P301+P312,P302+P352,P304,P304+P340,P305+P351+P338,P312,P321,P330,P332+P313,P337+P313,P340,P362,P403,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  2-8°C

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: 4-(3-Methylureido)phenylboronic acid, pinacol ester
Synonyms: 1-Methyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: 4-(3-Methylureido)phenylboronic acid, pinacol ester
CAS number: 874290-99-0

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C14H21BN2O3
Molecular weight: 276.1

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  4-(3-甲基脲)苯硼酸频哪酯 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 16.0h， 生成 1-[4-[4-(cyclohexylsulfanylmethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-methyl-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
• 作为产物：
  描述：

  4-氨基苯硼酸频哪醇酯 在 吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 4-(3-甲基脲)苯硼酸频哪酯
  参考文献：
  名称：

  TRIAZINE COMPOUNDS AS PI3 KINASE AND MTOR INHIBITORS

  摘要：

  式I化合物，其中：R1为，R2、R4和R6-9如本文所定义，以及其药学上可接受的盐和酯。这些化合物抑制PI3激酶和mTOR，并可用于治疗由PI3激酶和mTOR介导的疾病，例如多种癌症。本发明还公开了制备和使用这些化合物的方法。此外，还公开了含有本发明化合物的各种组合物。

  公开号：

  US20170119778A1

文献信息

• [EN] QUINAZOLINES AND AZAQUINAZOLINES AS DUAL INHIBITORS OF RAS/RAF/MEK/ERK AND PI3K/AKT/PTEN/MTOR PATHWAYS<br/>[FR] QUINAZOLINES ET AZAQUINAZOLINES EN TANT QUE DOUBLES INHIBITEURS DES VOIES RAS/RAF/MEK/ERK ET PI3K/AKT/PTEN/MTOR
  申请人：ASANA BIOSCIENCES LLC

  公开号：WO2014169167A1

  公开（公告）日：2014-10-16

  The present application provides novel quinazolines and azaquinazolines and pharmaceutically acceptable salts thereof. Also provided are methods for preparing these compounds. These compounds are useful in for co-regulating RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways by administering a therapeutically effective amount of one or more of the compounds of formula (I), wherein X, Y, T and R4, and R6 to R8' are defined herein, to a patient. By doing so, these compounds are effective in treating conditions associated with the dysregulation of the RAS/RAF/MEK/ERK and PI3K/AKT/PTEN/mTOR pathways. A variety of conditions can be treated using these compounds and include diseases which are characterized by abnormal cellular proliferation. In one embodiment/ the disease is cancer.

  本申请提供了新型喹唑啉和氮杂喹唑啉及其药用可接受盐。还提供了制备这些化合物的方法。通过向患者投与式有效量的式(I)化合物中的一个或多个，其中X、Y、T和R4，以及R6到R8'在此处定义，来共同调节RAS/RAF/MEK/ERK和PI3K/AKT/PTEN/mTOR途径。通过这样做，这些化合物在治疗与RAS/RAF/MEK/ERK和PI3K/AKT/PTEN/mTOR途径失调相关的疾病方面是有效的。可以使用这些化合物治疗各种疾病，包括以异常细胞增殖为特征的疾病。在一个实施例中，该疾病是癌症。
• DIHYROFUROPYRMINDINE COMPOUNDS
  申请人：DONG Qing

  公开号：US20110021515A1

  公开（公告）日：2011-01-27

  The present invention provides mTOR inhibitors of the formula wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods of making the compounds and intermediates thereof; and methods of using the compounds.

  本发明提供了式的mTOR抑制剂 其中变量如本文所定义。还提供了包含这些化合物的药物组合物、试剂盒和制造品；制备这些化合物及其中间体的方法；以及使用这些化合物的方法。
• [EN] DIHYDROFUROPYRIMIDINE COMPOUNDS<br/>[FR] COMPOSÉS DE DIHYDROFUROPYRIMIDINE
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2012099581A1

  公开（公告）日：2012-07-26

  The present invention provides mTOR inhibitors of the formula (I) wherein the variables are as defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds; methods of making the compounds and intermediates thereof; and methods of using the compounds.

  本发明提供了式(I)的mTOR抑制剂，其中变量如本文所定义。还提供了包含这些化合物的药物组合物、试剂盒和制造品；制备这些化合物及其中间体的方法；以及使用这些化合物的方法。
• Discovery of 4-Morpholino-6-aryl-1<i>H</i>-pyrazolo[3,4-<i>d</i>]pyrimidines as Highly Potent and Selective ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin (mTOR): Optimization of the 6-Aryl Substituent
  作者：Jeroen C. Verheijen、David J. Richard、Kevin Curran、Joshua Kaplan、Mark Lefever、Pawel Nowak、David J. Malwitz、Natasja Brooijmans、Lourdes Toral-Barza、Wei-Guo Zhang、Judy Lucas、Irwin Hollander、Semiramis Ayral-Kaloustian、Tarek S. Mansour、Ker Yu、Arie Zask

  DOI：10.1021/jm9013828

  日期：2009.12.24

  6-alkylureidophenyl groups with 1-carbamoylpiperidine substitution resulted in compounds with subnanomolar IC50 against mTOR and greater than 1000-fold selectivity over PI3K-α. In addition, structure based drug design resulted in the preparation of several 6-arylureidophenyl-1H-pyrazolo[3,4-d]pyrimidines, substituted in the 4-position of the arylureido moiety with water solubilizing groups. These compounds

  设计和合成了一系列4-吗啉代-6-芳基-1 H-吡唑并[3,4- d ]嘧啶，它们是雷帕霉素（mTOR）哺乳动物靶标的有效和选择性抑制剂。优化6-芳基取代基导致发现带有6-脲基苯基的抑制剂，这是第一个报道的具有亚纳摩尔抑制浓度的mTOR活性位点抑制剂。本文提供的数据表明，6-芳基脲基苯基取代基可产生有效的mTOR和磷脂酰肌醇3-激酶α（PI3K-α）混合抑制剂，而6-烷基脲基苯基附肢则具有高度选择性的mTOR抑制剂。6-烷基脲基苯基与1-氨基甲酰基哌啶取代的组合产生具有亚纳摩尔级IC 50的化合物对mTOR的抗性和对PI3K-α的选择性大于1000倍。另外，基于结构的药物设计导致制备了几种6-芳基脲基苯基-1H-吡唑并[3，4- d ]嘧啶，其在芳基脲基部分的4-位被水溶性基团取代。这些化合物将有效的mTOR抑制（IC 50 <1 nM）与细胞增殖试验（IC 50 <1 nM）中前所未有的活性结合在一起。
• PYRROLO[3,2-d]PYRIMIDINE COMPOUNDS AND THEIR USE AS PI3 KINASE AND mTOR KINASE INHIBITORS
  申请人：CHEN Zecheng

  公开号：US20090149458A1

  公开（公告）日：2009-06-11

  A pyrrolo[3,2-d]pyrimidine compound, such as a compound of the formula (I): or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.

  一种吡咯并[3,2-d]嘧啶化合物，例如具有以下式（I）的化合物：或其药用可接受的盐，其中构成变量如本文所定义，包括所述化合物的组合物，以及制备和使用所述化合物的方法。