5,6-dihydro-8-(1-hydroxy-2-methylpropyl)-2-methyl-1-<2-<4-(4-methyl-2-pyridinyl)-1-piperazinyl>ethyl>-4H-pyrrolo<3,2,1-ij>quinoline | 148490-10-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5,6-dihydro-8-(1-hydroxy-2-methylpropyl)-2-methyl-1-<2-<4-(4-methyl-2-pyridinyl)-1-piperazinyl>ethyl>-4H-pyrrolo<3,2,1-ij>quinoline
• 英文别名: 5,6-dihydro-8-(2-methyl-1-hydroxypropyl)-2-methyl-1-{2-[4-(4-methylpyridin-2-yl)piperazin-1-yl]-ethyl}-4H-pyrrolo[3,2,1-ij]quinoline；5,6-Dihydro-8-(1-hydroxy-2-methylpropyl)-2-methyl-1-{2-[4-(4-methylpyridin-2-yl)piperazin-1-yl]ethyl}-4H-pyrrolo-[3,2,1-ij]quinoline；2-Methyl-1-[2-methyl-3-[2-[4-(4-methylpyridin-2-yl)piperazin-1-yl]ethyl]-1-azatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraen-6-yl]propan-1-ol
• CAS: 148490-10-2
• 化学式: C₂₈H₃₈N₄O
• 分子量: 446.636
• InChiKey: DZJOJNOUNUUCOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  44.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,6-dihydro-8-(1-hydroxy-2-methylpropyl)-2-methyl-1-<2-<4-(4-methyl-2-pyridinyl)-1-piperazinyl>ethyl>-4H-pyrrolo<3,2,1-ij>quinoline 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 6.0h， 生成 5,6-dihydro-2-methyl-8-(2-methylpropenyl)-1-<2-<4-(4-methyl-2-pyridinyl)-1-piperazinyl>ethyl>-4H-pyrrolo<3,2,1-ij>quinoline
  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：

  5,6-dihydro-2-methyl-1-<2-<4-(4-methyl-2-pyridinyl)-1-piperazinyl>-2-oxoethyl>-8-(1-oxo-2-methylpropyl)-4H-pyrrolo<3,2,1-ij>quinoline 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以67%的产率得到5,6-dihydro-8-(1-hydroxy-2-methylpropyl)-2-methyl-1-<2-<4-(4-methyl-2-pyridinyl)-1-piperazinyl>ethyl>-4H-pyrrolo<3,2,1-ij>quinoline
  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

文献信息

• 7-fused 2-(piperazinoalkyl) indole derivatives, intermediates and
  申请人：Kali-Chemie Pharma GmbH

  公开号：US05324725A1

  公开（公告）日：1994-06-28

  Pharmacologically active compounds having anti-allergic properties corresponding to the formula I ##STR1## which can be mono- or disubstituted in the phenyl ring and their acid addition salts and/or S-mono- or dioxides of sulfur-containing compounds of the formula I are described, together with processes and intermediates for their preparation.

  具有抗过敏性能的药理活性化合物对应于公式I ##STR1##，该化合物可以在苯环中单取代或双取代，并描述了它们的酸盐和/或含有硫的化合物的S-单取代物或二氧化物，以及用于它们制备的过程和中间体。
• 1,7-anellierte 2-(Piperazino-alkyl)indol-Derivate sowie Verfahren und Zwischenprodukte zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
  申请人：Kali-Chemie Pharma GmbH

  公开号：EP0529452A2

  公开（公告）日：1993-03-03

  Es werden pharmakologisch wirksame Verbindungen der allgemeinen Formel welche im Phenylring mono- oder disubstituiert sein können und worin R3 Wasserstoff, niederes Alkyl, welches gegebenenfalls durch Hydroxy substituiert sein kann, niederes Alkenyl, C3-C6-Cycloalkyl, C4-C7-Cycloalkylalkyl oder eine gegebenenfalls im Phenylring substituierte Phenyl- oder Phenylniederalkylgruppe bedeutet, R4 Wasserstoff, Alkyl mit 1 - 7 Kohlenstoffatomen, welches gegebenenfalls durch Hydroxy substituiert sein kann, C3-C7-Alkenyl, C3-C6-Cycloalkyl, C4-C7-Cycloalkylalkyl oder eine gegebenenfalls im Phenylring substituierte Phenyl- oder Phenylniederalkylgruppe bedeutet, A eine gegebenenfalls durch niederes Alkyl substituierte Alkylenkette mit 1 - 2 Kohlenstoffatomen, eine Bindung, Sauerstoff oder Schwefel bedeutet, Z eine gegebenenfalls durch niederes Alkyl oder Hydroxy substituierte Alkylenkette mit 2 - 4 Kohlenstoffatomen bedeutet, B Stickstoff oder die CH-Gruppe bedeutet, R5 einen gegebenenfalls substituierten Pyridyl- oder Phenylrest bedeutet, und D eine Bindung darstellt oder, falls B die CH-Gruppe und R5 einen gegebenenfalls substituierten Phenylrest bedeuten, auch die CO-Gruppe darstellen kann, und deren Säureadditionssalze und/oder S-Mono- oder -Dioxide von schwefelhaltigen Verbindungen der Formel I beschrieben, sowie Verfahren und Zwischenprodukte zu ihrer Herstellung.

  具有药理活性的通式化合物 其苯基环可以是单取代或二取代的，其中 R3 是氢、可任选被羟基取代的低级烷基、低级烯基、C3-C6-环烷基、C4-C7-环烷基烷基或在苯基环上任选被取代的苯基或苯基-低级烷基、 R4 是氢、具有 1-7 个碳原子的烷基（可任选被羟基取代）、C3-C7-烯基、C3-C6-环烷基、C4-C7-环烷基烷基或在苯基环上任选被取代的苯基或苯基低级烷基、 A 表示具有 1-2 个碳原子的亚烷基链，可选择被低级烷基、键、氧或硫取代、 Z 表示具有 2 - 4 个碳原子的亚烷基链，可选择被低级烷基或羟基取代、 B 表示氮或 CH 基团、 R5 表示任选被取代的吡啶基或苯基，以及 D 代表键，或者，如果 B 代表 CH 基团，R5 代表任选取代的苯基，也可代表 CO 基团、 和它们的酸加成盐和/或式 I 含硫化合物的 S-单体或-二氧化物，以及制备它们的工艺和中间体。
• 1,7-anellierte 3-(Piperazino-alkyl)indol-Derivate sowie Verfahren und Zwischenprodukte zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
  申请人：Solvay Pharmaceuticals GmbH

  公开号：EP0529452B1

  公开（公告）日：1998-11-11
• US5324725A
  申请人：——

  公开号：US5324725A

  公开（公告）日：1994-06-28
• 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
  作者：Dominique Paris、Michel Cottin、Patrice Demonchaux、Guy Augert、Pierre Dupassieux、Patrick Lenoir、Michael J. Peck、Daniel Jasserand

  DOI：10.1021/jm00004a013

  日期：1995.2

  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.