cis-4-{4-[3-(4-chloro-3-trifluoromethylphenyl)ureido]cyclohexyloxy}pyridine-2-carboxylic acid methylamide | 1394012-02-2

• 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: cis-4-{4-[3-(4-chloro-3-trifluoromethylphenyl)ureido]cyclohexyloxy}pyridine-2-carboxylic acid methylamide
• CAS: 1394012-02-2
• 化学式: C₂₁H₂₂ClF₃N₄O₃
• 分子量: 470.879
• InChiKey: VZOUKWZMPPMODY-XBXGTLAGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.63
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.35
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  2-(trans-4-Hydroxycyclohexyl)isoindoline-1,3-dione 在 偶氮二甲酸二异丙酯 、 potassium tert-butylate 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 、 三苯基膦 、 sodium hydroxide 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 cis-4-{4-[3-(4-chloro-3-trifluoromethylphenyl)ureido]cyclohexyloxy}pyridine-2-carboxylic acid methylamide
  参考文献：
  名称：

  Synthesis and biological evaluation of sorafenib- and regorafenib-like sEH inhibitors

  摘要：

  To reduce the pro-angiogenic effects of sEH inhibition, a structure-activity relationship (SAR) study was performed by incorporating structural features of the anti-angiogenic multi-kinase inhibitor sorafenib into soluble epoxide hydrolase (sEH) inhibitors. The structural modifications of this series of molecules enabled the altering of selectivity towards the pro-angiogenic kinases C-RAF and vascular endothelial growth factor receptor-2 (VEGFR-2), while retaining their sEH inhibition. As a result, sEH inhibitors with greater potency against C-RAF and VEGFR-2 were obtained. Compound 4 (t-CUPM) possesses inhibition potency higher than sorafenib towards sEH but similar against C-RAF and VEGFR-2. Compound 7 (t-CUCB) selectively inhibits sEH, while inhibiting HUVEC cell proliferation, a potential anti-angiogenic property, without liver cancer cell cytotoxicity. The data presented suggest a potential rational approach to control the angiogenic responses stemming from sEH inhibition. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.05.011

文献信息

• [EN] SORAFENIB DERIVATIVES AS sEH INHIBITORS<br/>[FR] DÉRIVÉS DE SORAFÉNIB UTILISÉS EN TANT QU'INHIBITEURS DE LA SEH
  申请人：UNIV CALIFORNIA

  公开号：WO2012112570A1

  公开（公告）日：2012-08-23

  The present invention provides compounds for the inhibition of soluble epoxide hydrolase and associated disease conditions.

  本发明提供了用于抑制可溶性环氧化物水解酶及相关疾病状况的化合物。
• SORAFENIB DERIVATIVES AS SEH INHIBITORS
  申请人：Hammock Bruce D.

  公开号：US20140088156A1

  公开（公告）日：2014-03-27

  The present invention provides compounds for the inhibition of soluble epoxide hydrolase and associated disease conditions.

  本发明提供了用于抑制可溶性环氧酰胺酶及相关疾病状况的化合物。
• Sorafenib derivatives as p21 inhibitors
  申请人：The Regents of the University of California

  公开号：US10449182B2

  公开（公告）日：2019-10-22

  The present invention provides sorafenib analogs for use in a method of treating a disease mediated by p21, said method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I. The present invention also provides methods of inhibiting p21 in a cell comprising contacting the cell with an effective amount of a compound of formula I.

  本发明提供了用于治疗由p21介导的疾病的方法中的索拉非尼类似物，所述方法包括向有需要的受试者施用治疗有效量的式I化合物。本发明还提供了抑制细胞中p21的方法，包括使细胞与有效量的式I化合物接触。
• SORAFENIB DERIVATIVES AS sEH INHIBITORS
  申请人：The Regents of the University of California

  公开号：EP2675274B1

  公开（公告）日：2017-05-03
• SORAFENIB DERIVATIVES AS P21 INHIBITORS
  申请人：The Regents of the University of California

  公开号：US20150132408A1

  公开（公告）日：2015-05-14

  The present invention provides sorafenib analogs for use in a method of treating a disease mediated by p21, said method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I. The present invention also provides methods of inhibiting p21 in a cell comprising contacting the cell with an effective amount of a compound of formula I.