4-(N-异丙基氨基羰基)苯硼酸 | 397843-67-3

• 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-(N-异丙基氨基羰基)苯硼酸
• 中文别名: 4-(N-异丙氨基羰基)苯硼酸；4-(异丙基氨甲酰基)苯硼酸
• 英文名称: 4-iso-propylaminocarbonylphenylboronic acid
• 英文别名: 4-(N-isopropylaminocarbonyl)phenylboronic acid；[4-(isopropylcarbamoyl)phenyl]boronic acid；[4-(propan-2-ylcarbamoyl)phenyl]boronic acid
• CAS: 397843-67-3
• 化学式: C₁₀H₁₄BNO₃
• mdl: MFCD04039353
• 分子量: 207.037
• InChiKey: GBCSEYKTZAKRMT-UHFFFAOYSA-N

物化性质

• 熔点：
  162-167°C
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.29
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• 海关编码：
  2931900090
• 安全说明：
  S26,S36/37/39
• 危险性防范说明：
  P233,P260,P261,P264,P271,P280,P302+P352,P304,P304+P340,P305+P351+P338,P312,P321,P332+P313,P337+P313,P340,P362,P403,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
4-(N-Isopropylaminocarbonyl)phenylboronic acid
Product Name:
Synonyms: N-Isopropyl 4-boronobenzamide

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
4-(N-Isopropylaminocarbonyl)phenylboronic acid
Ingredient name:
CAS number: 397843-67-3

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.
Storage: Store in closed vessels.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C10H14BNO3
Molecular weight: 207.0

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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：

  2-(5-bromo-8-methoxy-1,6-naphthyridin-7-yl)-5-(4-fluorobenzyl)-1,3,4-oxadiazole 、 4-(N-异丙基氨基羰基)苯硼酸 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  1,3,4-Oxadiazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 2: SAR of the C5 position

  摘要：

  The use of a 1,3,4-oxadiazole in combination with an 8-hydroxy-1,6-naphthyridine ring system has been shown to deliver potent enzyme and antiviral activity through inhibition of viral DNA integration. This report presents a detailed structure-activity investigation of the C5 position resulting in low nM potency for several analogs with an excellent therapeutic index. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.01.089
• 作为产物：
  描述：

  4-羧基苯硼酸 、 异丙胺 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.08h， 以78%的产率得到4-(N-异丙基氨基羰基)苯硼酸
  参考文献：
  名称：

  使用硼酸的液-液分配进行多步相转换合成：具有扩展的兼容反应库的生产性标签

  摘要：

  标记：已开发出一种用于相位开关合成的系统。硼酸官能度用作与山梨糖醇络合的相标签，并有助于化合物在高pH下从有机溶剂转移到水中。然后可以将相标签用于生产性反应步骤中以生成目标产物，从而消除了通过硅胶色谱纯化的过程。

  DOI：

  10.1002/anie.200906710

文献信息

• Universal Solid-Phase Approach for the Immobilization, Derivatization, and Resin-to-Resin Transfer Reactions of Boronic Acids
  作者：Michel Gravel、Kim A. Thompson、Mark Zak、Christian Bérubé、Dennis G. Hall

  DOI：10.1021/jo0106501

  日期：2002.1.1

  amides, anilides, and ureas, respectively. Ugi multicomponent reactions on DEAM-PS-supported aminobenzeneboronic acids, derivatization of multifunctional arylboronic acids, and sequential reactions can also be carried out efficiently. These new DEAM-PS-supported arylboronic acids can be employed directly into resin-to-resin transfer reactions (RRTR). This type of multiresin process helps eliminate time-consuming

  含硼酸的分子广泛用于生物学，医学和合成领域。然而，这些化合物往往难以通过溶液相方法处理。在此，该问题通过用于官能化硼酸的衍生化的第一种通用固相方法的开发来解决。该方法基于使用二乙醇胺树脂锚，该锚通过避免在酯化过程中彻底去除水的需要而促进了硼酸的固定。通过在室温下在无水溶剂中简单搅拌，可以在数分钟内将多种硼酸固定在N，N-二乙醇氨基甲基聚苯乙烯（DEAM-PS，1）上。通过（1）DEAM-PS负载的对甲苯基硼酸的（1）NMR分析显示了形成具有假定的NB配位的双环二乙醇胺硼酸酯的证据。通过紫外光谱研究了DEAM-PS树脂对相同型号硼酸的水解裂解。水解和附着显示在快速达到的平衡下发生，并且需要大量过量的水（> 32当量）以实现从DEAM-PS实际定量释放硼酸。尽管它们对水和醇具有相对的敏感性，但可以用甲酰基，溴甲基，羧基或氨基官能化的DEAM-PS结合的芳基硼酸以良好或极高的收率转化成各种胺，酰
• Discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as novel, highly potent and selective, orally bioavailable inhibitors of Tyrosine Threonine Kinase, TTK
  作者：Radoslaw Laufer、Sze-Wan Li、Yong Liu、Grace Ng、Yunhui Lang、Miklos Feher、Richard Brokx、Irina Beletskaya、Richard Hodgson、Guodong Mao、Olga Plotnikova、Donald E. Awrey、Jacqueline M. Mason、Xin Wei、Dan Chi-Chia Lin、Yi Che、Reza Kiarash、Brian Madeira、Graham C. Fletcher、Tak W. Mak、Mark R. Bray、Henry W. Pauls

