1-(2-aminoethyl)-3-(3,5-bis(trifluoromethyl)phenyl)urea | 1360816-01-8

• 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: 1-(2-aminoethyl)-3-(3,5-bis(trifluoromethyl)phenyl)urea
• CAS: 1360816-01-8
• 化学式: C₁₁H₁₁F₆N₃O
• 分子量: 315.218
• InChiKey: SRYLBZJEMULZMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  67.15
• 氢给体数：
  3.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  N⁶-(2-chloro-6-methylpyrimidin-4-yl)-2-methylquinoline-4,6-diamine 、 1-(2-aminoethyl)-3-(3,5-bis(trifluoromethyl)phenyl)urea 在 N,N-二异丙基乙胺 作用下， 反应 0.25h， 以22%的产率得到1-(2-((4-((4-amino-2-methylquinolin-6-yl)amino)-6-methylpyrimidin-2-yl)amino)ethyl)-3-(3,5-bis(trifluoromethyl)phenyl)urea
  参考文献：
  名称：

  嘧啶基氨基喹啉衍生物作为DOT1L抑制剂的设计，合成及抗白血病细胞增殖活性

  摘要：

  通过在DOT1L铅抑制剂3a上进行结构修饰，设计并合成了一系列含有氨基侧链的新型嘧啶基氨基喹啉衍生物8（ai）和9（ai），以及双氨基喹啉类似物3（be）。已经评估了所有化合物的DOT1L抑制活性。结果表明，大多数化合物具有很强的抗DOT1L活性。化合物3e，8h和9e是IC 50每种类别中最有潜力的化合物值分别为1.06±0.35μM，5.72±1.56μM和3.55±1.28μM。此类抑制剂通过基于表面等离振子共振（SPR）的结合测定表达了与DOT1L的显着结合相互作用。分子对接实验的结果表明它们可以占据DOT1L的SAM结合口袋。与3a和3e的化合物相比，化合物8h和9e对MLL重排的MV4-11细胞和非MLL重排的Kasumi-1细胞均表现出更好的抑制活性，但选择性较差。，这表明引入氨基侧链可能有助于其抗白血病细胞的增殖活性，这可能是由于脂肪溶解度的提高所致。此外，在qRT-PCR

  DOI：

  10.1016/j.bioorg.2018.07.022
• 作为产物：
  描述：

  在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 1-(2-aminoethyl)-3-(3,5-bis(trifluoromethyl)phenyl)urea
  参考文献：
  名称：

  新型6-(4-氟苯基)-5-(2-取代嘧啶-4-基)咪唑并[2,1-b]噻唑衍生物的合成及其对黑色素瘤细胞系的抗增殖活性

  摘要：

  描述了一系列新的嘧啶基-咪唑(2,1-b)噻唑衍生物的合成。测试了它们对 A375 人黑色素瘤细胞系的抗增殖活性，并研究了取代基对嘧啶环侧链的影响。生物学结果表明，与索拉非尼相比，大多数新合成的化合物对 A375 具有中等活性。在所有这些衍生物中，环状磺酰胺衍生物 IIIa、IIIb 和 IIIe 对 A375 人黑色素瘤细胞系显示出最有效的抗增殖活性。化合物 IIIa、b 的 IC50 值为纳摩尔级。此外，与索拉非尼 (IC50 = 5.6 µM) 相比，化合物 IIIe (IC50 = 1.9 µM) 也显示出更有效的抗增殖活性。

  DOI：

  10.5012/bkcs.2010.31.10.2854

文献信息

• Synthesis and plasma pharmacokinetics in CD-1 mice of a 18β-glycyrrhetinic acid derivative displaying anti-cancer activity
  作者：Benjamin Lallemand、Moustapha Ouedraogo、Nathalie Wauthoz、Touria Lamkami、Veronique Mathieu、Ivan Jabin、Karim Amighi、Robert Kiss、Jacques Dubois、Jonathan Goole

  DOI：10.1111/j.2042-7158.2012.01603.x

  日期：2013.1.29

  The plasma pharmacokinetic profile in CD-1 mice of a novel 18β-glycyrrhetinic acid (GA) derivative, which displays in vitro anti-cancer activity, was assessed.

