4-[(2-fluoro-4-methylphenyl)amino]-6-{4-[(2R)-2-hydroxypropanoyl]piperazin-1-yl}-7-methoxycinnoline-3-carboxamide | 1041852-97-4

• 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]-6-{4-[(2R)-2-hydroxypropanoyl]piperazin-1-yl}-7-methoxycinnoline-3-carboxamide
• 英文别名: 4-(2-fluoro-4-methylphenylamino)-6-(4-((2R)-2-hydroxypropanoyl)piperazin-1-yl)-7-methoxycinnoline-3-carboxamide；4-(2-fluoro-4-methylanilino)-6-[4-[(2R)-2-hydroxypropanoyl]piperazin-1-yl]-7-methoxycinnoline-3-carboxamide
• CAS: 1041852-97-4
• 化学式: C₂₄H₂₇FN₆O₄
• 分子量: 482.515
• InChiKey: ZPBNIQBBVBKMAX-CQSZACIVSA-N

物化性质

• 沸点：
  735.2±70.0 °C(predicted)
• 密度：
  1.385±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  134
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  6-bromo-4-(2-fluoro-4-methylphenylamino)-7-methoxycinnoline-3-carbonitrile 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 palladium diacetate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 N,N-二异丙基乙胺 、 potassium hydroxide 、 sodium t-butanolate 作用下， 以 甲醇 、 N,N-二甲基乙酰胺 、 水 、 叔丁醇 为溶剂， 生成 4-[(2-fluoro-4-methylphenyl)amino]-6-{4-[(2R)-2-hydroxypropanoyl]piperazin-1-yl}-7-methoxycinnoline-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。
• 3-CINNOLINECARBOXAMIDE DERIVATIVES AND THEIR USE FOR TREATING CANCER
  申请人：Dakin Leslie

  公开号：US20090012084A1

  公开（公告）日：2009-01-08

  The invention relates to chemical compounds of formula (I): or pharmaceutically acceptable salts thereof which possess CSF-1R 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，其具有CSF-1R激酶抑制活性，因此在抗癌活性及人或动物体的治疗方法中有用。本发明还涉及制造所述化学化合物的过程，包含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的过程中的使用。
• 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。
• 3-cinnolinecarboxamide derivatives and their use for treating cancer
  申请人：AstraZeneca AB

  公开号：US07723337B2

  公开（公告）日：2010-05-25

  The invention relates to chemical compounds of formula (I): or pharmaceutically acceptable salts thereof which possess CSF-1R 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，其具有CSF-1R激酶抑制活性，因此在抗癌活性方面有用，并因此在人类或动物体的治疗方法中使用。本发明还涉及制造所述化学化合物的方法，包含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的使用。
• Stabilized angiopoietin-2 antibodies and uses thereof
  申请人：MedImmune Limited

  公开号：US10329345B2

  公开（公告）日：2019-06-25

  Stabilized antibodies directed to Angiopoeitin-2 and uses of such antibodies are described. Nucleic acid and amino acid sequences, hybridomas or other cell lines for expressing such antibodies are also provided.

  描述了针对 Angiopoeitin-2 的稳定抗体及其用途。还提供了表达这种抗体的核酸和氨基酸序列、杂交瘤或其他细胞系。