1-[4-[2-羟基-3-(5-喹啉基氧基)丙基]-1-哌嗪基]-2,2-二苯基乙酮 | 129716-58-1

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-[4-[2-羟基-3-(5-喹啉基氧基)丙基]-1-哌嗪基]-2,2-二苯基乙酮
• 英文名称: 5-[3-(4-(2,2-diphenylacetyl)piperazine-1-yl)-2-hydroxypropoxy]quinoline
• 英文别名: Dofequidar；MS-209；rac-1-{4-[2-hydroxy-3-(5-quinolinyloxy)propyl]piperazin-1-yl}-2,2-diphenylethan-1-one；5-[3-{4-(2,2diphenylacetyl)piperazin-1-yl}-2-hydroxypropoxy]quinoline；1-[4-(2-hydroxy-3-quinolin-5-yloxypropyl)piperazin-1-yl]-2,2-diphenylethanone
• CAS: 129716-58-1
• 化学式: C₃₀H₃₁N₃O₃
• 分子量: 481.594
• InChiKey: KLWUUPVJTLHYIM-UHFFFAOYSA-N

物化性质

• 沸点：
  720.8±60.0 °C(Predicted)
• 密度：
  1.228
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  65.9
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性方面，Dofequidar (MS-209) 是一种新型的喹啉类化合物，能够逆转由 P-糖蛋白 (P-gp) 介导的多药耐药性。

反应信息

• 作为反应物：
  描述：

  富马酸 、 1-[4-[2-羟基-3-(5-喹啉基氧基)丙基]-1-哌嗪基]-2,2-二苯基乙酮 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 3.0h， 生成 5-[3-{4-(2,2-diphenylacetyl)piperazin-1-yl}-2-hydroxypropoxy]quinoline fumarate
  参考文献：
  名称：

  [DE] VERFAHREN ZUR HERSTELLUNG VON REINSTEM RAC-1-{4-[2-HYDROXY-3-(5-QUINOLYLOXY)PROPYL] PIPERAZIN-1-YL}-2,2-DIPHENYLETHAN-1-ONE FUMARAT UND REINSTES RAC-1-{4-[2-HYDROXY-3-(5-QUINOLYLOXY)PROPYL]PIPERAZIN-1-YL}-2,2-DIPHENYLETHAN-1-ONE
  [EN] METHOD FOR PRODUCING THE PUREST RAC-1-{4-[2-HYDROXY-3-(5-QUINOLYLOXY)PROPYL] PIPERAZIN-1-YL}-2,2-DIPHENYLETHAN-1-ONE FUMARATE AND THE PUREST RAC-1-{4-[2-HYDROXY-3-(5-QUINOLYLOXY)PROPYL]PIPERAZIN-1-YL}-2,2-DIPHENYLETHAN-1-ONE FUMARATE
  [FR] PROCEDE DE PRODUCTION DE FUMARATE ULTRAPUR DE RAC-1-{4-[2-HYDROXY-3-(5-QUINOLYLOXY)PROPYL]-PIPERAZINE-1-YLE}2,2-DIPHENYLETHANE-1-ONE ET FUMARATE ULTRAPUR DE RAC-1-{4-[2-HYDROXY-3-(5-QUINOLYLOXY)PROPYL]-PIPERAZINE-1-YLE}2,2-DIPHENYLETHANE-1-ONE

  摘要：

  这项技术描述了一种制备最纯的富马酸盐rac-1-{4-[2-羟基-3-(5-喹诺氧基)丙基]-哌嗪-1-基}-2,2-二苯乙酮以及富马酸盐rac-1-{4-[2-羟基-3-(5-喹诺氧基)丙基]哌嗪-1-基}-2,2-二苯乙酮，其纯度至少为98.55%。

  公开号：

  WO2004099151A1
• 作为产物：
  描述：

  1-Diphenylacetyl-4-formylpiperazine 在 盐酸 作用下， 以 甲醇 、 异丙醇 为溶剂， 反应 4.0h， 生成 1-[4-[2-羟基-3-(5-喹啉基氧基)丙基]-1-哌嗪基]-2,2-二苯基乙酮
  参考文献：
  名称：

  新合成的喹啉衍生物的结构-活性关系用于逆转癌症中的多药耐药性。

  摘要：

  在体外检查了24种新合成的喹啉衍生物对肿瘤细胞多药耐药性（MDR）的影响。在低浓度下，这些化合物增强了[3H]长春新碱在K562 / ADM细胞中的积累，并逆转了肿瘤细胞MDR。结构-活性关系分析的结果表明，在高活性化合物中，疏水部分的两个芳基环偏离同一平面，因此它们能够与P-170糖蛋白（P-gp）的氢键供体相互作用pi-氢-pi相互作用。影响这些化合物的MDR-逆转活性的其他主要结构特征是哌嗪中的喹啉氮原子和碱性氮原子。此外，在高活性化合物中

  DOI：

  10.1021/jm960869l

文献信息

• Quinoline derivatives
  申请人：Mitsui Toatsu Chemicals, Incorporated

  公开号：US05112817A1

  公开（公告）日：1992-05-12

  Novel heterocyclic compounds, which are represented by the following general formula, useful as anticancer drug potentiaters having a potentiating effect on the incorporation of anticancer drugs into cancer cells, the compounds each synthesized by, for example, reacting a epoxy compound obtained by reacting a heterocyclic compound with an epihalogenohydrin, with an amine derivative.

