4-(piperazin-1-yl)quinolin-2(1H)-one | 91300-88-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(piperazin-1-yl)quinolin-2(1H)-one
• 英文别名: 4-piperazin-1-yl-1H-quinolin-2-one
• CAS: 91300-88-8
• 化学式: C₁₃H₁₅N₃O
• 分子量: 229.282
• InChiKey: SFBOVWRMAOHXGP-UHFFFAOYSA-N

物化性质

• 沸点：
  461.3±45.0 °C(Predicted)
• 密度：
  1.224±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-苯基-4-喹啉羧酸 、 4-(piperazin-1-yl)quinolin-2(1H)-one 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 以62%的产率得到4-(4-(2-phenylquinoline-4-carbonyl) piperazin-1-yl) quinolin-2(1H)-one
  参考文献：
  名称：

  基于喹啉甲酰胺核心部分的化合物抑制恶性疟原虫 falcipain-2：设计、合成和抗疟功效研究

  摘要：

  以 Falcipain-2 (FP2) 为靶点开发抗疟药是抗疟药发现和开发中一个很有前景的既定概念。FP2 是疟原虫恶性疟原虫的木瓜蛋白酶家族半胱氨酸蛋白酶的成员，在血红蛋白降解途径中具有重要作用。设计、合成了一系列新的喹啉甲酰胺类化合物并评估了其抗疟活性。我们将分子杂交策略与计算机药物设计相结合，以开发 FP2 抑制剂。发现Qs17、Qs18、Qs20和Qs21抑制 FP2 的体外结果在低微摩尔范围内，IC 50分别为 4.78、7.37、2.14 和 2.64 µM。在 25 种合成化合物中，四种化合物显示出显着的抗疟活性。这些化合物还比已建立的 FP2 抑制剂 E-64 更好地描述了形态学和食物液泡异常。总的来说，这些芳香族取代的喹啉甲酰胺可以作为开发新型抗疟药的有希望的先导。

  DOI：

  10.1016/j.bioorg.2020.104514
• 作为产物：
  描述：

  苯胺 在 盐酸 、 水 、 potassium carbonate 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 为溶剂， 反应 10.5h， 生成 4-(piperazin-1-yl)quinolin-2(1H)-one
  参考文献：
  名称：

  基于喹啉甲酰胺核心部分的化合物抑制恶性疟原虫 falcipain-2：设计、合成和抗疟功效研究

  摘要：

  以 Falcipain-2 (FP2) 为靶点开发抗疟药是抗疟药发现和开发中一个很有前景的既定概念。FP2 是疟原虫恶性疟原虫的木瓜蛋白酶家族半胱氨酸蛋白酶的成员，在血红蛋白降解途径中具有重要作用。设计、合成了一系列新的喹啉甲酰胺类化合物并评估了其抗疟活性。我们将分子杂交策略与计算机药物设计相结合，以开发 FP2 抑制剂。发现Qs17、Qs18、Qs20和Qs21抑制 FP2 的体外结果在低微摩尔范围内，IC 50分别为 4.78、7.37、2.14 和 2.64 µM。在 25 种合成化合物中，四种化合物显示出显着的抗疟活性。这些化合物还比已建立的 FP2 抑制剂 E-64 更好地描述了形态学和食物液泡异常。总的来说，这些芳香族取代的喹啉甲酰胺可以作为开发新型抗疟药的有希望的先导。

  DOI：

  10.1016/j.bioorg.2020.104514

文献信息

• TUMOR NECROSIS FACTOR ALPHA INHIBITORS AND THEIR USE IN THE TREATMENT OF HUMAN DISEASES
  申请人：Sircar Jagadish

  公开号：US20080139551A1

  公开（公告）日：2008-06-12

  treatment of a variety of disorders, including the treatment of pathological conditions associated with tumor necrosis factor alpha. The inhibitors of tumor necrosis factor alpha have the following structures: including stereoisomers, pharmaceutically acceptable salts, and solvates thereof, wherein substituents are as defined herein. Compositions containing an inhibitor of tumor necrosis factor alpha in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.

