(6aR,9S)-N9,N9-diethyl-N7-phenyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-7,9(4H)-dicarboxamide | 1198111-12-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 麦角林及其衍生物
• 英文名称: (6aR,9S)-N9,N9-diethyl-N7-phenyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-7,9(4H)-dicarboxamide
• 英文别名: (6aR,9S)-9-N,9-N-diethyl-7-N-phenyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-7,9-dicarboxamide
• CAS: 1198111-12-4
• 化学式: C₂₆H₂₈N₄O₂
• 分子量: 428.534
• InChiKey: QIPWTYSOANVUKJ-FDDCHVKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  68.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (6aR,9R)-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-7,9-dicarboxylic acid 9-diethylamide 7-phenylamide 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 (6aR,9S)-N9,N9-diethyl-N7-phenyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-7,9(4H)-dicarboxamide
  参考文献：
  名称：

  特殊麦角灵是趋化因子受体CXCR3的高选择性强效拮抗剂：一种有前途的铅的发现，表征和初步SAR

  摘要：

  特殊麦角灵1是趋化因子受体CXCR3的高效，选择性拮抗剂。该LSD相关化合物的惊人的选择性可以通过由分子的脲部分引起的麦角灵核心结构的不同电子和空间特性来解释。讨论了这种有前途的先导化合物的发现，生物制药性能和一阶衍生物。

  DOI：

  10.1016/j.bmcl.2009.09.002

文献信息

• Special ergolines efficiently inhibit the chemokine receptor CXCR3 in blood
  作者：Gebhard Thoma、Rolf Baenteli、Ian Lewis、Darryl Jones、Jiri Kovarik、Markus B. Streiff、Hans-Guenter Zerwes

  DOI：10.1016/j.bmcl.2011.06.070

  日期：2011.8

  The structure-activity relationship of highly potent special ergolines which selectively block the chemokine receptor CXCR3 is reported. The most potent compounds showed IC50 values below 10 nM in both ligand binding and Ca2+-mobilization assays. However, these compounds were poorly active in an assay that measures receptor occupancy in blood. Introduction of polar substituents led to derivatives with IC50 values below 10 nM in this assay. Among them was compound 11a which showed both a favorable PK profile and cross reactivity with rodent CXCR3 making it a promising tool compound to further explore the role of CXCR3 in animal models. (C) 2011 Elsevier Ltd. All rights reserved.
• Special ergolines are highly selective, potent antagonists of the chemokine receptor CXCR3: Discovery, characterization and preliminary SAR of a promising lead
  作者：Gebhard Thoma、Rolf Baenteli、Ian Lewis、Trixie Wagner、Lukas Oberer、Wolfgang Blum、Fraser Glickman、Markus B. Streiff、Hans-Guenter Zerwes

  DOI：10.1016/j.bmcl.2009.09.002

  日期：2009.11

  The special ergoline 1 is a highly potent, selective antagonist of the chemokine receptor CXCR3. The surprising selectivity of this LSD-related compound can be explained by different electronic and steric properties of the ergoline core structure caused by the urea portion of the molecule. Discovery, biopharmaceutical properties and first derivatives of this promising lead compound are discussed.

  特殊麦角灵1是趋化因子受体CXCR3的高效，选择性拮抗剂。该LSD相关化合物的惊人的选择性可以通过由分子的脲部分引起的麦角灵核心结构的不同电子和空间特性来解释。讨论了这种有前途的先导化合物的发现，生物制药性能和一阶衍生物。