  新颖的杂环化合物，以以下通用公式表示，作为抗癌药物增效剂，对抗癌药物的纳入癌细胞具有增效作用，这些化合物通过例如将由异环化合物与环氧卤水合物反应得到的环氧化合物与胺衍生物反应合成。
• Quinoline derivative fumarates
  申请人：Mitsui Toatsu Chemicals, Incorporated

  公开号：US05434155A1

  公开（公告）日：1995-07-18

  Compounds having an activity to stimulate the carcinostatic effect of carcinostatic agents, which can be expressed by the following general formula (1): ##STR1## in which A is ##STR2## (in which R.sub.1, R.sub.2 and R.sub.3 are each independent and represent a hydrogen atom or a phenyl group) are made into fumarates so as to improve their oral absorbability and solubility in water without interfering with their effects.

  具有刺激癌抑制剂的抗癌效果活性的化合物，可以通过以下一般公式（1）表示：##STR1## 其中A是##STR2## （其中R.sub.1、R.sub.2和R.sub.3各自独立地代表氢原子或苯基）被制成富马酸盐，以改善其口服吸收性和水溶性，而不会干扰其效果。
• Treatment of rhinosinusitis with P-glycoprotein inhibitors
  申请人：Massachusetts Eye and Ear Infirmary

  公开号：US10653745B2

  公开（公告）日：2020-05-19

  Provided herein are, inter alia, methods for treating rhinosinusitis with P-glycoprotein inhibitors. A subject having rhinosinusitis is identified and then treated by administration to the subject an effective amount of a P-gp inhibitor. The subject having rhinosinusitis can be identified by one of skill in the art based on known methods, e.g., based on detection of the presence of symptoms, by endoscopy, or by computed tomography. The efficacy of the treatment can be monitored by methods known in the art, e.g., by monitoring symptoms, by endoscopy or computed tomography. The P-glycoprotein inhibitor can be delivered to the subject's nasal passage and sinuses by an inhalation device, by flushing, by spraying, or by an eluting implant surgically placed in the subject's nasal passage or sinuses. The P-glycoprotein inhibitor can also be administered in combination with one or both of a corticosteroid and an antibiotic.

  本文特别提供了用P-糖蛋白抑制剂治疗鼻炎的方法。首先确定患有鼻炎的受试者，然后通过向受试者施用有效量的 P-gp 抑制剂对其进行治疗。本领域技术人员可根据已知的方法，例如根据症状的存在、内窥镜检查或计算机断层扫描，确定患有鼻炎的受试者。治疗的疗效可以通过本领域已知的方法进行监测，例如通过监测症状、内窥镜检查或计算机断层扫描。P-糖蛋白抑制剂可通过吸入装置、冲洗、喷洒或通过手术将洗脱植入物置于受试者的鼻腔或鼻窦中，将其输送到受试者的鼻腔和鼻窦。P 糖蛋白抑制剂还可以与皮质类固醇和抗生素中的一种或两种结合使用。
• Novel ABCA9 transporter and uses thereof
  申请人：Active Pass Pharmaceuticals, Inc.

  公开号：US20020123106A1

  公开（公告）日：2002-09-05

  The invention provides isolated nucleic acid molecules, designated ABCA9 transporter nucleic acid molecules, which encode novel ABC transporter family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing ABCA9 transporter nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which an ABCA9 transporter gene has been introduced or disrupted. The invention further provides isolated ABCA9 transporter proteins, fusion proteins, antigenic peptides, anti-ABCA9 transporter antibodies, and screening assays for ABCA9 transporter modulators. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

  本发明提供了编码新型 ABC 转运体家族成员的分离核酸分子，命名为 ABCA9 转运体核酸分子。本发明还提供了反义核酸分子、含有 ABCA9 转运体核酸分子的重组表达载体、导入表达载体的宿主细胞以及导入或破坏了 ABCA9 转运体基因的非人类转基因动物。本发明进一步提供了分离的 ABCA9 转运体蛋白、融合蛋白、抗原肽、抗 ABCA9 转运体抗体以及 ABCA9 转运体调节剂的筛选测定。还提供了利用本发明组合物的诊断和治疗方法。
• Novel ABCA5 transporter and uses thereof
  申请人：Active Pass Pharmaceuticals, Inc.

  公开号：US20020123107A1

  公开（公告）日：2002-09-05

  The invention provides isolated nucleic acid molecules, designated ABCA5 transporter nucleic acid molecules, which encode novel ABC transporter family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing ABCA5 transporter nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which an ABCA5 transporter gene has been introduced or disrupted. The invention further provides isolated ABCA5 transporter proteins, fusion proteins, antigenic peptides, anti-ABCA5 transporter antibodies, and screening assays for ABCA5 transporter modulators. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

  本发明提供了编码新型 ABC 转运体家族成员的分离核酸分子，命名为 ABCA5 转运体核酸分子。本发明还提供了反义核酸分子、含有 ABCA5 转运体核酸分子的重组表达载体、导入表达载体的宿主细胞以及导入或破坏了 ABCA5 转运体基因的非人类转基因动物。本发明进一步提供了分离的 ABCA5 转运体蛋白、融合蛋白、抗原肽、抗 ABCA5 转运体抗体以及 ABCA5 转运体调节剂的筛选测定。还提供了利用本发明组合物的诊断和治疗方法。