2-(4-chloro-phenyl)-7-methyl-8H-imidazo[1,2-a]pyrimidin-5-one | 108847-71-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并[1，2-a]嘧啶
• 英文名称: 2-(4-chloro-phenyl)-7-methyl-8H-imidazo[1,2-a]pyrimidin-5-one
• 英文别名: 2-(4-chlorophenyl)-7-methylimidazo[1,2-a]pyrimidin-5-ol；2-(4-chloro-phenyl)-7-methyl-8H-imidazo[1,2-a]pyrimidin-5-one；2-(p-Chlor-phenyl)-5-hydroxy-7-methyl-imidazo<1,2-a>pyrimidin
• CAS: 108847-71-8
• 化学式: C₁₃H₁₀ClN₃O
• 分子量: 259.695
• InChiKey: XRNYZKQFXVLTPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.06
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  50.42
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-(4-chloro-phenyl)-7-methyl-8H-imidazo[1,2-a]pyrimidin-5-one 在 三氯氧磷 作用下， 反应 2.0h， 以32%的产率得到5-chloro-2-(4-chlorophenyl)-7-methylimidazo[1,2-a]pyrimidine
  参考文献：
  名称：

  Identification of Potent In Vivo Autotaxin Inhibitors that Bind to Both Hydrophobic Pockets and Channels in the Catalytic Domain

  摘要：

  Autotaxin (ATX, also known as ENPP2) is a predominant lysophosphatidic acid (LPA)-producing enzyme in the body, and LPA regulates various physiological functions, such as angiogenesis and wound healing, as well as pathological functions, including proliferation, metastasis, and fibrosis, via specific LPA receptors. Therefore, the ATX-LPA axis is a promising therapeutic target for dozens of diseases, including cancers, pulmonary and liver fibroses, and neuropathic pain. Previous structural studies revealed that the catalytic domain of ATX has a hydrophobic pocket and a hydrophobic channel; these serve to recognize the substrate, lysophosphatidylcholine (LPC), and deliver generated LPA to LPA receptors on the plasma membrane. Most reported ATX inhibitors bind to either the hydrophobic pocket or the hydrophobic channel. Herein, we present a unique ATX inhibitor that binds mainly to the hydrophobic pocket and also partly to the hydrophobic channel, inhibiting ATX activity with high potency and selectivity in vitro and in vivo. Notably, our inhibitor can rescue the cardia bifida (two hearts) phenotype in ATX-overexpressing zebrafish embryos.

  DOI：

  10.1021/acs.jmedchem.9b01967
• 作为产物：
  描述：

  2'-溴-4-氯苯乙酮 、 2-氨基-4-羟基-6-甲基嘧啶 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以58%的产率得到2-(4-chloro-phenyl)-7-methyl-8H-imidazo[1,2-a]pyrimidin-5-one
  参考文献：
  名称：

  Identification of Potent In Vivo Autotaxin Inhibitors that Bind to Both Hydrophobic Pockets and Channels in the Catalytic Domain

  摘要：

  Autotaxin (ATX, also known as ENPP2) is a predominant lysophosphatidic acid (LPA)-producing enzyme in the body, and LPA regulates various physiological functions, such as angiogenesis and wound healing, as well as pathological functions, including proliferation, metastasis, and fibrosis, via specific LPA receptors. Therefore, the ATX-LPA axis is a promising therapeutic target for dozens of diseases, including cancers, pulmonary and liver fibroses, and neuropathic pain. Previous structural studies revealed that the catalytic domain of ATX has a hydrophobic pocket and a hydrophobic channel; these serve to recognize the substrate, lysophosphatidylcholine (LPC), and deliver generated LPA to LPA receptors on the plasma membrane. Most reported ATX inhibitors bind to either the hydrophobic pocket or the hydrophobic channel. Herein, we present a unique ATX inhibitor that binds mainly to the hydrophobic pocket and also partly to the hydrophobic channel, inhibiting ATX activity with high potency and selectivity in vitro and in vivo. Notably, our inhibitor can rescue the cardia bifida (two hearts) phenotype in ATX-overexpressing zebrafish embryos.

  DOI：

  10.1021/acs.jmedchem.9b01967

文献信息

• Identification of Potent <i>In Vivo</i> Autotaxin Inhibitors that Bind to Both Hydrophobic Pockets and Channels in the Catalytic Domain
  作者：Mitsuyasu Kawaguchi、Takayoshi Okabe、Shinichi Okudaira、Kotaro Hama、Kuniyuki Kano、Hiroshi Nishimasu、Hidehiko Nakagawa、Ryuichiro Ishitani、Hirotatsu Kojima、Osamu Nureki、Junken Aoki、Tetsuo Nagano

  DOI：10.1021/acs.jmedchem.9b01967

  日期：2020.3.26

  Autotaxin (ATX, also known as ENPP2) is a predominant lysophosphatidic acid (LPA)-producing enzyme in the body, and LPA regulates various physiological functions, such as angiogenesis and wound healing, as well as pathological functions, including proliferation, metastasis, and fibrosis, via specific LPA receptors. Therefore, the ATX-LPA axis is a promising therapeutic target for dozens of diseases, including cancers, pulmonary and liver fibroses, and neuropathic pain. Previous structural studies revealed that the catalytic domain of ATX has a hydrophobic pocket and a hydrophobic channel; these serve to recognize the substrate, lysophosphatidylcholine (LPC), and deliver generated LPA to LPA receptors on the plasma membrane. Most reported ATX inhibitors bind to either the hydrophobic pocket or the hydrophobic channel. Herein, we present a unique ATX inhibitor that binds mainly to the hydrophobic pocket and also partly to the hydrophobic channel, inhibiting ATX activity with high potency and selectivity in vitro and in vivo. Notably, our inhibitor can rescue the cardia bifida (two hearts) phenotype in ATX-overexpressing zebrafish embryos.