N-(2-(dimethylamino)ethyl)-4-hydroxyquinoline-2-carboxamide

• 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
• 英文名称: N-(2-(dimethylamino)ethyl)-4-hydroxyquinoline-2-carboxamide
• 英文别名: N-[2-(dimethylamino)ethyl]-4-oxo-1H-quinoline-2-carboxamide
• 化学式: C₁₄H₁₇N₃O₂
• 分子量: 259.308
• InChiKey: AODFDYHZUACIBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-(dimethylamino)ethyl)-4-hydroxyquinoline-2-carboxamide 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one hydrochloride
  参考文献：
  名称：

  犬尿酸乙酯的便捷一锅法合成及直接合成神经保护性犬尿酸及酰胺衍生物的探索

  摘要：

  犬尿酸 (KYNA) 是一种内源性分子，是离子型谷氨酸受体的非选择性拮抗剂，已被发现具有神经保护活性。KYNA 补充剂可能适用于治疗神经退行性疾病，但由于其极性性质，它不能穿过血脑屏障。因此，其不同的酯和酰胺衍生物被探索作为前药，可以穿过血脑屏障并原位转化为KYNA。然而，KYNA的许多酯和酰胺衍生物是使用不同的有机或金属催化剂通过偶联反应或多步合成合成的。在此，我们开发了一种新型的一锅法、无催化剂、方便地合成 KYNA 乙酯的方法，使用苯胺和乙炔二甲酸二乙酯在 DMF 中加热。我们还探索了以简单的方式合成 KYNA 和 KYNA 酰胺衍生物，分别通过水解和缩合获得了良好的收率。

  DOI：

  10.1021/acs.joc.3c00446
• 作为产物：
  描述：

  苯胺 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2-(dimethylamino)ethyl)-4-hydroxyquinoline-2-carboxamide
  参考文献：
  名称：

  犬尿酸乙酯的便捷一锅法合成及直接合成神经保护性犬尿酸及酰胺衍生物的探索

  摘要：

  犬尿酸 (KYNA) 是一种内源性分子，是离子型谷氨酸受体的非选择性拮抗剂，已被发现具有神经保护活性。KYNA 补充剂可能适用于治疗神经退行性疾病，但由于其极性性质，它不能穿过血脑屏障。因此，其不同的酯和酰胺衍生物被探索作为前药，可以穿过血脑屏障并原位转化为KYNA。然而，KYNA的许多酯和酰胺衍生物是使用不同的有机或金属催化剂通过偶联反应或多步合成合成的。在此，我们开发了一种新型的一锅法、无催化剂、方便地合成 KYNA 乙酯的方法，使用苯胺和乙炔二甲酸二乙酯在 DMF 中加热。我们还探索了以简单的方式合成 KYNA 和 KYNA 酰胺衍生物，分别通过水解和缩合获得了良好的收率。

  DOI：

  10.1021/acs.joc.3c00446

文献信息

• [EN] NOVEL TYPES OF C-3 SUBSTITUTED KINURENIC ACID DERIVATIVES WITH IMPROVED NEUROPROTECTIVE ACTIVITY<br/>[FR] NOUVEAUX TYPES DE DÉRIVÉS D'ACIDE KYNURÉNIQUE SUBSTITUÉS EN C-3 AYANT UNE ACTIVITÉ NEUROPROTECTRICE AMÉLIORÉE
  申请人：SZEGEDI TUDOMÁNYEGYETEM

  公开号：WO2017149333A1

  公开（公告）日：2017-09-08

  The invention relates to C-3 substituted kynurenic acid derivatives with the general formula (I) wherein R1 is C1-7alkyl-, R6R7N-C1-7alkyl-, C6-10aryl-C1-7alkyl group; R2 is H or C1-7alkyl group; or R1 and R2 with the nitrogen atom to which they are attached form a saturated or partially saturated 5-7 membered, optionally benzofused heterocyclic ring, optionally comprising additional N, O, S heteroatoms and optionally being substituted; R3 is -OH, C1-7alkyl-O-, -NH2, C1-7alkyl-NH-, C6-10aryl-C1-7alkyl-NH- or -NH- -(CH2)n-NR8R9 group wherein n is an integer from 1 to 3; R4 is H, C1-7alkyl-, C6-10aryl group or a halogen atom; R5 is H or C6-10aryl group; R6 is C1-7alkyl group; R7 is C1-7alkyl group; or R6 and R7 with the nitrogen atom to which they are attached form a saturated or partially saturated 5-7 membered, optionally benzofused heterocyclic ring, optionally comprising additional N, O, S heteroatoms and optionally being substituted; R8 is C1-7alkyl group; R9 is C1-7alkyl group; R8 and R9 with the nitrogen atom to which they are attached form a saturated or partially saturated 5-7 membered, optionally benzofused heterocyclic ring, optionally comprising additional N, O, S heteroatoms and optionally being substituted; and stereoisomers, tautomers and salts thereof. The invention relates to the pharmaceutical preparations comprising the compounds and stereoisomers, tautomers and pharmaceutically acceptable salts. The compounds of the invention have neuroprotective activity, may be used for the prevention and treatment of neurodegeneration, and for slowing down the development of the conditions and diseases associated with a decline in cognitive abilities.

