4-(4-(3-(4-氯-3-(三氟甲基)苯基)脲啶)苯氧基)吡啶甲酸甲酯 | 573673-43-5

• 物质功能分类: 化学试剂 - 有机试剂 - 多环化合物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-(4-(3-(4-氯-3-(三氟甲基)苯基)脲啶)苯氧基)吡啶甲酸甲酯
• 英文名称: methyl 4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)picolinate
• 英文别名: methyl 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]pyridine-2-carboxylate
• CAS: 573673-43-5
• 化学式: C₂₁H₁₅ClF₃N₃O₄
• 分子量: 465.816
• InChiKey: MZUBVPBNBBPHLG-UHFFFAOYSA-N

物化性质

• 熔点：
  228-230 °C
• 沸点：
  494.4±45.0 °C(Predicted)
• 密度：
  1.469±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  89.6
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-(4-(3-(4-氯-3-(三氟甲基)苯基)脲啶)苯氧基)吡啶甲酸甲酯 在 一水合肼 、 三乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 氘代甲醇-d 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 1-(4-(2-(2-(4-phenylphenylacetyl)hydrazinocarbonyl)pyridine-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea
  参考文献：
  名称：

  Synthesis and in vitro cytotoxic activities of sorafenib derivatives

  摘要：

  A series of novel sorafenib derivatives have been designed and synthesized. The cytotoxic activities of these compounds were tested in three tumor cell lines. Most of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 0-20 mu mol/L. Some compounds demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines. Among them, compound 5g demonstrated significant inhibitory activity against A549, ACHN and MDA-MB-231 cell lines with IC50 values of 1.29, 1.99, 3.11 mu mol/L, respectively. (C) 2014 Zhi-Qiang Feng. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

  DOI：

  10.1016/j.cclet.2014.03.020
• 作为产物：
  描述：

  4-(4-氨基苯氧基)吡啶甲酸叔丁酯 在 三乙基硅烷 、 硫酸 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 35.0h， 生成 4-(4-(3-(4-氯-3-(三氟甲基)苯基)脲啶)苯氧基)吡啶甲酸甲酯
  参考文献：
  名称：

  METHOD AND PROCESS FOR PREPARATION AND PRODUCTION OF DEUTERATED OMEGA-DIPHENYLUREA

  摘要：

  揭示了制备和生产重氮化ω-二苯脲的方法和过程。特别是，揭示了一种可以抑制磷酸激酶的重氮化ω-二苯脲化合物以及N-(4-氯-3-(三氟甲基)苯基-N′-(4-(2-(N-d3-甲基氨基甲酰)-4-吡啶氧基)苯基)尿素的制备方法。所述的重氮化二苯脲化合物可用于治疗或预防肿瘤及相关疾病。

  公开号：

  US20130035492A1

文献信息

• Introduction of Mercaptoethyl at Sorafenib Pyridine-2-Amide Motif as a Potentially Effective Chain to Further get Sorafenib-PEG-DGL
  作者：Ke Wang、Kudelaidi Kuerbana、Qi Wan、Zhihui Yu、Li Ye、Ying Chen

  DOI：10.3390/molecules25030573

  日期：——

  The crystal structure of the sorafenib and B-RAF complex indicates that the binding cavity occupied by the pyridine-2-carboxamide in sorafenib has a large variable space, making it a reasonable modification site. In order to identify novel compounds with anti-cancer activity, better safety and polar groups for further application, five sorafenib analogs with new pyridine-2-amide side chains were designed and synthesized. Preliminary pharmacologic studies showed that these compounds displayed much lower toxicities than that of sorafenib. Among them, compound 10b bearing mercaptoethyl group kept relevant antiproliferation potency compared to sorafenib in Huh7 and Hela cell lines with values of IC50 58.79 and 63.67 μM, respectively. As a small molecule inhibitor targeting protein tyrosine kinases, thiol in compound 10b would be an active group to react with maleimide in a mild condition for forming nanoparticles Sorafenib-PEG-DGL, which could be developed as a delivery vehicle to improve the concentration of anti-tumor therapeutic agents in the target cancer tissue and reduce side effects in the next study.

