3-({3-氨基甲酰基-4-[(3-甲氧基苯基)氨基]-8-甲基-6-喹啉基}磺酰基)苯甲酸 | 801311-41-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 3-({3-氨基甲酰基-4-[(3-甲氧基苯基)氨基]-8-甲基-6-喹啉基}磺酰基)苯甲酸
• 中文别名: 3-((3-氨基甲酰基-4-((3-甲氧基苯基)氨基)-8-甲基喹啉-6-基)磺酰基)苯甲酸
• 英文名称: 3-(3-carbamoyl-4-(3-methoxyphenylamino)-8-methylquinolin-6-ylsulfonyl)benzoic acid
• 英文别名: 3-[3-carbamoyl-4-(3-methoxyanilino)-8-methylquinolin-6-yl]sulfonylbenzoic acid
• CAS: 801311-41-1
• 化学式: C₂₅H₂₁N₃O₆S
• 分子量: 491.524
• InChiKey: SZZXZRJNNBZBOV-UHFFFAOYSA-N

物化性质

• 沸点：
  792.1±60.0 °C(Predicted)
• 密度：
  1.434±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  157
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-({3-氨基甲酰基-4-[(3-甲氧基苯基)氨基]-8-甲基-6-喹啉基}磺酰基)苯甲酸 在 四丁基氟化铵 、 三乙酰氧基硼氢化钠 、 戴斯-马丁氧化剂 、 溶剂黄146 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 (R)-6-[[3-[[8-[[2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino]octyl]carbamoyl]phenyl]sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methylquinoline-3-carboxamide
  参考文献：
  名称：

  BI-FUNCTIONAL QUINOLINE ANALOGS

  摘要：

  提供的是以下化合物的结构式：其中X是：R1和R2，与它们结合的苯基一起可以形成一个螺环的、融合的杂环环，所有其他变量如本文所定义，以及它们在治疗肺部炎症或支气管痉挛中的应用，以及包含它们的组合物和制备这些化合物的方法。

  公开号：

  US20110275622A1
• 作为产物：
  描述：

  6-iodo-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide 在 Oxone 、 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 双(2-二苯基磷苯基)醚 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 3-({3-氨基甲酰基-4-[(3-甲氧基苯基)氨基]-8-甲基-6-喹啉基}磺酰基)苯甲酸
  参考文献：
  名称：

  Repurposing Human PDE4 Inhibitors for Neglected Tropical Diseases. Evaluation of Analogs of the Human PDE4 Inhibitor GSK-256066 as Inhibitors of PDEB1 ofTrypanosoma brucei

  摘要：

  Cyclic nucleotide phosphodiesterases (PDEs) have been identified as important enzyme targets for drug development in both humans and Trypanosoma brucei, the causative agent of human African trypanosomiasis. With this in mind, we recently reported the profiling of a range of human phosphodiesterase inhibitors, showing that human PDE4 inhibitors tend to display the best potency against the trypanosomal phosphodiesterase TbrPDEB1. Among these was GSK‐256066, a potent inhibitor of human PDE4 and a weak inhibitor of TbrPDEB1. In this report, we describe the results of a structure–activity relationship study of this chemotype, leading to the discovery of analogs with improved potency against TbrPDEB1 and micromolar inhibition of T. brucei cellular growth. We rationalize the potency trends via molecular docking of the new inhibitors into a recently reported apo structure of TbrPDEB1. The studies in this article will inform future efforts in repurposing human PDE inhibitors as antitrypanosomal agents.

  DOI：

  10.1111/cbdd.12443

文献信息

• [EN] QUINOLINE DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS<br/>[FR] DERIVES DE QUINOLEINE UTILISES EN TANT QU'INHIBITEURS DE LA PHOSPHODIESTERASE
  申请人：GLAXO GROUP LTD

  公开号：WO2004103998A1

  公开（公告）日：2004-12-02

  There are provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R19, R20 and R34 are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

  根据本发明提供了化合物的新结构，其化学式为（I）或其药用盐，其中R1、R2、R19、R20和R34如规范中所述，以及制备这些化合物的方法、含有它们的配方和它们在治疗炎症性疾病中的用途。
• Quinoline derivatives as phosphodiesterase inhibitors
  申请人：Barker David Michael

  公开号：US20060178416A1

  公开（公告）日：2006-08-10

  There are provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R19, R20, and R34 are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

  根据本发明提供了公式(I)的新化合物或其药学上可接受的盐，其中R1、R2、R19、R20和R34如规范所述，以及制备它们的过程、包含它们的制剂和它们在治疗炎症性疾病方面的用途。
• Quinoline Derivatives As Phosphodiesterase Inhibitors
  申请人：Baldwin Ian Robert

  公开号：US20090312325A1

  公开（公告）日：2009-12-17

  There are provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R19, R20, and R34 are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

  根据本发明提供了一种新的化合物式(I)或其药学上可接受的盐，其中R1、R2、R19、R20和R34如规范所述，以及制备它们的过程、含有它们的制剂以及它们在治疗炎症性疾病方面的用途。
• Bi-functional quinoline analogs
  申请人：Baker William R.

  公开号：US08394829B2

  公开（公告）日：2013-03-12

  Provided are compounds of Formula I: wherein X is: R1 and R2 together with the phenyl to which they are bound may form a bicyclic, fused heterocyclic ring, and all other variables are as defined herein, as well as their use in treating pulmonary inflammation or bronchoconstriction and compositions comprising and processes for preparing the same.

  提供的是I式化合物：其中X为：R1和R2与它们所结合的苯基可能形成一个双环的、融合的杂环环，所有其他变量的定义如本文所述，以及它们在治疗肺部炎症或支气管收缩以及包含它们的组合物和制备这些化合物的过程中的使用。
• Quinoline derivatives as phosphodiesterase inhibitors
  申请人：GLAXO GROUP LIMITED

  公开号：EP1944305A1

  公开（公告）日：2008-07-16

  There are provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R19, R20 and R34 are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

  根据本发明提供了式 (I) 的新型化合物或其药学上可接受的盐类（其中 R1、R2、R19、R20 和 R34 如说明书所述）、制备它们的工艺、含有它们的制剂以及它们在治疗炎症性疾病中的用途。