ethyl 2-[9-[1-(4-chlorophenyl)ethyl]-6-fluoro-8-methylsulfonyl-1,2,3,4-tetrahydrocarbazol-1-yl]acetate | 1261174-85-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 2-[9-[1-(4-chlorophenyl)ethyl]-6-fluoro-8-methylsulfonyl-1,2,3,4-tetrahydrocarbazol-1-yl]acetate
• CAS: 1261174-85-9
• 化学式: C₂₅H₂₇ClFNO₄S
• 分子量: 492.011
• InChiKey: CLYCVPYZVCXPOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  73.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-[9-[1-(4-chlorophenyl)ethyl]-6-fluoro-8-methylsulfonyl-1,2,3,4-tetrahydrocarbazol-1-yl]acetate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 以100%的产率得到2-(9-(1-(4-chlorophenyl)ethyl)-6-fluoro-8-(methylsulfonyl)-2,3,4,9-tetrahydro-1H-carbazol-1-yl)acetic acid
  参考文献：
  名称：

  Potent and highly selective DP1 antagonists with 2,3,4,9-tetrahydro-1H-carbazole as pharmacophore

  摘要：

  We discovered that the introduction of a methyl group to the benzylic position of the N-benzyl group in lead compound 1a has a dramatic effect on improving the binding selectivity of this ligand for the prostanoid receptors DP1 (receptor for prostaglandin D(2)) as compared to TP (receptor for thromboxane A(2)). Based on this discovery, we have synthesized a series of potent and highly selective DP1 antagonists. Among them, compound 1h was identified as a highly selective DP1 antagonist with excellent overall properties. It has a K(i) of 0.43 nM to DP1 in binding assay and an IC(50) of 2.5 nM in the DP1 functional assay. Its selectivity for DP1 over TP (the most potent receptor after DP1) exceeds 750-fold based on both binding and functional assays. These properties make 1h a very potent and highly selective DP1 receptor antagonist suitable for investigating the biological functions of DP1 in normal physiology and models of disease (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.018
• 作为产物：
  描述：

  ethyl 2-(8-bromo-9-(1-(4-chlorophenyl)ethyl)-6-fluoro-2,3,4,9-tetrahydro-1H-carbazol-1-yl)acetate 、 sodium methansulfinate 在 copper(l) iodide 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 8.0h， 以73%的产率得到ethyl 2-[9-[1-(4-chlorophenyl)ethyl]-6-fluoro-8-methylsulfonyl-1,2,3,4-tetrahydrocarbazol-1-yl]acetate
  参考文献：
  名称：

  Potent and highly selective DP1 antagonists with 2,3,4,9-tetrahydro-1H-carbazole as pharmacophore

  摘要：

  We discovered that the introduction of a methyl group to the benzylic position of the N-benzyl group in lead compound 1a has a dramatic effect on improving the binding selectivity of this ligand for the prostanoid receptors DP1 (receptor for prostaglandin D(2)) as compared to TP (receptor for thromboxane A(2)). Based on this discovery, we have synthesized a series of potent and highly selective DP1 antagonists. Among them, compound 1h was identified as a highly selective DP1 antagonist with excellent overall properties. It has a K(i) of 0.43 nM to DP1 in binding assay and an IC(50) of 2.5 nM in the DP1 functional assay. Its selectivity for DP1 over TP (the most potent receptor after DP1) exceeds 750-fold based on both binding and functional assays. These properties make 1h a very potent and highly selective DP1 receptor antagonist suitable for investigating the biological functions of DP1 in normal physiology and models of disease (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.018