2-氨基-6-(1,1-二甲基丙基)-4,5,6,7-四氢-1-苯并噻吩-3-甲腈 | 329222-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 2-氨基-6-(1,1-二甲基丙基)-4,5,6,7-四氢-1-苯并噻吩-3-甲腈
• 中文别名: 苯并噻吩-3-甲腈,4,5,6,7-四氢-2-氨基-6-(1,1-二甲基丙基)-
• 英文名称: 2-amino-6-(1,1-dimethylpropyl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile
• 英文别名: 2-amino-6-(2-methylbutan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile
• CAS: 329222-98-2
• 化学式: C₁₄H₂₀N₂S
• mdl: MFCD01335783
• 分子量: 248.392
• InChiKey: KWZDWUOSGNGFOU-UHFFFAOYSA-N

物化性质

• 沸点：
  417.0±45.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.642
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2-乙基丁酰氯 、 2-氨基-6-(1,1-二甲基丙基)-4,5,6,7-四氢-1-苯并噻吩-3-甲腈 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以84%的产率得到胰高血糖素受体拮抗剂I
  参考文献：
  名称：

  Direct observation (NMR) of the efficacy of glucagon receptor antagonists in murine liver expressing the human glucagon receptor

  摘要：

  The demonstration of pharmacodynamic efficacy of novel chemical entities represents a formidable challenge in the early exploration of synthetic lead classes. Here, we demonstrate a technique to validate the biological efficacy of novel antagonists of the human glucagon receptor (hGCGR) in the surgically removed perfused liver to the optimization of the pharmacokinetic properties of the compounds. The technique involves the direct observation by (CNMR)-C-13 of the biosynthesis of [C-13]glycogen from [13 C]pyruvate via the gluconeogenic pathway. The rapid breakdown of [13C]glycogen (glycogenolysis) following the addition of if 50 pM exogenous glucagon is then monitored in real time in the perfused liver by C-13 NMR. The concentration-dependent inhibition of glucagon-mediated glycogenolysis is demonstrated for both the peptidyl glucagon receptor antagonist 1 and structurally diverse synthetic antagonists 2-7. Perfused livers were obtained from a transgenic mouse strain that exclusively expresses the functional human glucagon receptor, conferring human relevance to the activity observed with glucagon receptor antagonists. This technique does not provide adequate quantitative precision for the comparative ranking of active compounds, but does afford physiological evidence of efficacy in the early development of a chemical series of antagonists. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.008
• 作为产物：
  描述：

  4-叔丁基环己酮 、 丙二腈 在 吗啉 、 1,2,3,4,5,6,7,8-八硫杂环辛烷 作用下， 以 乙醇 为溶剂， 生成 2-氨基-6-(1,1-二甲基丙基)-4,5,6,7-四氢-1-苯并噻吩-3-甲腈
  参考文献：
  名称：

  Discovery and investigation of a novel class of thiophene-derived antagonists of the human glucagon receptor

  摘要：

  A novel class of antagonists of the human glucagon receptor (bGCGR) has been discovered. Systematic modification of the lead compound identified substituents that were essential for activity and those that were amenable to further optimization. This SAR exploration resulted in the synthesis of 13, which exhibited good potency as an hGCGR functional antagonist (IC50 = 34 nM) and moderate bioavailability (36% in mice). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.01.003

文献信息

• Method of treating diabetes and related conditions
  申请人：Duffy Joseph

  公开号：US20060035958A1

  公开（公告）日：2006-02-16

  The present invention addresses the use of substituted thiophene derivatives, as well as compositions containing such compounds for treating type 2 diabetes mellitus. The compounds in the present invention are glucagon antagonists. The compounds block the action of glucagon at its receptor and thereby decrease the levels of plasma glucose providing a treatment of diabetes.

  本发明涉及使用取代噻吩衍生物以及含有这些化合物的组合物来治疗2型糖尿病。本发明中的化合物是胰高血糖素拮抗剂。这些化合物阻止胰高血糖素在其受体上的作用，从而降低血浆葡萄糖水平，提供糖尿病治疗。
• Cell migration inhibiting compositions and methods and compositions for treating cancer
  申请人：Edwards L. David

  公开号：US20060128742A1

  公开（公告）日：2006-06-15

  Methods for treating an individual having cancer are provided. The method may include administering a cell migration inhibitor and a chemotherapeutic agent to the individual to inhibit migration of cancer cell. Inhibiting cell migration may increase cell division. In this manner, the cell migration inhibitor and the chemotherapeutic agent in combination may have increased efficacy compared to the chemotherapeutic agent alone due to the increased cell division. The cell migration inhibitor may include any of the inhibitors described herein. For example, the cell migration inhibitor may be an organic molecule having a molecular weight of less than about 700, a monoclonal antibody, or a natural product.

  本文提供了治疗癌症患者的方法。该方法可包括向患者施用细胞迁移抑制剂和化疗药物，以抑制癌细胞的迁移。抑制细胞迁移可增加细胞分裂。这样，由于细胞分裂增加，细胞迁移抑制剂和化疗剂联合使用的疗效可能比单独使用化疗剂的疗效更好。细胞迁移抑制剂可包括本文所述的任何抑制剂。例如，细胞迁移抑制剂可以是分子量小于约 700 的有机分子、单克隆抗体或天然产物。
• Discovery and investigation of a novel class of thiophene-derived antagonists of the human glucagon receptor
  作者：Joseph L. Duffy、Brian A. Kirk、Zenon Konteatis、Elizabeth L. Campbell、Rui Liang、Edward J. Brady、Mari Rios Candelore、Victor D.H. Ding、Guoqiang Jiang、Frank Liu、Sajjad A. Qureshi、Richard Saperstein、Deborah Szalkowski、Sharon Tong、Lauri M. Tota、Dan Xie、Xiaodong Yang、Peter Zafian、Song Zheng、Kevin T. Chapman、Bei B. Zhang、James R. Tata

  DOI：10.1016/j.bmcl.2005.01.003

  日期：2005.3

  A novel class of antagonists of the human glucagon receptor (bGCGR) has been discovered. Systematic modification of the lead compound identified substituents that were essential for activity and those that were amenable to further optimization. This SAR exploration resulted in the synthesis of 13, which exhibited good potency as an hGCGR functional antagonist (IC50 = 34 nM) and moderate bioavailability (36% in mice). (c) 2005 Elsevier Ltd. All rights reserved.
• METHOD OF TREATING DIABETES AND RELATED CONDITIONS
  申请人：Merck & Co., Inc.

  公开号：EP1538903A2

  公开（公告）日：2005-06-15
• CELL MIGRATION INHIBITING COMPOSITIONS AND METHODS AND COMPOSITIONS FOR TREATING CANCER
  申请人：Avolix Pharmaceuticals

  公开号：EP1576110A2

  公开（公告）日：2005-09-21