  索拉非尼和B-RAF复合物的晶体结构表明，索拉非尼中吡啶-2-羧酰胺所占据的结合腔具有较大的可变空间，使其成为一个合理的修饰位点。为了寻找具有抗癌活性、更好的安全性和极性基团以供进一步应用的新化合物，设计并合成了五个具有新吡啶-2-酰胺侧链的索拉非尼类似物。初步药理研究显示，这些化合物的毒性明显低于索拉非尼。其中，携带巯基乙基基团的10b化合物在Huh7和Hela细胞系中与索拉非尼相比保持了相关的抗增殖活性，IC50值分别为58.79和63.67μM。作为靶向蛋白酪氨酸激酶的小分子抑制剂，10b化合物中的巯基可在温和条件下与马来酰亚胺发生反应，形成纳米粒子索拉非尼-PEG-DGL，可作为传递载体，提高抗肿瘤治疗药物在靶癌组织中的浓度，并在下一阶段研究中减少副作用。
• RAF KINASE INHIBITORS CONTAINING A ZINC BINDING MOIETY
  申请人：Cai Xiong

  公开号：US20080234332A1

  公开（公告）日：2008-09-25

  The present invention relates to Raf kinase inhibitors containing zinc-binding and their use in the treatment of Raf related diseases and disorders such as cancer. The said derivatives may further act as HDAC inhibitors.

  本发明涉及含有结合锌的Raf激酶抑制剂及其在治疗Raf相关疾病和紊乱（如癌症）中的应用。所述衍生物还可能作为HDAC抑制剂。
• [EN] METHOD AND PROCESS FOR PREPARATION AND PRODUCTION OF DEUTERATED O-DIPHENYLUREA<br/>[FR] MÉTHODE ET PROCÉDÉS DE PRÉPARATION ET DE PRODUCTION DE O-DIPHÉNYLURÉE DEUTÉRÉE
  申请人：SUZHOU ZELGEN BIOPHARMACEUTICAL CO LTD

  公开号：WO2011113367A1

  公开（公告）日：2011-09-22

  Methods and processes for preparation and production of deuterated ω-diphenylure are disclosed. Especially, a kind of deuterated ω-diphenylurea compounds which can inhibit phosphokinase and the preparation method of N-(4-chloro-3-(trifluoromethyl)phenyl)-N'-(4-(2-(N-1',1',1'-d3-methylcarbamoyl)-4-pyridinyloxy)phenyl)urea are disclosed. The said deuterated diphenylurea compounds can be used for treating or preventing tumors and relative diseases.

  本发明公开了制备和生产氘代ω-二苯基脲的方法和过程。特别是，公开了一种可以抑制磷酸激酶的氘代ω-二苯基脲化合物以及N-(4-氯-3-(三氟甲基)苯基)-N'-(4-(2-(N-1'，1'，1'-d3-甲基氨基甲酰)-4-吡啶氧基)苯基)脲的制备方法。所述的氘代二苯基脲化合物可用于治疗或预防肿瘤及相关疾病。
• Substituted pyridine derivatives useful in the treatment of cancer and other disorders
  申请人：——

  公开号：US20040229937A1

  公开（公告）日：2004-11-18

  This invention relates to novel diaryl ureas, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for treating hyper-proliferative and angiogenesis disorders, as a sole agent or in combination with cytotoxic therapies.

  本发明涉及新型二芳基脲、含有这些化合物的制药组合物以及将这些化合物或组合物用于治疗高增殖和血管生成障碍的用途，作为唯一的药物或与细胞毒性治疗联合使用。
• Multi-Functional Small Molecules as Anti-Proliferative Agents
  申请人：Cai Xiong

  公开号：US20080221132A1

  公开（公告）日：2008-09-11

  The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.

  本发明涉及一种新型选择性抑制多种细胞或分子靶点的组合物、方法和应用。更具体地说，本发明涉及多功能小分子，其中一种功能能够抑制组蛋白去乙酰化酶（HDAC），另一种功能能够抑制与异常细胞增殖、分化或存活有关的不同细胞或分子途径。