  治疗各种疾病，包括与肿瘤坏死因子α相关的病理条件的治疗。肿瘤坏死因子α的抑制剂具有以下结构：包括立体异构体、药用可接受的盐和溶剂，其中取代基如本文所定义。还提供了含有肿瘤坏死因子α抑制剂与药用可接受载体结合的组合物，以及使用方法。
• Inhibitors of macrophage migration inhibitory factor and methods for identifying the same
  申请人：Gaeta C.A. Federico

  公开号：US20070232613A1

  公开（公告）日：2007-10-04

  Inhibitors of MIF are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R 1 , R 2 , R 3 , R 4 , X, Y and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.

  提供了MIF抑制剂，可用于治疗多种疾病，包括与MIF活性相关的病理条件的治疗。MIF抑制剂具有以下结构：包括立体异构体，前药和其药物可接受的盐，其中n，R1，R2，R3，R4，X，Y和Z的定义如本文所述。还提供了含有MIF抑制剂与药物可接受载体结合的组合物，以及使用它们的方法。
• INHIBITORS OF MACROPHAGE MIGRATION INHIBITORY FACTOR AND METHODS FOR IDENTIFYING THE SAME
  申请人：Gaeta C.A. Federico

  公开号：US20070197547A1

  公开（公告）日：2007-08-23

  Inhibitors of MIF are provided which have utility in the treatment of a variety of disorders, including the treatment of pathological conditions associated with MIF activity. The inhibitors of MIF have the following structures: including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein n, R 1 , R 2 , R 3 , R 4 , X, Y and Z are as defined herein. Compositions containing an inhibitor of MIF in combination with a pharmaceutically acceptable carrier are also provided, as well as methods for use of the same.

  提供了MIF抑制剂，可用于治疗多种疾病，包括与MIF活性相关的病理性状况的治疗。MIF抑制剂具有以下结构：包括立体异构体、前药和其药学上可接受的盐，其中n、R1、R2、R3、R4、X、Y和Z的定义如本文所述。还提供了含有MIF抑制剂与药学上可接受的载体组合的组合物，以及使用它们的方法。
• Deciphering the robustness of pyrazolo-pyridine carboxylate core structure-based compounds for inhibiting α-synuclein in transgenic C. elegans model of Synucleinopathy
  作者：Mudasir Maqbool、Roshani Rajvansh、Kottapalli Srividya、Nasimul Hoda

  DOI：10.1016/j.bmc.2020.115640

  日期：2020.9

  Parkinson's disease (PD), a calamitous neurodegenerative disorder with no cure till date, is closely allied with the misfolding and aggregation of alpha-Synuclein (alpha-Syn). Inhibition of alpha-Syn aggregation is one of the optimistic approaches for the treatment for PD. Here, we carried out hypothesis-driven studies towards synthesising a series of pyrazolo-pyridine carboxylate containing compounds (7a-7m) targeted at reducing deleterious alpha-Syn aggregation. The target compounds were synthesized through multi-step organic synthesis reactions. From docking studies, compounds 7b, 7g and 7i displayed better interaction with the key residues of alpha-Syn with values: -6.8, -8.9 and -7.2 Kcal/mol, respectively. In vivo transgenic C. elegans model of Synucleinopathy was used to evaluate the ability of the designed and synthesized compounds to inhibit alpha-Syn aggregation. These lead compounds 7b, 7g and 7i displayed 1.7, 2.4 and 1.5-fold inhibition of alpha-Syn with respect to the control. Further, the strategy of employing pyrazolo-pyridine-based compounds worked with success and these scaffolds could be further modified and validated for betterment of endpoints associated with PD.
• TOMINAGA, MITIAKI;YANAGI, NAGAO;KOGAVA, XIDEHNORI;NAKAGAVA, KADZUYUKI
  作者：TOMINAGA, MITIAKI、YANAGI, NAGAO、KOGAVA, XIDEHNORI、NAKAGAVA, KADZUYUKI

  DOI：——

  日期：——