  该发明涉及具有一般式(I)的C-3取代基的酮尿酸衍生物，其中R1为C1-7烷基，R6R7N-C1-7烷基，C6-10芳基-C1-7烷基基团；R2为H或C1-7烷基基团；或R1和R2与它们连接的氮原子形成饱和或部分饱和的5-7元环，可选地苯并杂环，可含有额外的N、O、S杂原子，可选地被取代；R3为-OH，C1-7烷氧基，-NH2，C1-7烷基-NH-，C6-10芳基-C1-7烷基-NH-或-NH-(CH2)n-NR8R9基团，其中n为1至3的整数；R4为H，C1-7烷基，C6-10芳基或卤原子；R5为H或C6-10芳基；R6为C1-7烷基；R7为C1-7烷基；或R6和R7与它们连接的氮原子形成饱和或部分饱和的5-7元环，可选地苯并杂环，可含有额外的N、O、S杂原子，可选地被取代；R8为C1-7烷基；R9为C1-7烷基；R8和R9与它们连接的氮原子形成饱和或部分饱和的5-7元环，可选地苯并杂环，可含有额外的N、O、S杂原子，可选地被取代；以及它们的立体异构体、互变异构体和盐。该发明涉及包含这些化合物及其立体异构体、互变异构体和药用可接受盐的药物制剂。该发明的化合物具有神经保护活性，可用于预防和治疗神经退行性疾病，并减缓与认知能力下降相关的症状和疾病的发展。
• Synthesis of New C-3 Substituted Kynurenic Acid Derivatives
  作者：Bálint Lőrinczi、Antal Csámpai、Ferenc Fülöp、István Szatmári

  DOI：10.3390/molecules25040937

  日期：——

  substituents attached to position 3 on the aminoalkylation was also investigated. Thus, reactions of 3-carbamoyl-substituted precursors with tertiary amine containing side-chains were also tested to afford new KYNA derivatives with two potential cationic centers. By means of NMR spectroscopic measurements, supported by DFT calculations, the dominant tautomer form of KYNA derivatives was also determined.

  犬尿烯酸 (KYNA) 作为富电子芳香体系在改良曼尼希反应中的应用已得到研究。通过使用存在于许多生物活性产物中的胺，如吗啉、哌啶或 N-甲基哌嗪和反应性明显不同的醛，如甲醛和苯甲醛，测试了反应的扩展可能性。还研究了连接到 3 位的取代基对氨基烷基化的影响。因此，还测试了 3-氨基甲酰基取代的前体与含有侧链的叔胺的反应，以提供具有两个潜在阳离子中心的新 KYNA 衍生物。通过由 DFT 计算支持的 NMR 光谱测量，还确定了 KYNA 衍生物的主要互变异构体形式。
• Types of C-3 substituted kynurenic acid derivatives with improved neuroprotective activity
  申请人：SZEGEDI TUDOMÁNYEGYETEM

  公开号：US10870633B2

  公开（公告）日：2020-12-22

  The invention relates to C-3 substituted kynurenic acid derivatives with the general formula (I) wherein R1 is C1-7alkyl-, R6R7N—C1-7alkyl-, C6-10aryl-C1-7alkyl group; R2 is H or C1-7alkyl group; or R1 and R2 with the nitrogen atom to which they are attached form a saturated or partially saturated 5-7 membered, optionally benzofused heterocyclic ring, optionally comprising additional N, O, S heteroatoms and optionally being substituted; R3 is —OH, C1-7alkyl-O—, —NH2, C1-7alkyl-NH—, C6-10aryl-C1-7alkyl-NH— or —NH— —(CH2)n—NR8R9 group wherein n is an integer from 1 to 3; R4 is H, C1-7alkyl-, C6-10aryl group or a halogen atom; R5 is H or C6-10aryl group; R6 is C1-7alkyl group; R7 is C1-7alkyl group; or R6 and R7 with the nitrogen atom to which they are attached form a saturated or partially saturated 5-7 membered, optionally benzofused heterocyclic ring, optionally comprising additional N, O, S heteroatoms and optionally being substituted; R8 is C1-7alkyl group; R9 is C1-7alkyl group; R8 and R9 with the nitrogen atom to which they are attached form a saturated or partially saturated 5-7 membered, optionally benzofused heterocyclic ring, optionally comprising additional N, O, S heteroatoms and optionally being substituted; and stereoisomers, tautomers and salts thereof. The invention relates to the pharmaceutical preparations comprising the compounds and stereoisomers, tautomers and pharmaceutically acceptable salts. The compounds of the invention have neuroprotective activity, may be used for the prevention and treatment of neurodegeneration, and for slowing down the development of the conditions and diseases associated with a decline in cognitive abilities.

