2-[4-(pyridin-4-yloxy)phenyl]acetic acid

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[4-(pyridin-4-yloxy)phenyl]acetic acid
• 英文别名: 2-(4-Pyridin-4-yloxyphenyl)acetic acid
• 化学式: C₁₃H₁₁NO₃
• 分子量: 229.235
• InChiKey: DIHMHEGBWXOEAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[4-(pyridin-4-yloxy)phenyl]acetic acid 、 5-叔丁基-2-对甲苯基-2H-吡唑-3-胺 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-2-[4-(pyridin-4-yloxy)phenyl]acetamide
  参考文献：
  名称：

  ANTI-MUCUS DRUGS AND USES THEREFOR

  摘要：

  揭示了一种识别、生成和合成抑制MAPK13活性的化合物的方法。在各种实施方式中，本教导的化合物、其盐和前药可以用于治疗涉及过多粘液产生的疾病和紊乱。

  公开号：

  US20150183777A1
• 作为产物：
  描述：

  2,4-二氯吡啶 在 palladium on activated charcoal 、 氢气 、 potassium carbonate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 2-[4-(pyridin-4-yloxy)phenyl]acetic acid
  参考文献：
  名称：

  Structure–Activity Relationship Studies of Mitogen Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 and BCR-ABL1 Inhibitors Targeting Chronic Myeloid Leukemic Cells

  摘要：

  Clinically used BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia do not eliminate leukemic stem cells (LSC). It has been shown that MNK1 and 2 inhibitors prevent phosphorylation of eIF4E and eliminate the self-renewal capacity of LSCs. Herein, we describe the identification of novel dual MNK1 and 2 and BCR-ABL1 inhibitors, starting from the known kinase inhibitor 2. Initial structure activity relationship studies resulted in compound 27 with loss of BCR-ABL1 inhibition. Further modification led to orally bioavailable dual MNK1 and 2 and BCR-ABL1 inhibitors 53 and 54, which are efficacious in a mouse xenograft model and also reduce the level of phosphorylated eukaryotic translation initiation factor 4E in the tumor tissues. Kinase selectivity of these compounds is also presented.

  DOI：

  10.1021/acs.jmedchem.5b01712

文献信息

• US9187470B2
  申请人：——

  公开号：US9187470B2

  公开（公告）日：2015-11-17
• ANTI-MUCUS DRUGS AND USES THEREFOR
  申请人：WASHINGTON UNIVERSITY

  公开号：US20150183777A1

  公开（公告）日：2015-07-02

  Disclosed are methods of identifying, generating and synthesizing compounds that inhibit MAPK13 activity. In various embodiments, compounds, salts thereof and prodrugs thereof of the present teachings can be useful for the treatment of diseases and disorders that involve excess mucus production.

  揭示了一种识别、生成和合成抑制MAPK13活性的化合物的方法。在各种实施方式中，本教导的化合物、其盐和前药可以用于治疗涉及过多粘液产生的疾病和紊乱。
• Structure–Activity Relationship Studies of Mitogen Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 and BCR-ABL1 Inhibitors Targeting Chronic Myeloid Leukemic Cells
  作者：Joseph Cherian、Kassoum Nacro、Zhi Ying Poh、Samantha Guo、Duraiswamy A. Jeyaraj、Yun Xuan Wong、Melvyn Ho、Hai Yan Yang、Joma Kanikadu Joy、Zekui Perlyn Kwek、Boping Liu、John Liang Kuan Wee、Esther HQ Ong、Meng Ling Choong、Anders Poulsen、May Ann Lee、Vishal Pendharkar、Li Jun Ding、Vithya Manoharan、Yun Shan Chew、Kanda Sangthongpitag、Sharon Lim、S. Tiong Ong、Jeffrey Hill、Thomas H. Keller

  DOI：10.1021/acs.jmedchem.5b01712

  日期：2016.4.14

  Clinically used BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia do not eliminate leukemic stem cells (LSC). It has been shown that MNK1 and 2 inhibitors prevent phosphorylation of eIF4E and eliminate the self-renewal capacity of LSCs. Herein, we describe the identification of novel dual MNK1 and 2 and BCR-ABL1 inhibitors, starting from the known kinase inhibitor 2. Initial structure activity relationship studies resulted in compound 27 with loss of BCR-ABL1 inhibition. Further modification led to orally bioavailable dual MNK1 and 2 and BCR-ABL1 inhibitors 53 and 54, which are efficacious in a mouse xenograft model and also reduce the level of phosphorylated eukaryotic translation initiation factor 4E in the tumor tissues. Kinase selectivity of these compounds is also presented.