PD 184161 | 212631-67-9

• 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: PD 184161
• 英文别名: 2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluoro-5-bromobenzamide；5-bromo-2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide
• CAS: 212631-67-9
• 化学式: C₁₇H₁₃BrClF₂IN₂O₂
• 分子量: 557.561
• InChiKey: VJNZMSLGVUSPCF-UHFFFAOYSA-N

物化性质

• 熔点：
  174-175 °C
• 密度：
  1.922±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• WGK Germany：
  3
• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为产物：
  描述：

  5-Bromo-2-(2-chloro-4-iodo-phenylamino)-3,4-difluoro-benzoic acid 、 O-环丙基甲基羟胺盐酸盐 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56%的产率得到PD 184161
  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

• COMBINATIONS OF MEK INHIBITORS AND RAF KINASE INHIBITORS AND USES THEREOF
  申请人：MINER Jeffrey

  公开号：US20120136030A1

  公开（公告）日：2012-05-31

  This invention concerns combinations of inhibitors of MEK, Raf protein kinases, and other kinases including VEGFR1-3 and PDGFR-β. This invention also concerns pharmaceutical compositions comprising the compounds described herein and methods of use of the compounds and compositions described herein, including the use in the treatment and/or prevention of cancer and other hyperproliferative disorders.

  这项发明涉及MEK、Raf蛋白激酶以及其他激酶（包括VEGFR1-3和PDGFR-β）的抑制剂的组合。这项发明还涉及包括本文所描述的化合物的药物组合物，以及所述化合物和组合物的使用方法，包括用于治疗和/或预防癌症和其他过度增殖性疾病的用途。
• 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。
• COMPOSITIONS AND METHODS FOR TREATMENT OF VIRAL DISEASES
  申请人：Johansen Lisa M.

  公开号：US20100009970A1

  公开（公告）日：2010-01-14

  The present invention features compositions, methods, and kits useful in the treatment of viral diseases. In certain embodiments, the viral disease is caused by a single stranded RNA virus, a flaviviridae virus, or a hepatic virus. In particular embodiments, the viral disease is viral hepatitis (e.g., hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E) and the agent or combination of agents includes sertraline, a sertraline analog, UK-416244, or a UK-416244 analog. Also featured are screening methods for identification of novel compounds that may be used to treat a viral disease.

  本发明涉及用于治疗病毒性疾病的组合物、方法和试剂盒。在某些实施方式中，病毒性疾病是由单链RNA病毒、黄病毒科病毒或肝病毒引起的。在特定实施方式中，病毒性疾病是病毒性肝炎（例如甲型肝炎、乙型肝炎、丙型肝炎、丁型肝炎、戊型肝炎），药剂或药剂组合包括舍曲林、舍曲林类似物、UK-416244或UK-416244类似物。还包括用于鉴定可用于治疗病毒性疾病的新化合物的筛选方法。
• [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。