5-溴-3,4-二氟-2-(4-碘-2-甲基苯胺基)苯甲酸 | 212628-46-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-溴-3,4-二氟-2-(4-碘-2-甲基苯胺基)苯甲酸
• 英文名称: 5-bromo-3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid
• 英文别名: 5-bromo-3,4-difluoro-2-(4-iodo-2-methylanilino)benzoic acid
• CAS: 212628-46-1
• 化学式: C₁₄H₉BrF₂INO₂
• 分子量: 468.036
• InChiKey: IHCADDZQYYEXFH-UHFFFAOYSA-N

物化性质

• 沸点：
  429.4±45.0 °C(Predicted)
• 密度：
  2.026±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-氯苯甲酰乙腈 、 5-溴-3,4-二氟-2-(4-碘-2-甲基苯胺基)苯甲酸 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 以61%的产率得到5-bromo-3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-N-methoxy-benzamide
  参考文献：
  名称：

  The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901

  摘要：

  A novel series of benzhydroxamate esters derived from their precursor anthranilic acids have been prepared and have been identified as potent MEK inhibitors. 2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide, CI-1040, was the first MEK inhibitor to demonstrate in vivo activity in preclinical animal models and subsequently became the first MEK inhibitor to enter clinical trial. CI-1040 suffered however from poor exposure due to its poor solubility and rapid clearance, and as a result, development of the compound was terminated. Optimization of the diphenylamine core and modi. cation of the hydroxamate side chain for cell potency, solubility, and exposure with oral delivery resulted in the discovery of the clinical candidate N-(2,3-dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide PD 0325901. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.054
• 作为产物：
  描述：

  4-碘-2-甲基苯胺 、 5-溴-2,3,4-三氟苯甲酸 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 以89%的产率得到5-溴-3,4-二氟-2-(4-碘-2-甲基苯胺基)苯甲酸
  参考文献：
  名称：

  2-(N-苯基氨基)-苯甲酸的简单高效合成

  摘要：

  摘要 以 2-氟苯甲酸和苯胺为起始原料，提出了一种合成 2-(N-苯基氨基)苯甲酸的新方法。描述了几个实验条件以及影响反应结果的因素。

  DOI：

  10.1081/scc-120002125

文献信息

• Oxygenated esters of 4-lodo phenylamino benzhydroxamic acids
  申请人：——

  公开号：US20040054172A1

  公开（公告）日：2004-03-18

  The present invention relates to oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof. The present invention also relates to crystaline forms of oxygenated esters of 4-iodophenylamino benzhydroxamic acid derivatives, pharmaceutical compositions and methods of use thereof.

  本发明涉及氧化酯化的4-碘苯胺基苯基羟肟酸衍生物，以及其药物组合物和使用方法。本发明还涉及氧化酯化的4-碘苯胺基苯基羟肟酸衍生物的晶体形式，药物组合物和使用方法。
• Method of treating or preventing septic shock by administering a MEK inhibitor
  申请人：Warner-Lambert Company

  公开号：US06251943B1

  公开（公告）日：2001-06-26

  The present invention provides a method for treating or preventing septic shock. Specifically, the present invention provides a method of treating or preventing septic shock by administering to a patient a MEK inhibitor.

  本发明提供了一种治疗或预防感染性休克的方法。具体地，本发明提供了一种通过给患者注射MEK抑制剂来治疗或预防感染性休克的方法。
• Treatment of asthma with MEK inhibitors
  申请人：Warner-Lambert Company

  公开号：US06696440B1

  公开（公告）日：2004-02-24

  This invention provides a method of preventing or treating asthma by administering to a patient in need of treatment an effective amount of a selective MEK inhibitor, especially a phenyl amine of Formula I and II:

  该发明提供了一种通过向需要治疗的患者施用有效量的选择性MEK抑制剂来预防或治疗哮喘的方法，特别是公式I和II的苯胺类化合物。
• 4-bromo or 4-iodo phenylamino benzhydroxamic acid derivatives and their use as MEK inhibitors
  申请人：——

  公开号：US20030078428A1

  公开（公告）日：2003-04-24

  Phenylamino benzhydroxamic acid derivatives of formula (I) where R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are hydrogen or substituent groups such as alkyl, and where R 7 is hydrogen or an organic radical, are potent inhibitors of MEK and, as such, are effective in treating cancer and other proliferative diseases such as psoriasis and restenosis.

  苯胺基苯基羟羟肟酸衍生物的化学式（I），其中R1、R2、R3、R4、R5和R6为氢或取代基，如烷基，R7为氢或有机基团，是MEK的有效抑制剂，因此在治疗癌症和其他增殖性疾病（如牛皮癣和再狭窄）方面具有良好效果。
• Combination chemotherapy
  申请人：——

  公开号：US20040171632A1

  公开（公告）日：2004-09-02

  Mitotic inhibitors such as paclitaxel have improved antitumor activity when used in combination with a selective MEK inhibitor, especially a phenyl amine compound of Formula I and II: 1

  有丝分裂抑制剂如紫杉醇在与选择性MEK抑制剂结合使用时，特别是Formula I和II的苯胺化合物，已提高抗肿瘤活性。