1-(1-ethyl-1H-benzimidazol-2-yl)piperazine | 145909-56-4

• 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: 1-(1-ethyl-1H-benzimidazol-2-yl)piperazine
• 英文别名: 1-ethyl-2-(piperazin-1-yl)-1H-benzimidazole；1-ethyl-2-(1-piperazinyl)-1H-benzimidazole；1H-Benzimidazole, 1-ethyl-2-(1-piperazinyl)-；1-ethyl-2-piperazin-1-ylbenzimidazole
• CAS: 145909-56-4
• 化学式: C₁₃H₁₈N₄
• 分子量: 230.313
• InChiKey: LQERTCSWJVMEIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(1-ethyl-1H-benzimidazol-2-yl)piperazine 在 三溴化硼 、 N,N-二异丙基乙胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 {4-[4-(1-Ethyl-1H-benzoimidazol-2-yl)-piperazin-1-yl]-pyrimidin-2-yl}-methanol
  参考文献：
  名称：

  Orally-Effective, Long-Acting Sorbitol Dehydrogenase Inhibitors:  Synthesis, Structure−Activity Relationships, and in Vivo Evaluations of Novel Heterocycle-Substituted Piperazino-Pyrimidines

  摘要：

  Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half-lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED90 less than or equal to 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED90 values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for similar to17 h, when administered orally at a single dose of 2 mg/kg/day.

  DOI：

  10.1021/jm010440g
• 作为产物：
  描述：

  2-氯苯并咪唑 在 sodium hydride 作用下， 反应 2.5h， 生成 1-(1-ethyl-1H-benzimidazol-2-yl)piperazine
  参考文献：
  名称：

  新的2-哌嗪基苯并咪唑衍生物作为5-HT3拮抗剂。合成和药理评价。

  摘要：

  制备了一系列2-哌嗪基苯并咪唑衍生物，并将其评价为5-HT 3受体拮抗剂。通过放射性配体结合测定法评估了它们的5-HT3受体亲和力，并确定了它们在麻醉大鼠中抑制5-HT诱导的Bezold-Jarisch反射的能力。化合物7e（lerisetron，pKi = 9.2）对5-HT3受体的亲和力高于tropisetron和granisetron，而化合物7q（pKi = 7.5）对该受体的亲和力很低，表明苯并咪唑的N1原子被取代环对于亲和力和活性至关重要。还讨论了不同位置的多个取代基对苯并咪唑芳环的取代作用。建立了所研究化合物的5-HT3拮抗活性与芳香环上取代位置的强相关性。因此，尽管4-甲氧基衍生物7m显示出对5-HT 3受体的弱亲和力（pKi ＝ 6.7），但是7-甲氧基衍生物7n显示出最高的亲和力（pKi ＝ 9.4）。化合物7e和7n作为癌症化疗和放疗引起的恶心和呕吐的治疗药物，目前正在进一步研究中。

  DOI：

  10.1021/jm960442e

文献信息

• Substituted piperazine derivatives, the preparation thereofand their use as medicaments
  申请人：——

  公开号：US20030166637A1

  公开（公告）日：2003-09-04

  The present invention relates to substituted piperazine derivatives of general formula 1 , (I wherein R a , R b , R c , R f , R g , X, m and n are defined as in claim 1, the isomers and salts thereof, particularly the physiologically acceptable salts thereof, which are valuable inhibitors of the microsomal triglyceride-transfer protein (MTP), medicaments containing these compounds and their use, as well as the preparation thereof.

  本发明涉及一般式1的取代哌嗪衍生物（I），其中Ra、Rb、Rc、Rf、Rg、X、m和n的定义如权利要求书中所述，其异构体和盐，特别是其生理上可接受的盐，这些盐是微粒体甘油三酯转移蛋白（MTP）的有价值的抑制剂，含有这些化合物的药物以及它们的使用，以及其制备。
• Substituted piperazine derivatives, the preparation thereof and their use as medicaments
  申请人：Boehringer Ingelheim Pharma KG

  公开号：US06821967B2

  公开（公告）日：2004-11-23

  The present invention relates to substituted piperazine derivatives of general formula wherein Ra, Rb, Rc, Rf, Rg, X, m and n are defined as in claim 1, the isomers and salts thereof, particularly the physiologically acceptable salts thereof, which are valuable inhibitors of the microsomal triglyceride-transfer protein (MTP), medicaments containing these compounds and their use, as well as the preparation thereof.

  本发明涉及通式如下的取代哌嗪衍生物： 其中Ra、Rb、Rc、Rf、Rg、X、m和n如权利要求1所定义，其异构体和盐，特别是生理上可接受的盐，是微粒体甘油三酯转移蛋白（MTP）有价值的抑制剂，含有这些化合物的药物以及它们的用途，以及它们的制备。
• New 2-piperazinylbenzimidazole derivatives
  申请人：FABRICA ESPANOLA DE PRODUCTOS QUIMICOS Y FARMACEUTICOS, S.A. (FAES)

  公开号：EP0512939A1

  公开（公告）日：1992-11-11

  A description of new 2-piperazinylbenzimidazole derivatives, of general formula where R can be a hydrogen atom, a short chain alkyl group and a phenyl radical, substituted in position four by a halogen, and R₁ can be a hydrogen atom, an alkoxycarbonyl radical, a hydroxymetyl group and a diphenylmethyl group, and their addition salts with pharmaceutically acceptable acids. these compounds are pharmacologically active as antagonists of serotonin 5HT₃ receptors.

  描述通式为 2-哌嗪基苯并咪唑的新衍生物 其中 R 可以是氢原子、短链烷基和苯基，在第四位被卤素取代，R₁ 可以是氢原子、烷氧羰基、羟甲基和二苯基甲基，以及它们与药学上可接受的酸的加成盐。 这些化合物作为血清素 5HT₃ 受体的拮抗剂具有药理活性。
• 2-piperazinylbenzimidazole derivatives
  申请人：FABRICA ESPANOLA DE PRODUCTOS QUIMICOS Y FARMACEUTICOS, S.A. (FAES)

  公开号：EP0512939B1

  公开（公告）日：1999-08-25
• SUBSTITUIERTE PIPERAZINDERIVATE UND IHRE VERWENDUNG ALS INHIBITOREN DES MIKROSOMALEN TRIGLYZERID-TRANSFERPROTEINS (MTP)
  申请人：Boehringer Ingelheim Pharma KG

  公开号：EP1255736A2

  公开（公告）日：2002-11-13