tert-butyl 4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)-2,3-dihydrobenzofuran-5-yl)piperazine-1-carboxylate | 1346529-73-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)-2,3-dihydrobenzofuran-5-yl)piperazine-1-carboxylate
• 英文别名: tert-butyl 4-[2-[1-(5-propylpyrimidin-2-yl)piperidin-4-yl]-2,3-dihydro-1-benzofuran-5-yl]piperazine-1-carboxylate
• CAS: 1346529-73-4
• 化学式: C₂₉H₄₁N₅O₃
• 分子量: 507.676
• InChiKey: CKLYJPJPNFDUHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  71
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yl)-2,3-dihydrobenzofuran-5-yl)piperazine-1-carboxylate 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 生成 5-propyl-2-(4-(5-(4-(propylsulfonyl)piperazin-1-yl)-2,3-dihydrobenzofuran-2-yl)piperidin-1-yl)pyrimidine
  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：

  4-(5-bromo-2,3-dihydro-benzofuran-2-yl)-piperidine-1-carboxylic acid tert-butyl ester 在 盐酸 、 potassium tert-butylate 、 potassium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 1,4-二氧六环 、 甲醇 、 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

文献信息

• [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。
• BENZOFURANYL ANALOGUES AS GPR119 MODULATORS
  申请人：Ye Xiang-Yang

  公开号：US20130059858A1

  公开（公告）日：2013-03-07

  Novel compounds of structure Formula I: or an enantiomer, diastereomer, tautomer, prodrug or salt thereof, where-in A, L, m, n, o, p, R 2 , R 3 , R 3 , R 4 and R 5 are defined herein, are provided which are GPR119 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.

  提供结构式I的新型化合物，或其对映体、非对映异构体、互变异构体、前药或盐，其中A、L、m、n、o、p、R2、R3、R4和R5在此定义，这些化合物是GPR119 G蛋白偶联受体调节剂。GPR119 G蛋白偶联受体调节剂可用于治疗、预防或减缓需要GPR119 G蛋白偶联受体调节剂治疗的疾病的进展。因此，本文还涉及包含这些新型化合物的组合物以及使用任何这些新型化合物或包含任何这些新型化合物的组合物治疗与GPR119 G蛋白偶联受体活性相关的疾病或状况的方法。
• Benzofuranyl analogues as GPR119 modulators
  申请人：Ye Xiang-Yang

  公开号：US08729084B2

  公开（公告）日：2014-05-20

  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 GPR119 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.

  提供结构式I的新型化合物，或其对映体、非对映异构体、互变异构体、前药或其盐，其中A、L、m、n、o、p、R2、R3、R3、R4和R5在此定义，这些化合物是GPR119 G蛋白偶联受体调节剂。GPR119 G蛋白偶联受体调节剂在治疗、预防或减缓需要GPR119 G蛋白偶联受体调节剂治疗的疾病方面具有用途。因此，本公开还涉及包含这些新型化合物的组合物以及使用任何这些新型化合物或包含任何这些新型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病症的方法。
• US8729084B2
  申请人：——

  公开号：US8729084B2

  公开（公告）日：2014-05-20