4-fluoro-2-(4-iodo-2-methyl-phenylamino)-N-methoxy-benzamide

• 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: 4-fluoro-2-(4-iodo-2-methyl-phenylamino)-N-methoxy-benzamide
• 英文别名: 4-Fluoro-2-(4-iodo-2-methyl-phenylamino)-N-(methoxy)-benzamide；4-Fluoro-2-[(4-iodo-2-methylphenyl)amino]-N-methoxybenzamid；4-fluoro-2-(4-iodo-2-methylanilino)-N-methoxybenzamide
• 化学式: C₁₅H₁₄FIN₂O₂
• 分子量: 400.191
• InChiKey: PEZQORQECWUYJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-氯苯甲酰乙腈 、 4-fluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid 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50%的产率得到4-fluoro-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

文献信息

• 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。
• Synergistic methods and compositions for treating cancer
  申请人：——

  公开号：US20040209930A1

  公开（公告）日：2004-10-21

  Combination therapies using IGF1R inhibitors in combination with additional kinase inhibitors are described for the synergistic treatment of cancer.

  描述了使用IGF1R抑制剂与其他激酶抑制剂结合的联合疗法，用于癌症的协同治疗。
• [EN] 4-BROMO OR 4-IODO PHENYLAMINO BENZHYDROXAMIC ACID DERIVATIVES AND THEIR USE AS MEK INHIBITORS<br/>[FR] DERIVES D'ACIDE BENZHYDROXAMIQUE PHENYLAMINO 4-BROMO OU 4-IODO ET UTILISATION DE CES DERNIERS EN TANT QU'INHIBITEURS DE MEK
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1999001426A1

  公开（公告）日：1999-01-14

  (EN) Phenylamino benzhydroxamic acid derivatives of formula (I) where R1, R2, R3, R4, R5, and R6 are hydrogen or substituent groups such as alkyl, and where R7 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.(FR) On décrit des dérivés d'acide benzhydroxamique phénylamino de formule (I). Dans la formule R1, R2, R3, R4, R5 et R6 représentent hydrogène ou des groupes substituants tels que alkyle; R7 représentant hydrogène ou un radical organique. Ces dérivés sont de puissants inhibiteurs de MEK et en tant que tels ils sont efficaces dans le traitement du cancer et d'autres maladies proliférantes telles que le psoriasis et la resténose.

  Phenylamino benzhydroxamic acid derivatives of formula (I) where R1, R2, R3, R4, R5, and R6 are hydrogen or substituent groups such as alkyl, and where R7 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. 翻译：公式（I）中的苯氨基苯甲酰羟肟酸衍生物，其中R1、R2、R3、R4、R5和R6是氢或取代基，例如烷基，而R7是氢或有机基团，是MEK的强效抑制剂，因此在治疗癌症和其他增生性疾病，如银屑病和再狭窄方面非常有效。
• Treatment of asthma with MEK inhibitors
  申请人：——

  公开号：US20040141924A1

  公开（公告）日：2004-07-22

  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: 1

  本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，特别是公式I和II的苯胺，来预防或治疗哮喘的方法。