(6aR,9R)-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-7,9-dicarboxylic acid 9-diethylamide 7-phenylamide

• 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,9R)-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-7,9-dicarboxylic acid 9-diethylamide 7-phenylamide
• 英文别名: (6aR,9R)-N9,N9-diethyl-N7-phenyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-7,9(4H)-dicarboxamide；(6aR,9R)-9-N,9-N-diethyl-7-N-phenyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-7,9-dicarboxamide
• 化学式: C₂₆H₂₈N₄O₂
• 分子量: 428.534
• InChiKey: QIPWTYSOANVUKJ-WZONZLPQSA-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

• 作为反应物：
  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
• 作为产物：
  描述：

  异氰酸苯酯 、 6-去甲麦角酸二乙基酰胺 以 丙酮 为溶剂， 反应 3.0h， 生成 (6aR,9R)-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-7,9-dicarboxylic acid 9-diethylamide 7-phenylamide
  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

• Treatment and prevention of cardiovascular disease
  申请人：Edifice Health, Inc.

  公开号：US11359011B2

  公开（公告）日：2022-06-14

  The methods and compositions described herein improve cardiovascular outcomes using measures related to systemic chronic inflammation (the inflammatory age—iAge, the cardiovascular age—cAge, and levels of certain markers) to stratify patients into low risk and high risk groups. The personalized immune proteome signature creates an individualized initial therapy to reduce cAge and to convert high risk patients into low risk patients. High risk patients can be converted to low risk patients by treating the patients to reduce their cAge, iAge and/or improve their CRS.

  本文所述的方法和组合物利用与全身慢性炎症有关的指标（炎症年龄-iAge、心血管年龄-cAge 和某些标志物的水平）将患者分为低风险组和高风险组，从而改善心血管预后。个性化的免疫蛋白质组特征可创建个性化的初始疗法，以降低年龄，并将高风险患者转化为低风险患者。通过治疗降低患者的 cAge、iAge 和/或改善其 CRS，可将高风险患者转化为低风险患者。
• 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.
• WO2006/128658
  申请人：——

  公开号：——

  公开（公告）日：——
• Treatment and Prevention of Cardiovascular Disease
  申请人：Edifice Health, Inc.

  公开号：US20210040195A1

  公开（公告）日：2021-02-11

  The methods and compositions described herein improve cardiovascular outcomes using measures related to systemic chronic inflammation (the inflammatory age—iAge, the cardiovascular age—cAge, and levels of certain markers) to stratify patients into low risk and high risk groups. The personalized immune proteome signature creates an individualized initial therapy to reduce cAge and to convert high risk patients into low risk patients. High risk patients can be converted to low risk patients by treating the patients to reduce their cAge, iAge and/or improve their CRS.
• Compounds and Methods for Modifying iAge
  申请人：Edifice Health, Inc,

  公开号：US20210315921A1

  公开（公告）日：2021-10-14

  The compounds and methods described herein can improve iAge (Inflammatory Age) of patients with a specific immunotype. For example, a patients iAge can be moved into a responders cohort from a non-responders cohort for an immunotherapy. The compounds and methods described herein can also improve cardiovascular patient outcomes using cAge to stratify CVD patients into risk cohorts for therapy and monitoring. Higher risk CVD patients can be converted to lower risk patients by treating the patients with molecules that reduce their cAge.