1-(cyclohexylmethyl)-4-<4-<(2,3-dihydro-2-oxo-1H-imidazo<4,5-b>quinolin-7-yl)oxy>-1-oxobutyl>-1-piperazine | 134346-48-8

• 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: 1-(cyclohexylmethyl)-4-<4-<(2,3-dihydro-2-oxo-1H-imidazo<4,5-b>quinolin-7-yl)oxy>-1-oxobutyl>-1-piperazine
• 英文别名: 7-(4-(4-Cyclohexylmethyl)-1-piperazinyl)-4-oxobutoxyl-1,3-dihydro-2H-imidazo(4,5-b)quinolin-2-one；7-[4-[4-(cyclohexylmethyl)piperazin-1-yl]-4-oxobutoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one
• CAS: 134346-48-8
• 化学式: C₂₅H₃₃N₅O₃
• 分子量: 451.569
• InChiKey: KODNKGAUSNMURM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  86.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-Formyl-4-cyclohexylmethylpiperazine 在 4-二甲氨基吡啶 、 sodium hydroxide 、 二苯基磷酸 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 1-(cyclohexylmethyl)-4-<4-<(2,3-dihydro-2-oxo-1H-imidazo<4,5-b>quinolin-7-yl)oxy>-1-oxobutyl>-1-piperazine
  参考文献：
  名称：

  Inhibitors of blood platelet cAMP phosphodiesterase. 3. 1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives with enhanced aqueous solubility

  摘要：

  Two series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives incorporating an additional site for acid salt formation were synthesized and evaluated as inhibitors of human blood platelet cAMP phosphodiesterase (PDE) and ADP-induced platelet aggregation. The objective of this study was to identify compounds that blended potent biological activity with a satisfactory level of aqueous solubility. From a series of 7-aminoimidazo[4,5-b]quinolin-2-ones, biological and physical properties were optimally combined in the 1-piperidinyl derivative 11c. However, this compound offered no significant advantage over earlier studied compounds as an antithrombotic agent in an animal model of small vessel thrombosis. A series of 7-alkoxy alkanoic piperazinamide derivatives, in which the additional basic nitrogen atom was remote from the heterocyclic nucleus and accommodated in a secondary binding region of the cAMP PDE enzyme, demonstrated greater intrinsic cAMP PDE inhibitory activity. Structural modifications of this series focused on variation of the piperazine substituent and side-chain length. The lipophilicity of the N-substituent influenced biological potency and aqueous solubility, with substituents of seven carbon atoms or less generally providing acceptable solubility properties. The N-(cyclohexylmethyl)piperazinamide 21h was identified from this series of compounds as a potent inhibitor of platelet cAMP PDE, IC50 = 0.4 nM, and ADP-induced platelet aggregation, IC50 = 0.51-mu-M after a 3-min exposure and 0.1-mu-M after a 15-min exposure of platelet-rich plasma to the drug. Evaluation of 21h and representative analogues in vivo using a rabbit model of small vessel thrombosis revealed significantly greater antithrombotic efficacy compared to that of previously studied compounds with similar intrinsic biological activity measured in vitro but inferior aqueous solubility.

  DOI：

  10.1021/jm00092a020

文献信息

• MEDICAL MATERIAL AND PROCESS FOR PRODUCING THE SAME
  申请人：OTSUKA PHARMACEUTICAL FACTORY, INC.

  公开号：EP0665023A1

  公开（公告）日：1995-08-02

  A medical material comprising a polymer or copolymer of a polar vinyl derivative and containing an antithrombocytic agent. Since it can release the antithrombocytic agent in an effective concentration for long, it has a high anticoagulant effect and the effect of preventing platelet loss by activating the same.

  一种医用材料，由极性乙烯基衍生物的聚合物或共聚物组成，并含有抗血栓形成剂。由于它能长期释放有效浓度的抗血栓形成剂，因此具有很高的抗凝血效果，并能通过激活血小板防止其流失。
• METHOD OF INHIBITING BLOOD COAGULATION DURING EXTRACORPOREAL BLOOD CIRCULATION AND DEVICE FOR RELEASING ANTITHROMBOTIC DRUG USED THEREIN
  申请人：OTSUKA PHARMACEUTICAL FACTORY, INC.

  公开号：EP0704223A1

  公开（公告）日：1996-04-03

  A method of inhibiting the coagulation of blood during the extracorporeal circulation thereof by bringing a member for releasing an antithrombotic drug, prepared by dispersing a difficulty water-soluble antithrombotic drug in a macromolecular material, into contact with the circulating blood. A device for releasing an antithrombotic drug to be used in the above method comprises either the drug releasing member contained in a vessel provided with blood inlet and outlet ports at the respective ends thereof or the drug releasing member constituting at least the inner wall surface of the vessel. As the antithrombotic agent can be released sustainedly from the drug releasing member, the blood coagulation in the blood circuit can be inhibited as a result of the contact of the blood with the member during the extracorporeal circulation.

  一种在体外循环过程中抑制血液凝固的方法，其方法是将通过在高分子材料中分散难溶于水的抗血栓药物而制备的释放抗血栓药物的部件与循环血液接触。在上述方法中使用的抗血栓药物释放装置包括：药物释放部件装在一个容器中，容器的两端分别设有血液入口和出口；或者药物释放部件至少构成容器的内壁表面。由于抗血栓药物可从药物释放部件中持续释放，在体外循环过程中，血液与该部件的接触可抑制血路中的血液凝固。
• EP0859768A4
  申请人：——

  公开号：EP0859768A4

  公开（公告）日：1998-11-11
• AMINE ACID SALT COMPOUNDS AND PROCESS FOR THE PRODUCTION THEREOF
  申请人：Yoo, Seo Hong

  公开号：EP0859768B1

  公开（公告）日：2003-01-08
• US4943573A
  申请人：——

  公开号：US4943573A

  公开（公告）日：1990-07-24