  This study involved an original one-step synthesis of N-(2-3-[3,5-bis(trifluoromethyl)phenyl]ureido}ethyl)-glycyrrhetinamide, (2) a compound that displays marked anti-proteasome and anti-kinase activity. The bioselectivity profile of 2 on human normal NHDF fibroblasts vs human U373 glioblastoma cells was assessed. Maximal tolerated dose (MTD) profiling of 2 was carried out in CD1 mice, and its serum pharmacokinetics were profiled using an acute intravenous administration of 40 mg/kg body weight.

  Compound 2 displayed IC50  in vitro growth inhibitory concentrations of 29 and 8 μm on NHDF fibroblasts and U373 glioblastoma cells, respectively, thus a bioselectivity index of ∼4. The intravenous pharmacokinetic parameters revealed that 2 was rapidly distributed (t1/2dist of ∼3 min) but slowly eliminated (t1/2elim = ∼77 min).

  This study describes an original and reliable nanoemulsion of a GA derivative with both anti-proteasome and anti-kinase properties and that should be further tested in vivo using various human xenograft or murine syngeneic tumour models with both single and chronic intravenous administration.

  评估一种新型18β-甘草酸（GA）衍生物在CD-1小鼠中的血浆药代动力学特征，该衍生物在体外显示抗癌活性。

  本研究涉及一种原始的N-(2-3-[3,5-双三氟甲基苯基]脲基}乙基)-甘草酸酰胺（2）的一步合成，该化合物显示出明显的抗蛋白酶和抗激酶活性。评估2在人正常NHDF成纤维细胞与人U373胶质母细胞瘤细胞上的生物选择性特征。在CD1小鼠中进行2的最大耐受剂量（MTD）分析，并使用40 mg/kg体重的急性静脉给药分析其血清药代动力学。

  化合物2在NHDF成纤维细胞和U373胶质母细胞瘤细胞上显示出IC50体外生长抑制浓度分别为29和8 μm，因此生物选择性指数约为4。静脉药代动力学参数显示，2迅速分布（t1/2dist约为3分钟），但缓慢消除（t1/2elim = 约77分钟）。

  本研究描述了一种原始可靠的GA衍生物纳米乳剂，具有抗蛋白酶和抗激酶特性，应进一步在体内使用各种人源异种移植物或小鼠同种肿瘤模型中进行单次和慢性静脉给药的测试。

• New imidazo[2,1-b]thiazole derivatives: Synthesis, in vitro anticancer evaluation, and in silico studies
  作者：Jin-Hun Park、Mohammed I. El-Gamal、Yong Sup Lee、Chang-Hyun Oh

  DOI：10.1016/j.ejmech.2011.08.024

  日期：2011.12

  A series of 18 new imidazo[2,1-b]thiazole derivatives was synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-60 cell line panel were tested. Compounds 15, 16, 18, 22, 26-28, and 31 showed superior potency against A375P to sorafenib. In addition, compounds 26 and 27 showed selectivity toward melanoma cell lines than for other cancer types. Both compounds exerted sub-micromolar IC50 values over 7 (including A375P) and 6 melanoma cell lines, respectively. in silico studies are also reported. ADME profiling, in silico toxicity, drug-likeness, and drug-score data of compounds 26 and 27 are promising. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Imidazothiazole-based potent inhibitors of V600E-B-RAF kinase with promising anti-melanoma activity: biological and computational studies
  作者：Hanan S. Anbar、Mohammed I. El-Gamal、Hamadeh Tarazi、Bong S. Lee、Hong R. Jeon、Dow Kwon、Chang-Hyun Oh

  DOI：10.1080/14756366.2020.1819260

  日期：2020.1.1

  A series of imidazothiazole derivatives possessing potential activity against melanoma cells were investigated for molecular mechanism of action. The target compounds were tested against V600E-B-RAF and RAF1 kinases. Compound1zbis the most potent against both kinases with IC(50)values 0.978 and 8.2 nM, respectively. It showed relative selectivity against V600E mutant B-RAF kinase. Compound1zbwas also tested against four melanoma cell lines and exerted superior potency (IC(50)0.18-0.59 mu M) compared to the reference standard drug, sorafenib (IC(50)1.95-5.45 mu M). Compound1zbdemonstrated also prominent selectivity towards melanoma cells than normal skin cells. It was further tested in whole-cell kinase assay and showed in-cell V600E-B-RAF kinase inhibition with IC(50)of 0.19 mu M. Compound1zbinduces apoptosis not necrosis in the most sensitive melanoma cell line, UACC-62. Furthermore, molecular dynamic and 3D-QSAR studies were done to investigate the binding mode and understand the pharmacophoric features of this series of compounds.