4-(2-Fluoro-4-methylanilino)-7-methoxy-6-(1-propan-2-ylpiperidin-4-yl)cinnoline-3-carboxamide | 1041925-45-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(2-Fluoro-4-methylanilino)-7-methoxy-6-(1-propan-2-ylpiperidin-4-yl)cinnoline-3-carboxamide
• CAS: 1041925-45-4
• 化学式: C₂₅H₃₀FN₅O₂
• 分子量: 451.544
• InChiKey: GUYOKNBONQDXMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  93.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-(2-fluoro-4-methylphenylamino)-7-methoxy-6-(1,2,3,6-tetrahydropyridin-4-yl)cinnoline-3-carbonitrile 在 盐酸 、 sodium triacetoxyborohydride 、 10 wt% Pd(OH)2 on carbon 、 水 、 氢气 、 potassium hydroxide 作用下， 以 甲醇 、 水 、 溶剂黄146 、 1,2-二氯乙烷 、 叔丁醇 为溶剂， 55.0 ℃ 、1.0 MPa 条件下， 生成 4-(2-Fluoro-4-methylanilino)-7-methoxy-6-(1-propan-2-ylpiperidin-4-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

• STABILIZED ANGIOPOIETIN-2 ANTIBODIES AND USES THEREOF
  申请人：MedImmune Limited

  公开号：EP2247305A1

  公开（公告）日：2010-11-10
• [EN] STABILIZED ANGIOPOIETIN-2 ANTIBODIES AND USES THEREOF<br/>[FR] ANTICORPS STABILISÉS CONTRE L'ANGIOPOÏÉTINE-2 ET LEURS UTILISATIONS
  申请人：MEDIMMUNE LTD

  公开号：WO2009097325A1

  公开（公告）日：2009-08-06

  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.
• 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.