ethyl-2-(4,5-dihydro[1H]imidazol-2-yl)-4-(2-chlorobenzyl)piperazine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl-2-(4,5-dihydro[1H]imidazol-2-yl)-4-(2-chlorobenzyl)piperazine
• 英文别名: 4-[(2-chlorophenyl)methyl]-2-(4,5-dihydro-1H-imidazol-2-yl)-1-ethylpiperazine
• 化学式: C₁₆H₂₃ClN₄
• 分子量: 306.838
• InChiKey: BFXJWYJNXIBEGJ-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：
  0.56
• 拓扑面积：
  30.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氯苄溴 在 三甲基铝 、 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 21.0h， 生成 ethyl-2-(4,5-dihydro[1H]imidazol-2-yl)-4-(2-chlorobenzyl)piperazine
  参考文献：
  名称：

  Design and Synthesis of Imidazoline Derivatives Active on Glucose Homeostasis in a Rat Model of Type II Diabetes. 1. Synthesis and Biological Activities of N-Benzyl-N ‘-(arylalkyl)-2-(4‘,5‘-dihydro-1‘H-imidazol-2‘-yl)piperazines

  摘要：

  The physiopathology of non-insulin-dependent diabetes mellitus is associated with a dysfunction in the regulation of insulin secretion. The alpha(2)-adrenoceptors have been reported to be involved in this alteration, although at-antagonists containing an imidazoline ring may stimulate insulin secretion independently of alpha(2)-adrenoceptor blockage. Recently, a new ''imidazoline-binding site'' involved in the control of K+-ATP channels in the B cell has been proposed. In the course of searching for new antidiabetic agents, 1-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines, 1-benzyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl) and 1-benzyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)-4-benzylpiperazines have been designed and evaluated as potential adrenoceptor antagonists. Pharmacological evaluation was performed in vivo using glucose tolerance tests performed on a rat model of type II diabetes obtained by injection of a low dose (35 mg/kg) of streptozotocin (STZ). For some compounds, binding experiments were performed on alpha(2) adrenoceptors and I-1 and I-2 imidazoline-binding sites. The biological and physicochemical data have been combined with molecular modeling studies to establish structure-activity relationships. The most active compound was 1-(2',4'-dichlorobenzyl)-2 (4',5'-dihydro-1'H-imidazol-2'-yl)-4-methylpiperazine (7f); intraperitoneal administration (100 mu mol/kg) of 7f strongly improved glucose tolerance in STZ diabetic rats. This effect seemed at least partly mediated by a significant increase of insulin secretion. Other compounds of the same family (7b, 16f, 23b) have also shown potent activity. We found no correlation between in vivo antihyperglycemic properties and in vitro affinities for alpha(2)-adrenoceptors or I-1 and I-2 binding sites. These compounds can be considered as antihyperglycemic agents potentially useful for treatment of type II diabetes and are currently under complementary investigation.

  DOI：

  10.1021/jm9608624

文献信息

• Pipérazines substituées, leur procédé de préparation et les compositions pharmaceutiques les contenant
  申请人：ADIR ET COMPAGNIE

  公开号：EP0638568A1

  公开（公告）日：1995-02-15

  Composés de formule générale (I) : dans laquelle A représente le radical X représente N-R₄ ou l'oxygène, et R₁, R₂, R₃, R₄, R₅, n et m sont tels que définis dans la description. Ces composés trouvent leur application en thérapeutique dans le traitement des diabètes non insulino-dépendants.

  通式(I)化合物： 其中 A 代表基团 X 代表 N-R₄ 或氧、 和 R₁、R₂、R₃、R₄、R₅、n 和 m 如说明中所定义。 这些化合物可用于治疗非胰岛素依赖型糖尿病。
• US5492912A
  申请人：——

  公开号：US5492912A

  公开（公告）日：1996-02-20
• US5500426A
  申请人：——

  公开号：US5500426A

  公开（公告）日：1996-03-19
• Design and Synthesis of Imidazoline Derivatives Active on Glucose Homeostasis in a Rat Model of Type II Diabetes. 1. Synthesis and Biological Activities of <i>N</i>-Benzyl-<i>N</i> ‘-(arylalkyl)-2-(4‘,5‘-dihydro-1‘<i>H</i>-imidazol-2‘-yl)piperazines
  作者：Frédéric Rondu、Gaëlle Le Bihan、Xuan Wang、Aazdine Lamouri、Estera Touboul、Georges Dive、Tounès Bellahsene、Bruno Pfeiffer、Pierre Renard、Béatrice Guardiola-Lemaitre、Dominique Manechez、Luc Penicaud、Alain Ktorza、Jean-Jacques Godfroid

  DOI：10.1021/jm9608624

  日期：1997.11.1

  The physiopathology of non-insulin-dependent diabetes mellitus is associated with a dysfunction in the regulation of insulin secretion. The alpha(2)-adrenoceptors have been reported to be involved in this alteration, although at-antagonists containing an imidazoline ring may stimulate insulin secretion independently of alpha(2)-adrenoceptor blockage. Recently, a new ''imidazoline-binding site'' involved in the control of K+-ATP channels in the B cell has been proposed. In the course of searching for new antidiabetic agents, 1-alkyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)piperazines, 1-benzyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl) and 1-benzyl-2-(4',5'-dihydro-1'H-imidazol-2'-yl)-4-benzylpiperazines have been designed and evaluated as potential adrenoceptor antagonists. Pharmacological evaluation was performed in vivo using glucose tolerance tests performed on a rat model of type II diabetes obtained by injection of a low dose (35 mg/kg) of streptozotocin (STZ). For some compounds, binding experiments were performed on alpha(2) adrenoceptors and I-1 and I-2 imidazoline-binding sites. The biological and physicochemical data have been combined with molecular modeling studies to establish structure-activity relationships. The most active compound was 1-(2',4'-dichlorobenzyl)-2 (4',5'-dihydro-1'H-imidazol-2'-yl)-4-methylpiperazine (7f); intraperitoneal administration (100 mu mol/kg) of 7f strongly improved glucose tolerance in STZ diabetic rats. This effect seemed at least partly mediated by a significant increase of insulin secretion. Other compounds of the same family (7b, 16f, 23b) have also shown potent activity. We found no correlation between in vivo antihyperglycemic properties and in vitro affinities for alpha(2)-adrenoceptors or I-1 and I-2 binding sites. These compounds can be considered as antihyperglycemic agents potentially useful for treatment of type II diabetes and are currently under complementary investigation.