[4-Chloro-3-(4-methyl-pyridin-3-yl)-phenyl]-carbamic acid phenyl ester | 264617-24-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: [4-Chloro-3-(4-methyl-pyridin-3-yl)-phenyl]-carbamic acid phenyl ester
• CAS: 264617-24-5
• 化学式: C₁₉H₁₅ClN₂O₂
• 分子量: 338.793
• InChiKey: NDYZTHJFSQQVHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.32
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  51.22
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  5-甲氧基-6-(三氟甲基)吲哚啉 、 [4-Chloro-3-(4-methyl-pyridin-3-yl)-phenyl]-carbamic acid phenyl ester 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以49%的产率得到5-Methoxy-6-trifluoromethyl-2,3-dihydro-indole-1-carboxylic acid [4-chloro-3-(4-methyl-pyridin-3-yl)-phenyl]-amide
  参考文献：
  名称：

  Biarylcarbamoylindolines Are Novel and Selective 5-HT_2C Receptor Inverse Agonists:  Identification of 5-Methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]- 5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a Potential Antidepressant/Anxiolytic Agent

  摘要：

  The evolution, synthesis, and biological activity of a novel series of 5-HT2C receptor inverse agonists are reported. Biarylcarbamoylindolines have been identified with excellent 5-HT2C affinity and selectivity over 5-HT2A receptors. In addition, (pyridyloxypyridyl)carbamoylindolines have been discovered with additional selectivity over the closely related 5-HT2B receptor. Compounds from this series are inverse agonists at the human cloned 5-HT2C receptor, completely abolishing basal activity in a functional assay. The new series have reduced P450 inhibitory liability compared to a previously described series of 1-(3-pyridylcarbamoyl)indolines (Bromidge et al. J. Med. Chem. 1998, 41, 1598) from which they evolved. Compounds from this series showed excellent oral activity in a rat mCPP hypolocomotion model and in animal models of anxiety. On the basis of their favorable biological profile, 32 (SB-228357) and 40 (SB-243213) have been selected for further evaluation to determine their therapeutic potential for the treatment of CNS disorders such as depression and anxiety.

  DOI：

  10.1021/jm990388c
• 作为产物：
  描述：

  4-甲基吡啶-3-硼酸 在 盐酸 、 四(三苯基膦)钯 、 sodium carbonate 、 三乙胺 、 tin(ll) chloride 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 30.0h， 生成 [4-Chloro-3-(4-methyl-pyridin-3-yl)-phenyl]-carbamic acid phenyl ester
  参考文献：
  名称：

  Biarylcarbamoylindolines Are Novel and Selective 5-HT_2C Receptor Inverse Agonists:  Identification of 5-Methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]- 5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a Potential Antidepressant/Anxiolytic Agent

  摘要：

  The evolution, synthesis, and biological activity of a novel series of 5-HT2C receptor inverse agonists are reported. Biarylcarbamoylindolines have been identified with excellent 5-HT2C affinity and selectivity over 5-HT2A receptors. In addition, (pyridyloxypyridyl)carbamoylindolines have been discovered with additional selectivity over the closely related 5-HT2B receptor. Compounds from this series are inverse agonists at the human cloned 5-HT2C receptor, completely abolishing basal activity in a functional assay. The new series have reduced P450 inhibitory liability compared to a previously described series of 1-(3-pyridylcarbamoyl)indolines (Bromidge et al. J. Med. Chem. 1998, 41, 1598) from which they evolved. Compounds from this series showed excellent oral activity in a rat mCPP hypolocomotion model and in animal models of anxiety. On the basis of their favorable biological profile, 32 (SB-228357) and 40 (SB-243213) have been selected for further evaluation to determine their therapeutic potential for the treatment of CNS disorders such as depression and anxiety.

  DOI：

  10.1021/jm990388c