Ethyl 1-benzyl-4-tritylpiperazine-2-carboxylate | 604785-27-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: Ethyl 1-benzyl-4-tritylpiperazine-2-carboxylate
• CAS: 604785-27-5
• 化学式: C₃₃H₃₄N₂O₂
• 分子量: 490.645
• InChiKey: CZBFECJHDRDGAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Ethyl 1-benzyl-4-tritylpiperazine-2-carboxylate 在 盐酸 、 甲酸 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 25.0h， 生成 1-苄基-4-甲基哌嗪-2-羧酸乙酯
  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
• 作为产物：
  描述：

  ethyl 1,4-bis(phenylmethyl)-2-piperazine carboxylate dihydrochloride 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 15.0h， 生成 Ethyl 1-benzyl-4-tritylpiperazine-2-carboxylate
  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

• Piperazinyl-, piperidinyl- and morpholinyl-derivatives as novel inhibitors of histone deacetylase
  申请人：Van Emelen Kristof

  公开号：US20050165016A1

  公开（公告）日：2005-07-28

  This invention comprises the novel compounds of formula (I) wherein t, R 1 , R 2 , L, Q, X, Y, Z and (a) have defined meanings, having histone deacetylase inhibiting enzymatic activity; their preparation, compositions containing them and their use as a medicine.

  本发明包括式 (I) 的新型化合物，其中 t、R 1 , R 2 L, Q, X, Y, Z 和 (a) 具有定义的含义，具有组蛋白去乙酰化酶抑制酶活性；它们的制备、含有它们的组合物及其作为药物的用途。
• PIPERAZINYL-, PIPERIDINYL- AND MORPHOLINYL-DERIVATIVES AS NOVEL INHIBITORS OF HISTONE DEACETYLASE
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1485378A1

  公开（公告）日：2004-12-15
• PIPERAZINYL-, PIPERIDINYL- AND MORPHOLINYL-DERIVATIVES AS NOVEL INHIBITORS OF HISTONE DEACETYLASE
  申请人：EMELEN KRISTOF VAN

  公开号：US20100009988A1

  公开（公告）日：2010-01-14

  This invention comprises the novel compounds of formula (I) wherein t, R 1 , R 2 , L, Q, X, Y, Z and have defined meanings, having histone deacetylase inhibiting enzymatic activity; their preparation, compositions containing them and their use as a medicine.
• US7592450B2
  申请人：——

  公开号：US7592450B2

  公开（公告）日：2009-09-22
• US8501737B2
  申请人：——

  公开号：US8501737B2

  公开（公告）日：2013-08-06