3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-N-methoxy-benzamide | 212630-53-0

• 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-difluoro-2-(4-iodo-2-methyl-phenylamino)-N-methoxy-benzamide
• 英文别名: 3,4-difluoro-2-(4-iodo-2-methylanilino)-N-methoxybenzamide
• CAS: 212630-53-0
• 化学式: C₁₅H₁₃F₂IN₂O₂
• 分子量: 418.182
• InChiKey: YKZJWZFIUUQRCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 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：
  5

反应信息

• 作为产物：
  描述：

  3-氯苯甲酰乙腈 、 PD 0169842 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73%的产率得到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

文献信息

• 4-BROMO OR 4-IODO PHENYLAMINO BENZHYDROXAMIC ACID DERIVATIVES AND THEIR USE AS MEK INHIBITORS
  申请人：Warner-Lambert Company LLC

  公开号：EP0993439B1

  公开（公告）日：2004-09-29
• TREATMENT OF ASTHMA WITH MEK INHIBITORS
  申请人：Warner-Lambert Company LLC

  公开号：EP1140062B1

  公开（公告）日：2005-04-06
• COMBINATION CHEMOTHERAPY COMPRISING A MITOTIC INHIBITOR AND A MEK INHIBITOR
  申请人：Warner-Lambert Company LLC

  公开号：EP1140291B1

  公开（公告）日：2005-11-23
• METHOD FOR TREATING CHRONIC PAIN USING MEK INHIBITORS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1202726A2

  公开（公告）日：2002-05-08
• [EN] METHOD FOR TREATING CHRONIC PAIN USING MEK INHIBITORS<br/>[FR] TRAITEMENT DES DOULEURS CHRONIQUES PAR DES INHIBITEURS DE MEK
  申请人：WARNER LAMBERT CO

  公开号：WO2001005392A2

  公开（公告）日：2001-01-25

  The invention features a method for treating chronic pain using a compound of formula (I) and 1 (A) which are shown in claim 1 and 26 of the application.