3-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N-methylbenzamide

• 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: 3-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N-methylbenzamide
• 英文别名: sorafenib；nevaxar；3-[4-[[[4-chloro-3-(trifluoromethyl)anilino]-oxomethyl]amino]phenoxy]-N-methylbenzamide；3-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-N-methylbenzamide
• 化学式: C₂₂H₁₇ClF₃N₃O₃
• 分子量: 463.843
• InChiKey: CGFGJVMEGKQFPL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  79.5
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N-methylbenzamide 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 10.0h， 生成 3-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)benzoic acid
  参考文献：
  名称：

  基于生物正交反应和可释放二硫键的成像与治疗一体化双功能分子的发现

  摘要：

  传统荧光探针在活细胞中的应用受到过度荧光干扰、选择性降低和渗透性差的限制。在这里，我们描述了一种方便的解决方案，用于克服基于生物正交反应和可释放接头的上述限制，这些接头为成像和治疗整合提供双功能分子。为了减少过量荧光部分的干扰，应用生物正交反应来激活没有荧光团的活性母体药物的荧光。此外，将二硫键作为可释放的接头掺入。在对靶蛋白进行成像后，新产生的荧光团可以根据肿瘤的高度还原条件从活性药物中释放出来。因此，这些双功能分子的治疗活性与母体药物相当。这些新型成像和治疗整合分子可用于实现成像辅助诊断和对癌细胞进行有效的实时监测。我们的研究结果有望在临床上实现高效和特异性的成像和实时体内预后监测。

  DOI：

  10.1021/acs.bioconjchem.2c00133
• 作为产物：
  描述：

  3-羟基苯甲酸乙酯 在 氯化亚砜 、 lithium hydroxide monohydrate 、 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 3-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N-methylbenzamide
  参考文献：
  名称：

  Life Beyond Kinases: Structure-Based Discovery of Sorafenib as Nanomolar Antagonist of 5-HT Receptors

  摘要：

  Of great interest in recent years has been computationally predicting the novel polypharmacology of drug molecules. Here, we applied an "induced-fit" protocol to improve the homology models of 5-HT2A receptor, and we assessed the quality of these models in retrospective virtual screening. Subsequently, we computationally screened the FDA approved drug molecules against the best induced-fit 5-HT2A models and chose six top scoring hits for experimental assays. Surprisingly, one well-known kinase inhibitor, sorafenib, has shown unexpected promiscuous 5-HTRs binding affinities, K-i = 1959, 56, and 417 nM against 5-HT2A, 5-HT2B, and 5-HT2C, respectively. Our preliminary SAR exploration supports the predicted binding mode and further suggests sorafenib to be a novel lead compound for 5HTR ligand discovery. Although it has been well-known that sorafenib produces anticancer effects through targeting multiple kinases, carefully designed experimental studies are desirable to fully understand whether its "off-target" 5-HTR binding activities contribute to its therapeutic efficacy or otherwise undesirable side effects.

  DOI：

  10.1021/jm300338m

文献信息

• TREATMENT OF CANCER WITH SORAFENIB
  申请人：Wilhelm Scott

  公开号：US20090215835A1

  公开（公告）日：2009-08-27

  The present invention provides compositions and methods for treating specific cancers with effective amounts of sorafenib.

  本发明提供了使用有效剂量的索拉非尼治疗特定癌症的组合物和方法。
• ANTI-CANCER PHOSPHONATE ANALOGS
  申请人：Boojamra Constantine G.

  公开号：US20100022467A1

  公开（公告）日：2010-01-28

  The invention is related to phosphorus substituted anti-cancer compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

  本发明涉及磷取代的抗癌化合物、含有这些化合物的组合物以及包括给予这些化合物的治疗方法，还涉及用于制备这些化合物的过程和中间体。
• Process for the Preparation of 4-Carbonyl)Amino]Phenoxy}-N-Methylpyridine-2-Carboxamide
  申请人：Logers Michael

  公开号：US20080262236A1

  公开（公告）日：2008-10-23

  The present invention relates to a process for preparing 4-4-[([4-chloro-3-(trifluoro-methyl)phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboxamide and its tosylate salt.

  本发明涉及一种制备4-4-[([4-氯-3-(三氟甲基)苯基]氨基}羰基)氨基]苯氧基}-N-甲基吡啶-2-甲酸酰胺及其对甲苯磺酸盐的过程。
• Heteroarylphenylurea Derivative
  申请人：Oikawa Nobuhiro

  公开号：US20080119466A1

  公开（公告）日：2008-05-22

  The present invention provides a compound represented by the formula (1): wherein R 1 , R 2 and R 5 are each independently selected from a hydrogen atom, a halogen atom, a C 1 -C 6 alkyl is substituted with a halogen atom and the like; R 3 and R 4 are each independently selected from a hydrogen atom, a halogen atom, a substituted C 1 -C 6 alkyl group and the like; R 6 and R 7 are each independently selected from a hydrogen atom and a halogen atom; Z 1 and Z 2 are each independently selected from a hydrogen atom, a hydroxyl group and —O(CHR 11 )OC(═O)R 12 ; Q is a group of the formula: (wherein G 1 is C—Y 2 or N; a ring A is a benzene ring or a 5- to 6-membered unsaturated heterocycle) a pharmaceutically acceptable salt thereof or a prodrug thereof.

  本发明提供了一种由式（1）表示的化合物：其中，R1、R2和R5分别独立地选自氢原子、卤原子、C1-C6烷基被卤原子等取代基；R3和R4分别独立地选自氢原子、卤原子、取代的C1-C6烷基等基团；R6和R7分别独立地选自氢原子和卤原子；Z1和Z2分别独立地选自氢原子、羟基和—O（CHR11）OC（═O）R12；Q是下式的基团：（其中，G1是C—Y2或N；环A是苯环或5-至6-成员的不饱和杂环）；其药学上可接受的盐或前药。
• ARYL NAPHTHYL METHANONE OXIME(S) AND PROCESS FOR PREPARATION THEREOF
  申请人：COUNCIL OF SCIENTIFIC & INDUSTRIAL rESEARCH

  公开号：US20160304442A1

  公开（公告）日：2016-10-20

  The present invention relates to substituted aryl naphthyl methanone oximes of general formula (I), their process for preparation and their derivatives, salts, pharmaceutical composition thereof and their use in treatment of chronic myelogenous leukemia, acute myelogenous leukemia, lymphoma, multiple myeloma, solid tumor forming cell- lines including such as breast cancer, endometrial cancer colon cancer, prostate cancer and killing of drug resistant cancer stem cells, as subject in need thereof.