4-(5-bromo-2,3-dihydro-benzofuran-2-yl)-piperidine | 1346529-71-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: 4-(5-bromo-2,3-dihydro-benzofuran-2-yl)-piperidine
• 英文别名: 4-(5-Bromo-2,3-dihydrobenzofuran-2-yl)piperidine；4-(5-bromo-2,3-dihydro-1-benzofuran-2-yl)piperidine
• CAS: 1346529-71-2
• 化学式: C₁₃H₁₆BrNO
• 分子量: 282.18
• InChiKey: RQJZGBQAZQWOOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(5-bromo-2,3-dihydro-benzofuran-2-yl)-piperidine 在 potassium tert-butylate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 12.0h， 生成 tert-butyl 4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)-2,3-dihydrobenzofuran-5-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  Synthesis and structure–activity relationship of dihydrobenzofuran derivatives as novel human GPR119 agonists

  摘要：

  Through appropriate medicinal chemistry design tactics and computer-assisted conformational modeling, the initial lead A was evolved into a series of dihydrobenzofuran derivatives 3 as potent GPR119 agonists. This Letter describes the optimization of general structure 3, including the substituent(s) on dihydrobenzofuran, the R-1 attachment on right-hand piperidine nitrogen, and the left-hand piperidine/piperazine and its attachment R-2. The efforts led to the identification of compounds 13c and 24 as potent human GPR119 modulators with favorable metabolic stability, ion channel activity, and PXR profiles. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.096
• 作为产物：
  描述：

  2,3-苯并呋喃 在 盐酸 、 三乙基硅烷 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， -78.0~40.0 ℃ 、379.22 kPa 条件下， 反应 0.33h， 生成 4-(5-bromo-2,3-dihydro-benzofuran-2-yl)-piperidine
  参考文献：
  名称：

  Synthesis and structure–activity relationship of dihydrobenzofuran derivatives as novel human GPR119 agonists

  摘要：

  Through appropriate medicinal chemistry design tactics and computer-assisted conformational modeling, the initial lead A was evolved into a series of dihydrobenzofuran derivatives 3 as potent GPR119 agonists. This Letter describes the optimization of general structure 3, including the substituent(s) on dihydrobenzofuran, the R-1 attachment on right-hand piperidine nitrogen, and the left-hand piperidine/piperazine and its attachment R-2. The efforts led to the identification of compounds 13c and 24 as potent human GPR119 modulators with favorable metabolic stability, ion channel activity, and PXR profiles. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.096

文献信息

• [EN] FUSED DIHYDROFURANS AS GPR119 MODULATORS FOR THE TREATMENT OF DIABETES, OBESITY AND RELATED DISORDERS<br/>[FR] DIHYDROFURANES CONDENSÉS EN TANT QUE MODULATEURS DE GPR119 POUR LE TRAITEMENT DU DIABÈTE, DE L'OBÉSITÉ ET DE TROUBLES ASSOCIÉS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012098217A1

  公开（公告）日：2012-07-26

  The present invention relates to compounds of general formula (I), wherein the groups R1, LP, LQ, X1, X2, X3, A, n and m are as defined in the application, which have valuable pharmacological properties, and in particular bind to the GPR119 receptor and modulate its activity.

  本发明涉及一般式(I)的化合物，其中基团R1、LP、LQ、X1、X2、X3、A、n和m如申请中所定义，具有有价值的药理特性，特别是结合到GPR119受体并调节其活性。
• [EN] FUSED DIHYDROPYRANS AS GPR119 MODULATORS FOR THE TREATMENT OF DIABETES, OBESITY AND RELATED DISEASES<br/>[FR] DIHYDROPYRANNES FONDUS UTILISÉS COMME MODULATEURS DE GPR119 POUR TRAITER LE DIABÈTE, L'OBÉSITÉ ET LES MALADIES ASSOCIÉES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012080476A1

  公开（公告）日：2012-06-21

  The present invention relates to compounds of general formula (I), wherein the groups R1, LP, LQ, X1, X2, X3, Ar and n are as defined in the application, which have valuable pharmacological properties, and in particular bind to the GPR119 receptor and modulate its activity.

  本发明涉及一般式（I）的化合物，其中基团R1、LP、LQ、X1、X2、X3、Ar和n如申请中所定义，具有有价值的药理特性，特别是结合到GPR119受体并调节其活性。
• Compounds, pharmaceutical compositions and uses thereof
  申请人：HIMMELSBACH Frank

  公开号：US20120322784A1

  公开（公告）日：2012-12-20

  The present invention relates to compounds of formula I, wherein the groups R 1 , L P , L Q , X 1 , X 2 , X 3 , Ar and n are as defined in the application, which have valuable pharmacological properties, and in particular bind to the GPR119 receptor and modulate its activity.

  本发明涉及公式I的化合物， 其中R 1 ，LP，LQ，X 1 ，X 2 ，X 3 ，Ar和n的定义如申请中所述，具有有价值的药理特性，特别是结合GPR119受体并调节其活性。
• New compounds, pharmaceutical compositions and uses thereof
  申请人：HIMMELSBACH Frank

  公开号：US20130018030A1

  公开（公告）日：2013-01-17

  The present invention relates to compounds of general formula I, wherein the groups R 1 , L P , L Q , X 1 , X 2 , X 3 , A, n and m are as defined in the application. The compounds of formula I have valuable pharmacological properties, and in particular bind to the GPR119 receptor and modulate its activity.

  本发明涉及一般式I的化合物， 其中基团R 1 ，L P ，L Q ，X 1 ，X 2 ，X 3 ，A，n和m如申请中所定义。公式I的化合物具有有价值的药理特性，特别是结合到GPR119受体并调节其活性。
• [EN] BENZOFURANYL ANALOGUES AS GPR119 MODULATORS<br/>[FR] ANALOGUES DE BENZOFURANYLE EN TANT QUE MODULATEURS DE GPR119
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2011140161A1

  公开（公告）日：2011-11-10

  Novel compounds of structure Formula I: or an enantiomer, diastereomer, tautomer, prodrug or salt thereof, wherein A, L, m, n, o, p, R2, R3, R3, R4 and R5 are defined herein, are provided which are GPR1 19 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.

  结构式I的新化合物：或其对映体、二对映体、互变异构体、前药或盐，其中A、L、m、n、o、p、R2、R3、R3、R4和R5在此处定义，在此提供了作为GPR1 19 G蛋白偶联受体调节剂的化合物。GPR119 G蛋白偶联受体调节剂对于治疗、预防或减缓需要GPR119 G蛋白偶联受体调节剂治疗的疾病是有用的。因此，该公开还涉及包含这些新化合物的组合物和使用任何这些新化合物或含有任何这些新化合物的组合物来治疗与GPR119 G蛋白偶联受体活性相关的疾病或症状的方法。