  DOI：10.1016/j.bmcl.2016.06.021

  日期：2016.8

  Herein we report the discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as a potent, novel class of TTK inhibitors. The series was identified by means of bioisosteric replacement of the related imidazopyrazine and imidazopyridazine scaffolds. Optimization led to the identification of compounds with excellent potency (Ki = 0.8 nM) and exceptional kinase selectivity. The SAR indicates

  TTK / Mps1是通过参与有丝分裂纺锤体装配检查点来控制细胞分裂进程的关键激酶，在许多人类癌症中均过表达。在本文中，我们报告了4-（4-氨基吡唑并[1,5- a ] [1,3,5]三嗪-8-基）苯甲酰胺作为一种强力的新型TTK抑制剂的发现。该系列通过相关等价的咪唑并吡嗪和咪唑并哒嗪支架的生物立体置换来鉴定。通过优化，鉴定出具有出色效价（K i  = 0.8 nM）和出色的激酶选择性的化合物。SAR表示活动强烈依赖于N的存在-环丙基-2-甲基苯甲酰胺部分，描绘了1½型激酶抑制剂的几何形状。分子建模表明，通过氢键和疏水相互作用介导的广泛而最佳的接触是抑制剂的选择性和效力的原因。这些化合物在一组人类癌细胞系（HCT116 GI 50  <15 nM）中显示出强大的抗增殖活性，并具有良好的啮齿动物药代动力学（口服％F 97％）。
• Identification of Phosphorylation Consensus Sequences and Endogenous Neuronal Substrates of the Psychiatric Risk Kinase TNIK
  作者：Q. Wang、S. P. Amato、D. M. Rubitski、M. M. Hayward、B. L. Kormos、P. R. Verhoest、L. Xu、N. J. Brandon、M. D. Ehlers

  DOI：10.1124/jpet.115.229880

  日期：2016.1.15

  Traf2- and Nck-interacting kinase (TNIK) is a serine/threonine kinase highly expressed in the brain and enriched in the postsynaptic density of glutamatergic synapses in the mammalian brain. Accumulating genetic evidence and functional data have implicated TNIK as a risk factor for psychiatric disorders. However, the endogenous substrates of TNIK in neurons are unknown. Here, we describe a novel selective small molecule inhibitor of the TNIK kinase family. Using this inhibitor, we report the identification of endogenous neuronal TNIK substrates by immunoprecipitation with a phosphomotif antibody followed by mass spectrometry. Phosphorylation consensus sequences were defined by phosphopeptide sequence analysis. Among the identified substrates were members of the delta-catenin family including p120-catenin, δ -catenin, and armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF), each of which is linked to psychiatric or neurologic disorders. Using p120-catenin as a representative substrate, we show TNIK-induced p120-catenin phosphorylation in cells requires intact kinase activity and phosphorylation of TNIK at T181 and T187 in the activation loop. Addition of the small molecule TNIK inhibitor or knocking down TNIK by two shRNAs reduced endogenous p120-catenin phosphorylation in cells. Together, using a TNIK inhibitor and phosphomotif antibody, we identify endogenous substrates of TNIK in neurons, define consensus sequences for TNIK, and suggest signaling pathways by which TNIK influences synaptic development and function linked to psychiatric and neurologic disorders.

