1-(2-fluoro-5-(trifluoromethyl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea | 796967-62-9

• 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: 1-(2-fluoro-5-(trifluoromethyl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea
• 英文别名: 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea
• CAS: 796967-62-9
• 化学式: C₂₀H₂₁BF₄N₂O₃
• 分子量: 424.203
• InChiKey: DBYMXBDSVQKVEQ-UHFFFAOYSA-N

物化性质

• 沸点：
  400.0±42.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.79
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(2-fluoro-5-(trifluoromethyl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea 在 四(三苯基膦)钯 potassium fluoride 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.17h， 生成 3-{4-[3-(2-Fluoro-5-trifluoromethylphenyl)-ureido]phenyl}-7-nitro-1H-indole-2-carboxamide
  参考文献：
  名称：

  Substituted Indoles, Compositions Containing Them, Method for the Production Thereof and Their Use

  摘要：

  式(I)的化合物：其中R1、R5、R6、R7、Ar、L、A和Q如描述中所定义，并其盐，含有它们的组合物，制备它们的方法，以及它们作为药物的用途，特别是作为抗癌剂。

  公开号：

  US20070259910A1
• 作为产物：
  描述：

  4-异氰酰苯基硼酸频哪醇酯 、 2-氟-5-三氟甲基苯胺 以 二氯甲烷 为溶剂， 生成 1-(2-fluoro-5-(trifluoromethyl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea
  参考文献：
  名称：

  Discovery of N-(4-(3-Amino-1H-indazol-4-yl)phenyl)-N‘-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-Aminoindazole-Based Orally Active Multitargeted Receptor Tyrosine Kinase Inhibitor

  摘要：

  In our continued efforts to search for potent and novel receptor tyrosine kinase (RTK) inhibitors as potential anticancer agents, we discovered, through a structure-based design, that 3-aminoindazole could serve as an efficient hinge-binding template for kinase inhibitors. By incorporating an N,N'-diaryl urea moiety at the C4-position of 3-aminodazole, a series of RTK inhibitors were generated, which potently inhibited the tyrosine kinase activity of the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor families. A number of compounds with potent oral activity were identified by utilizing an estradiol-induced mouse uterine edema model and an HT1080 human fibrosarcoma xenograft tumor model. In particular, compound 17p (ABT-869) was found to possess favorable pharmacokinetic profiles across different species and display significant tumor growth inhibition in multiple preclinical animal models.

  DOI：

  10.1021/jm061280h

文献信息

• Discovery of 7-Oxo-2,4,5,7-tetrahydro-6<i>H</i>-pyrazolo[3,4-<i>c</i>]pyridine Derivatives as Potent, Orally Available, and Brain-Penetrating Receptor Interacting Protein 1 (RIP1) Kinase Inhibitors: Analysis of Structure–Kinetic Relationships
  作者：Masato Yoshikawa、Morihisa Saitoh、Taisuke Katoh、Tomohiro Seki、Simone V. Bigi、Yuji Shimizu、Tsuyoshi Ishii、Takuro Okai、Masako Kuno、Harumi Hattori、Etsuro Watanabe、Kumar S. Saikatendu、Hua Zou、Masanori Nakakariya、Takayuki Tatamiya、Yoshihisa Nakada、Takatoshi Yogo

  DOI：10.1021/acs.jmedchem.7b01647

  日期：2018.3.22

  highly potent, orally available, and brain-penetrating RIP1 kinase inhibitor with excellent PK profiles. Compound 22 significantly suppressed necroptotic cell death both in mouse and human cells. Oral administration of 22 (10 mg/kg, bid) attenuated disease progression in the mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). Moreover, analysis of structure–kinetic

