4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-2-carboxamide | 1254645-52-7

• 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: 4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-2-carboxamide
• 英文别名: 2-(2-N-pyrrolidylethyl-amino-1-carbonyl)-1H-quinolin-4-one；4-oxo-N-(2-pyrrolidin-1-ylethyl)-1H-quinoline-2-carboxamide
• CAS: 1254645-52-7
• 化学式: C₁₆H₁₉N₃O₂
• 分子量: 285.346
• InChiKey: GVRRBLARLZSSHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  聚合甲醛 、 哌啶 、 4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-2-carboxamide 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以82%的产率得到4-hydroxy-3-((piperidin-1-yl)methyl)-N-(2-(pyrrolidin-1-yl)ethyl)quinoline-2-carboxamide
  参考文献：
  名称：

  新型 C-3 取代犬尿酸衍生物的合成

  摘要：

  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。

  DOI：

  10.3390/molecules25040937

文献信息

• [EN] KYNURENIC ACID ANALOGUES, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND USE OF SAID COMPOUNDS FOR THE TREATMENT OF HEADACHE<br/>[FR] ANALOGUES DE L'ACIDE KYNURÉNIQUE, COMPOSITIONS PHARMACEUTIQUES CONTENANT CEUX-CI, ET UTILISATION DESDITS COMPOSÉS POUR LE TRAITEMENT DES CÉPHALÉES
  申请人：UNIV SZEGEDI

  公开号：WO2010128345A1

  公开（公告）日：2010-11-11

  The present invention is directed to novel kynurenic acid (KYNA) derivatives of the general formula (I) - and pharmaceutically acceptable salts, amides, all possible stereoisomers, including diastereoisomers and/or enantiomers, racemates and mixtures thereof, as well as a process for the preparation thereof, pharmaceutical compositions containing same, and use thereof for the manufacture of pharmaceutical compositions useful in the treatment of headaches, particularly non- neurodegenerative migraine.

  本发明涉及一种新型的酪氨酸酸（KYNA）衍生物，其通式为（I）-及其药学上可接受的盐、酰胺、所有可能的立体异构体，包括顺反异构体和/或对映异构体、外消旋体和混合物，以及其制备方法、含有其的药物组合物，以及用于制造用于治疗头痛，特别是非神经退行性偏头痛的药物组合物的用途。
• 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
• USE OF KYNURENIC ACID AMIDE DERIVATIVES FOR THE TREATMENT OF HUNTINGTON'S DISEASE
  申请人：Vécsei László

  公开号：US20130172346A1

  公开（公告）日：2013-07-04

  The invention is directed to kynurenic acid analogues and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing said compounds for treating the symptoms of Huntington's disease and preventing the development of the symptoms.
• 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.