t-Butyl 2-(4-amino-2-fluoro-phenyl)-pyrrole-1-carboxylate | 859538-05-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: t-Butyl 2-(4-amino-2-fluoro-phenyl)-pyrrole-1-carboxylate
• 英文别名: tert-butyl 2-(4-amino-2-fluorophenyl)pyrrole-1-carboxylate
• CAS: 859538-05-9
• 化学式: C₁₅H₁₇FN₂O₂
• 分子量: 276.311
• InChiKey: WWOVAMWWBLSTGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  t-Butyl 2-(4-amino-2-fluoro-phenyl)-pyrrole-1-carboxylate 在 platinum on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 以85%的产率得到t-Butyl 2-(4-amino-2-fluoro-phenyl)-pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Discovery of novel 2-(pyridine-2-yl)-1H-benzimidazole derivatives as potent glucokinase activators

  摘要：

  The synthesis and structure-activity-relationships (SARs) of novel 2-(pyridine-2-yl)-1H-benzimidazole glucokinase activators are described. Systematic modi. cation of benzimidazole lead 5a identified from a high-throughput screening led to the discovery of a potent and metabolically stable glucokinase activator 16p(R) with greater structural diversity from GKAs reported to date. The compound also demonstrated acute oral glucose lowering efficacy in rat OGTT model. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.038
• 作为产物：
  描述：

  4-溴-3-氟苯胺 、 1-Boc-吡咯-2-硼酸 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 以63%的产率得到t-Butyl 2-(4-amino-2-fluoro-phenyl)-pyrrole-1-carboxylate
  参考文献：
  名称：

  Discovery of novel 2-(pyridine-2-yl)-1H-benzimidazole derivatives as potent glucokinase activators

  摘要：

  The synthesis and structure-activity-relationships (SARs) of novel 2-(pyridine-2-yl)-1H-benzimidazole glucokinase activators are described. Systematic modi. cation of benzimidazole lead 5a identified from a high-throughput screening led to the discovery of a potent and metabolically stable glucokinase activator 16p(R) with greater structural diversity from GKAs reported to date. The compound also demonstrated acute oral glucose lowering efficacy in rat OGTT model. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.05.038

文献信息

• Novel 2-Heteroaryl-Substituted Benzimidazole Derivative
  申请人：Nonoshita Katsumasa

  公开号：US20080070928A1

  公开（公告）日：2008-03-20

  A glucokinase activator is provided; and a remedy and/or a preventive for diabetes, or a remedy and/or a preventive for diabetes such as retinopathy, nephropathy, neurosis, ischemic cardiopathy, arteriosclerosis, and further a remedy and/or a preventive for obesity are provided. A glucokinase activator characterized by containing a 2-heteroaryl-substituted benzimidazole derivative of a general formula (I-0) or its pharmaceutically-acceptable salt: [in the formula, X represents a carbon atom or a nitrogen atom; X 1 , X 2 , X 3 and X 4 each independently represent a carbon atom or a nitrogen atom; the ring A represents a 5- or 6-membered nitrogen-containing aromatic hetero ring of a formula (II): (in the formula, X represents a carbon atom or a nitrogen atom); R 1 represents an aryl, etc.; R 2 represents a hydroxy, etc.; R 3 represents a —C 1-6 alkyl, etc.; R 4 represents a —C 1-6 alkyl, etc.; X 5 represents —O—, etc.; a indicates an integer of 1, 2 or 3; q indicates an integer of from 0 to 2; m indicates an integer of from 0 to 2].

