<8-(cyclohexylmethyl)-5,6-dihydro-2-methyl-4H-pyrrolo<3,2,1-ij>quinolin-1-yl>acetic acid

• 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: <8-(cyclohexylmethyl)-5,6-dihydro-2-methyl-4H-pyrrolo<3,2,1-ij>quinolin-1-yl>acetic acid
• 英文别名: 2-[6-(Cyclohexylmethyl)-2-methyl-1-azatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraen-3-yl]acetic acid
• 化学式: C₂₁H₂₇NO₂
• 分子量: 325.451
• InChiKey: UMGXLNJESRGKAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-甲基-2-吡啶)哌嗪 、 <8-(cyclohexylmethyl)-5,6-dihydro-2-methyl-4H-pyrrolo<3,2,1-ij>quinolin-1-yl>acetic acid 在 N,N'-羰基二咪唑 作用下， 生成 2-(8-Cyclohexylmethyl-2-methyl-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-1-[4-(4-methyl-pyridin-2-yl)-piperazin-1-yl]-ethanone
  参考文献：
  名称：

  Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of Pyrrolo[3,2,1-ij]quinoline Derivatives: Potent Histamine and Platelet Activating Factor Antagonism and 5-Lipoxygenase Inhibitory Properties. Potential Therapeutic Application in Asthma

  摘要：

  A series of pyrrolo[3,2,1-ij]quinoline derivatives was synthesized and evaluated for their in vitro and in vivo activities against histamine, platelet activating factor (PAF), and leukotrienes which are recognized to be of importance in asthma. The structure-activity relationship studies have shown that the optimum moiety on the 1-position of the pyrroloquinoline nucleus is a 2-[4-(4-methyl-2-pyridinyl)-1-piperazinyl]ethyl chain in conjunction with a methyl group on the 2-position for potent antagonism of both histamine and PAF. The introduction of substituents on the 8- and 4-positions was also investigated in order to increase the potency of 5-lipoxygenase inhibition while retaining or improving the activities against histamine and PAF. This series is exemplified by 4-n-butyl-5,6-dihydro-8-hydroxy-2-methyl-1-[2-[4-(4-methyl- 2-pyridinyl)-1-piperazinyl]ethyl]-4H-pyrrolo[3,2,1-ij]quinoline (24, KC 11404) which was found to be active against all three of the selected mediators. Compound 24 was found to be orally active in guinea pig models against the histaminic phase of antigen-induced bronchospasm and PAF-induced bronchoconstriction (ED(50) = 1.9 and 2.1 mu mol/kg, respectively). When tested against the leukotriene-dependent phase of the antigen-induced bronchoconstriction, compound 24 showed the same potency as zileuton.

  DOI：

  10.1021/jm00004a013
• 作为产物：
  描述：

  ethyl <8-(cyclohexylcarbonyl)-5,6-dihydro-2-methyl-4H-pyrrolo<3,2,1-ij>quinolin-1-yl>acetate 在 氢氧化钾 、 一水合肼 作用下， 生成 <8-(cyclohexylmethyl)-5,6-dihydro-2-methyl-4H-pyrrolo<3,2,1-ij>quinolin-1-yl>acetic acid
  参考文献：
  名称：

  Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of Pyrrolo[3,2,1-ij]quinoline Derivatives: Potent Histamine and Platelet Activating Factor Antagonism and 5-Lipoxygenase Inhibitory Properties. Potential Therapeutic Application in Asthma

  摘要：

  A series of pyrrolo[3,2,1-ij]quinoline derivatives was synthesized and evaluated for their in vitro and in vivo activities against histamine, platelet activating factor (PAF), and leukotrienes which are recognized to be of importance in asthma. The structure-activity relationship studies have shown that the optimum moiety on the 1-position of the pyrroloquinoline nucleus is a 2-[4-(4-methyl-2-pyridinyl)-1-piperazinyl]ethyl chain in conjunction with a methyl group on the 2-position for potent antagonism of both histamine and PAF. The introduction of substituents on the 8- and 4-positions was also investigated in order to increase the potency of 5-lipoxygenase inhibition while retaining or improving the activities against histamine and PAF. This series is exemplified by 4-n-butyl-5,6-dihydro-8-hydroxy-2-methyl-1-[2-[4-(4-methyl- 2-pyridinyl)-1-piperazinyl]ethyl]-4H-pyrrolo[3,2,1-ij]quinoline (24, KC 11404) which was found to be active against all three of the selected mediators. Compound 24 was found to be orally active in guinea pig models against the histaminic phase of antigen-induced bronchospasm and PAF-induced bronchoconstriction (ED(50) = 1.9 and 2.1 mu mol/kg, respectively). When tested against the leukotriene-dependent phase of the antigen-induced bronchoconstriction, compound 24 showed the same potency as zileuton.

  DOI：

  10.1021/jm00004a013