4-[(2-fluoro-4-methylphenyl)amino]-7-methoxy-6-[4-(methylsulfonyl)piperazin-1-yl]cinnoline-3-carboxamide | 1194373-66-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-[(2-fluoro-4-methylphenyl)amino]-7-methoxy-6-[4-(methylsulfonyl)piperazin-1-yl]cinnoline-3-carboxamide
• 英文别名: 4-(2-Fluoro-4-methylanilino)-7-methoxy-6-(4-methylsulfonylpiperazin-1-yl)cinnoline-3-carboxamide
• CAS: 1194373-66-4
• 化学式: C₂₂H₂₅FN₆O₄S
• 分子量: 488.543
• InChiKey: ZXYGWQHDDCMWDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  139
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-[(2-fluoro-4-methylphenyl)amino]-7-methoxy-6-[4-(methylsulfonyl)piperazine-1-yl]cinnoline-3-carbonitrile 在 potassium hydroxide 作用下， 以 叔丁醇 为溶剂， 生成 4-[(2-fluoro-4-methylphenyl)amino]-7-methoxy-6-[4-(methylsulfonyl)piperazin-1-yl]cinnoline-3-carboxamide
  参考文献：
  名称：

  Mitigation of cardiovascular toxicity in a series of CSF-1R inhibitors, and the identification of AZD7507

  摘要：

  The potent and selective 3-amido-4-anilinoquinoline CSF-1R inhibitor AZ683 suffered from cardiovascular liabilities, which were linked to the off-target activities of the compound and ion channel activity in particular. Less basic and less lipophilic examples from both the quinoline and cinnoline series demonstrated cleaner secondary pharmacology profiles. Cinnoline 31 retained the required potency and oral PK profile, and was progressed through the safety screening cascade to be nominated into development as AZD7507. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.031

文献信息

• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2009136191A1

  公开（公告）日：2009-11-12

  The invention relates to chemical compounds of formula (I): or pharmaceutically acceptable salts thereof which possess CSF-IR kinase inhibitory activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm-blooded animal such as man.

  该发明涉及化学式(I)的化合物或其药用可接受盐，具有CSF-IR激酶抑制活性，因此在抗癌活性方面具有用途，可用于人体或动物体的治疗方法。该发明还涉及制备所述化学化合物的方法，含有它们的药物组合物，以及它们在制备用于在诸如人类之类的恒温动物体中产生抗癌效果的药物的用途。
• CHEMICAL COMPOUNDS
  申请人：Daly Kevin

  公开号：US20110190272A1

  公开（公告）日：2011-08-04

  The invention relates to chemical compounds of formula (I): or pharmaceutically acceptable salts thereof which possess CSF-IR kinase inhibitory activity and are accordingly useful for their anti-cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm-blooded animal such as man.

  本发明涉及化学式（I）的化合物或其药学上可接受的盐，具有CSF-IR激酶抑制活性，因此在抗癌活性方面有用，并因此适用于人体或动物体的治疗方法。本发明还涉及制造所述化学化合物的方法，含有它们的制药组合物以及它们在制造用于在温血动物（例如人）中产生抗癌效果的药物中的用途。
• Mitigation of cardiovascular toxicity in a series of CSF-1R inhibitors, and the identification of AZD7507
  作者：David A. Scott、Les A. Dakin、Kevin Daly、David J. Del Valle、R. Bruce Diebold、Lisa Drew、Jayachandran Ezhuthachan、Thomas W. Gero、Claude A. Ogoe、Charles A. Omer、Sean P. Redmond、Galina Repik、Kumar Thakur、Qing Ye、Xiaolan Zheng

  DOI：10.1016/j.bmcl.2013.06.031

  日期：2013.8

  The potent and selective 3-amido-4-anilinoquinoline CSF-1R inhibitor AZ683 suffered from cardiovascular liabilities, which were linked to the off-target activities of the compound and ion channel activity in particular. Less basic and less lipophilic examples from both the quinoline and cinnoline series demonstrated cleaner secondary pharmacology profiles. Cinnoline 31 retained the required potency and oral PK profile, and was progressed through the safety screening cascade to be nominated into development as AZD7507. (C) 2013 Elsevier Ltd. All rights reserved.