  提供了一种葡萄糖激酶激活剂；提供了糖尿病的治疗和/或预防，或者提供了糖尿病的治疗和/或预防，例如视网膜病变、肾病、神经病、缺血性心脏病、动脉硬化，以及肥胖症的治疗和/或预防。葡萄糖激酶激活剂的特征在于包含通式（I-0）的2-杂环芳基取代苯并咪唑衍生物或其药学上可接受的盐：[在公式中，X表示碳原子或氮原子；X1、X2、X3和X4分别独立地表示碳原子或氮原子；环A表示公式（II）的5-或6-成员含氮芳香杂环：（在公式中，X表示碳原子或氮原子）；R1表示芳基等；R2表示羟基等；R3表示-C1-6烷基等；R4表示-C1-6烷基等；X5表示-O-等；a表示1、2或3的整数；q表示0到2的整数；m表示0到2的整数]。
• 2-heteroaryl-substituted benzimidazole derivative
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US07728025B2

  公开（公告）日：2010-06-01

  A glucokinase activator is provided; and a remedy and/or a preventive for diabetes, or a remedy and/or a preventive for diabetes such as retinopathy, nephropathy, neurosis, ischemic cardiopathy, arteriosclerosis, and further a remedy and/or a preventive for obesity are provided. A glucokinase activator characterized by containing a 2-heteroaryl-substituted benzimidazole derivative of a general formula (I-0) or its pharmaceutically-acceptable salt: [in the formula, X represents a carbon atom or a nitrogen atom; X1, X2, X3 and X4 each independently represent a carbon atom or a nitrogen atom; the ring A represents a 5- or 6-membered nitrogen-containing aromatic hetero ring of a formula (II): (in the formula, X represents a carbon atom or a nitrogen atom); R1 represents an aryl, etc.; R2 represents a hydroxy, etc.; R3 represents a —C1-6 alkyl, etc.; R4 represents a —C1-6 alkyl, etc.; X5 represents —O—, etc.; a indicates an integer of 1, 2 or 3; q indicates an integer of from 0 to 2; m indicates an integer of from 0 to 2].

  提供了一种葡萄糖激酶激活剂；提供了糖尿病的治疗和/或预防，或类似视网膜病变、肾病、神经病、缺血性心脏病、动脉硬化等糖尿病的治疗和/或预防，以及肥胖症的治疗和/或预防。一种葡萄糖激酶激活剂，其特征在于包含一般式（I-0）的2-杂环芳基取代苯并咪唑衍生物或其药学上可接受的盐：[在该式中，X表示碳原子或氮原子；X1、X2、X3和X4各自独立地表示碳原子或氮原子；环A表示式（II）的5-或6-成员含氮芳杂环：（在该式中，X表示碳原子或氮原子）；R1表示芳基等；R2表示羟基等；R3表示- C1-6烷基等；R4表示- C1-6烷基等；X5表示-O-等；a表示1、2或3的整数；q表示0到2的整数；m表示0到2的整数。
• NOVEL 2-HETEROARYL-SUBSTITUTED BENZIMIDAZOLE DERIVATIVE
  申请人：MSD K.K.

  公开号：EP1702919B1

  公开（公告）日：2012-05-30
• US7728025B2
  申请人：——

  公开号：US7728025B2

  公开（公告）日：2010-06-01
• Discovery of novel 2-(pyridine-2-yl)-1H-benzimidazole derivatives as potent glucokinase activators
  作者：Makoto Ishikawa、Katsumasa Nonoshita、Yoshio Ogino、Yoshikazu Nagae、Daisuke Tsukahara、Hideka Hosaka、Hiroko Maruki、Sumika Ohyama、Riki Yoshimoto、Kaori Sasaki、Yasufumi Nagata、Jun-ichi Eiki、Teruyuki Nishimura

  DOI：10.1016/j.bmcl.2009.05.038

  日期：2009.8

  The synthesis and structure-activity-relationships (SARs) of novel 2-(pyridine-2-yl)-1H-benzimidazole glucokinase activators are described. Systematic modi. cation of benzimidazole lead 5a identified from a high-throughput screening led to the discovery of a potent and metabolically stable glucokinase activator 16p(R) with greater structural diversity from GKAs reported to date. The compound also demonstrated acute oral glucose lowering efficacy in rat OGTT model. (C) 2009 Elsevier Ltd. All rights reserved.