  Traf2和Nck相互作用激酶（TNIK）是一种丝氨酸/苏氨酸激酶，在哺乳动物大脑中高度表达，并富集于谷氨酸能突触的突触后密度中。不断积累的遗传证据和功能数据表明，TNIK 是精神疾病的一个风险因素。然而，TNIK 在神经元中的内源性底物尚不清楚。在这里，我们描述了 TNIK 激酶家族的一种新型选择性小分子抑制剂。利用这种抑制剂，我们报告了通过磷酸同源抗体免疫沉淀和质谱分析鉴定神经元内源性 TNIK 底物的结果。磷酸化共识序列是通过磷酸肽序列分析确定的。鉴定出的底物包括δ-catenin家族成员，包括p120-catenin、δ-catenin和犰狳重复基因缺失心面部综合征（ARVCF），其中每一种都与精神或神经系统疾病有关。以 p120-catenin 为代表底物，我们发现 TNIK 在细胞中诱导 p120-catenin 磷酸化需要完整的激酶活性以及 TNIK 在活化环中 T181 和 T187 处的磷酸化。加入小分子 TNIK 抑制剂或用两种 shRNA 敲除 TNIK 会降低细胞中内源性 p120-catenin 磷酸化。通过使用 TNIK 抑制剂和磷酸肌酸抗体，我们确定了 TNIK 在神经元中的内源性底物，定义了 TNIK 的共识序列，并提出了 TNIK 影响与精神和神经疾病相关的突触发育和功能的信号通路。
• Discovery of pyrazolo[3,4-d]pyrimidines as novel mitogen-activated protein kinase kinase 3 (MKK3) inhibitors
  作者：Jéssica E. Takarada、Micael R. Cunha、Vitor M. Almeida、Stanley N.S. Vasconcelos、André S. Santiago、Paulo H. Godoi、Anita Salmazo、Priscila Z. Ramos、Angela M. Fala、Lucas R. de Souza、Italo E.P. Da Silva、Mario H. Bengtson、Katlin B. Massirer、Rafael M. Couñago

  DOI：10.1016/j.bmc.2023.117561

  日期：2024.1

  optimization of inhibitors. In this study, we have developed a TR-FRET-based enzymatic assay for the detection of MKK3 activity in vitro and a BRET-based assay to assess ligand binding to this enzyme within intact human cells. These assays were instrumental in identifying hit compounds against MKK3 that share a common chemical scaffold, sourced from a library of bioactive kinase inhibitors. Initial hits

  双特异性蛋白激酶 MKK3 与肿瘤细胞增殖和存活有关，但其在癌症中的确切作用仍不确定。阐明激酶参与疾病生物学的关键一步是鉴定有效的细胞渗透性激酶抑制剂。目前，MKK3 缺乏用于这些目的的专用工具化合物，以及用于轻松筛选、鉴定和优化抑制剂的有效方法。在这项研究中，我们开发了一种基于 TR-FRET 的酶测定法，用于体外检测 MKK3 活性，并开发了一种基于 BRET 的测定法，用于评估完整人体细胞内配体与该酶的结合。这些测定有助于识别针对 MKK3 的命中化合物，这些化合物共享来自生物活性激酶抑制剂库的共同化学支架。随后通过合成新颖的类似物扩大了最初的成功。使用针对 MKK3 同源模型的分子动力学模拟，对所得构效关系 (SAR) 进行了合理化。我们期望我们的发现能够加速新型、有效、选择性和生物活性抑制剂的开发，从而促进 MKK3 在各种癌症中的作用的研究。
• [EN] 6-POSITION SUBSTITUTED DIHYDROBENZO[E][1,2,3]OXATHIAZINE 2,2-DIOXIDE COMPOUND, PREPARATION THEREFOR, AND USE THEREOF<br/>[FR] COMPOSÉ DE DIHYDROBENZO[E][1,2,3]OXATHIAZINE 2,2-DIOXYDE SUBSTITUÉ EN POSITION 6, SA PRÉPARATION ET SON UTILISATION<br/>[ZH] 6位取代二氢苯并[e][1,2,3]噁噻嗪2,2-二氧化类化合物及其制备与应用
  申请人：[en]HANGZHOU SEVENTH PEOPLE'S HOSPITAL;[zh]杭州市第七人民医院

  公开号：WO2024016826A1

  公开（公告）日：2024-01-25

  本发明属于有机合成医药领域，具体涉及6位取代3,4-二氢苯并[e][1,2,3]噁噻嗪2,2-二氧化类化合物，其通式如下： (I)该6位取代3,4-二氢苯并[e][1,2,3]噁噻嗪2,2-二氧化类化合物能够作为AMPA受体的正向变构调节剂，证实了该化合物能够正向调节AMPA受体，可使激动剂(如内源性神经递质谷氨酸)与受体结合后的构象更加稳定，从而降低受体失活率和抑制受体脱敏，使AMPA受体的功能得以增强。