  我们报告发现7-oxo-2,4,5,7-四氢-6 H-吡唑并[3,4- c ]吡啶衍生物作为一种新型的受体相互作用蛋白1（RIP1）激酶抑制剂。在HTS命中10与RIP1激酶的GSK2982772（6）之间的叠加研究的基础上，我们设计并合成了具有中度RIP1激酶抑制活性和P-gp介导外排的新型RIP1激酶抑制剂11。核心结构的优化和利用SBDD方法探索适当取代基的发现导致发现22，一种具有出色PK谱的高效，口服，可穿透脑的RIP1激酶抑制剂。化合物22显着抑制小鼠和人类细胞中的坏死性细胞死亡。在多发性硬化症（MS）小鼠实验性自身免疫性脑脊髓炎（EAE）模型中，口服22（10 mg / kg，bid）的剂量可减轻疾病的进展。此外，还讨论了我们新化学系列的结构动力学关系（SKR）分析。
• SUBSTITUTED PYRAZOLOPYRIDINES, COMPOSITIONS CONTAINING THEM, METHOD FOR THE PRODUCTION THEREOF, AND THEIR USE
  申请人：RONAN Baptiste

  公开号：US20080039491A1

  公开（公告）日：2008-02-14

  The disclosure relates to substituted pyrazolo-pyridines, compositions containing them, methods for the production thereof, and to their use as medicaments, in particular, as anticancer agents.

  该公开涉及取代的吡唑啉-吡啶类化合物，含有它们的组合物，其生产方法，以及它们作为药物的用途，特别是作为抗癌药物。
• Sulfonamido-macrocycles as Tie2 inhibitors and the salts thereof, a pharmaceutical composition comprising these compounds, the method of preparing and the use thereof
  申请人：Kettschau Georg

  公开号：US20060194823A1

  公开（公告）日：2006-08-31

  The invention relates to sulfonamido-macrocycles according to the general Formula I and the salts thereof, to pharmaceutical compositions comprising the sulfonamido-macrocycles and to a method of preparing the sulfonamido-macrocycles as well as the use thereof for manufacturing a pharmaceutical composition for the treatment of diseases of dysregulated vascular growth or of diseases which are accompanied with dysregulated vascular growth, wherein the compounds effectively interfere with angiopoietin and therefore influence Tie2 signalling. wherein R 1 , R 2 , R 4 , A, X, Y, Z and m have the meaning as given in the specification and the claims.

  该发明涉及一般式I所示的磺胺基-大环化合物及其盐，包括含有磺胺基-大环化合物的药物组合物，以及制备磺胺基-大环化合物的方法，以及用于制造治疗血管生长失调疾病或伴随血管生长失调的疾病的药物组合物的用途，其中这些化合物有效地干扰血管生成素，从而影响Tie2信号传导，其中R1、R2、R4、A、X、Y、Z和m的含义如规范和权利要求中所示。
• Sulfonamido-macrocycles as Tie2 inhibitors
  申请人：Schering Aktiengesellschaft

  公开号：EP1674469A1

  公开（公告）日：2006-06-28

  The invention relates to sulfonamido-macrocycles according to the general Formula I and the salts thereof, to pharmaceutical compositions comprising the sulfonamido-macrocycles and to a method of preparing the sulfonamido-macrocycles as well as the use thereof for manufacturing a pharmaceutical composition for the treatment of diseases of dysregulated vascular growth or of diseases which are accompanied with dysregulated vascular growth, wherein the compounds effectively interfere with angiopoietin and therefore influence Tie2 signalling. wherein R1, R2, R4, A, X, Y, Z and m have the meaning as given in the specification and the claims.

  该发明涉及根据一般式I和其盐的磺胺基大环化合物，包括含有磺胺基大环化合物的药物组合物，以及制备磺胺基大环化合物的方法以及用于制造治疗血管生长失调疾病或伴随血管生长失调的疾病的药物组合物的用途，其中这些化合物有效干扰血管生成素，从而影响Tie2信号传导，其中R1、R2、R4、A、X、Y、Z和m的含义如规范和权利要求中所述。
• 7-Substituted Aza-Indazoles, Compositions Containing Same, Production Method and Use Thereof
  申请人：BJERGARDE Kirsten

  公开号：US20080182844A1

  公开（公告）日：2008-07-31

  The disclosure relates to compounds of formula (I): which modulate the activity of proteins, particularly kinases, and to compositions containing the same, and to the use thereof as medicaments, in particular as anticancer agents.

  本发明涉及式(I)的化合物，其调节蛋白质的活性，特别是激酶的活性，以及含有它们的组合物，以及将其用作药物，特别是抗癌剂。