  本发明涉及具有通式（I）的 C-3 取代的犬尿酸衍生物，其中 R1 是 C1-7 烷基、R6R7N-C1-7烷基、C6-10 芳基-C1-7烷基；R2 是 H 或 C1-7 烷基；或 R1 和 R2 与它们所连接的氮原子形成饱和或部分饱和的 5-7 位元、任选苯并杂环，任选包括额外的 N、O、S 杂原子并任选被取代；R3 是 -OH、C1-7 烷基-O-、-NH2、C1-7 烷基-NH-、C6-10 芳基-C1-7 烷基-NH- 或 -NH- -(CH2)n-NR8R9 基团，其中 n 是 1 到 3 的整数；R4 是 H、C1-7 烷基、C6-10 芳基或卤原子；R5 是 H 或 C6-10 芳基；R6 是 C1-7 烷基；R7 是 C1-7 烷基；或 R6 和 R7 与它们所连接的氮原子形成饱和或部分饱和的 5-7 位元、任选苯并杂环，任选包括额外的 N、O、S 杂原子并任选被取代；R8是C1-7烷基；R9是C1-7烷基；R8和R9与它们所连接的氮原子形成饱和或部分饱和的5-7个成员的、可选地包含额外的N、O、S杂原子并可选地被取代的杂环；以及它们的立体异构体、同系物和盐。本发明涉及包含本发明化合物及其立体异构体、同系物和药学上可接受的盐的药物制剂。本发明的化合物具有神经保护活性，可用于预防和治疗神经变性，以及减缓与认知能力下降相关的病症和疾病的发展。
• NOVEL TYPES OF C-3 SUBSTITUTED KINURENIC ACID DERIVATIVES WITH IMPROVED NEUROPROTECTIVE ACTIVITY
  申请人：Szegedi Tudományegyetem

  公开号：EP3423444A1

  公开（公告）日：2019-01-09
• NOVEL TYPES OF C-3 SUBSTITUTED KYNURENIC ACID DERIVATIVES WITH IMPROVED NEUROPROTECTIVE ACTIVITY
  申请人：SZEGEDI TUDOMÁNYEGYETEM

  公开号：US20190106409A1

  公开（公告）日：2019-04-11

  The invention relates to C-3 substituted kynurenic acid derivatives with the general formula (I) wherein R 1 is C 1-7 alkyl-, R 6 R 7 N-C 1-7 alkyl group; C 6-10 aryl-C 1-7 alkyl group; R 2 is H or C 1-7 alkyl group; or R 1 and R 2 with the nitrogen atom to which they are attached form a saturated or partially saturated 5-7 membered, optionally benzofused heterocyclic ring, optionally comprising additional N, O, S heteroatoms and optionally being substituted; R 3 is —OH, C 1-7 alkyl-O—, —NH 2 , C 1-7 alkyl-NH—, C 6-10 aryl-C 1-7 alkyl-NH— or —NH—(CH 2 ) n —NR 8 R 9 group wherein n is an integer from 1 to 3; R 4 is H, C 6-10 aryl group or a halogen atom; R 5 is H or C 6-10 aryl group; R6 is C 1-7 alkyl group; R 7 is C 1-7 alkyl group; or R 6 and R 7 with the nitrogen atom to which they are attached form a saturated or partially saturated 5-7 membered, optionally benzofused heterocyclic ring, optionally comprising additional N, O, S heteroatoms and optionally being substituted; R 8 is C 1-7 alkyl group; R 9 is C 1-7 alkyl group; R 8 and R 9 with the nitrogen atom to which they are attached form a saturated or partially saturated 5-7 membered, optionally benzofused heterocyclic ring, optionally comprising additional N, O, S heteroatoms and optionally being substituted; and stereoisomers, tautomers and salts thereof. The invention relates to the pharmaceutical preparations comprising the compounds and stereoisomers, tautomers and pharmaceutically acceptable salts. The compounds of the invention have neuroprotective activity, may be used for the prevention and treatment of neurodegeneration, and for slowing down the development of the conditions and diseases associated with a decline in cognitive abilities.