5-bromo-2-(4-(methylsulfonyl)benzyloxy)pyridine | 1206968-65-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-bromo-2-(4-(methylsulfonyl)benzyloxy)pyridine
• 英文别名: 5-bromo-2-(4-methanesulfonylbenzyloxy)pyridine；5-bromo-2-[(4-methylsulfonylphenyl)methoxy]pyridine
• CAS: 1206968-65-1
• 化学式: C₁₃H₁₂BrNO₃S
• 分子量: 342.213
• InChiKey: QVVBIPQQOLWYHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  64.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-2-(4-(methylsulfonyl)benzyloxy)pyridine 、 N-Boc-哌嗪 在 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 反应 16.25h， 以43%的产率得到tert-butyl 4-(6-{[4-(methylsulfonyl)benzyl]oxy}pyridin-3-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  Use of Small-Molecule Crystal Structures To Address Solubility in a Novel Series of G Protein Coupled Receptor 119 Agonists: Optimization of a Lead and in Vivo Evaluation

  摘要：

  G protein coupled receptor 119 (GPR119) is viewed as an attractive target for the treatment of type 2 diabetes and other elements of the metabolic syndrome. During a program toward discovering agonists of GPR119, we herein describe optimization of an initial lead compound, 2, into a development candidate, 42. A key challenge in this program of work was the insolubility of the lead compound. Small-molecule crystallography was utilized to understand the intermolecular interactions in the solid state and resulted in a switch from an aryl sulphone to a 3-cyanopyridyl motif. The compound was shown to be effective in wild-type but not knockout animals, confirming that the biological effects were due to GPR119 agonism.

  DOI：

  10.1021/jm300310c
• 作为产物：
  描述：

  2,5-二溴吡啶 、 4-甲砜基苯甲醇 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 5.67h， 以31%的产率得到5-bromo-2-(4-(methylsulfonyl)benzyloxy)pyridine
  参考文献：
  名称：

  GPR119 AGONIST

  摘要：

  公式（II）表示的环胺衍生物是GPR119激动剂，用作治疗糖尿病。其中Ar0是苯或带有取代基如C1-8烷基磺酰基等的苯基，吡啶基，或带有取代基如C1-8烷基磺酰基的吡啶基；A0是（CH2）p，O，或类似物；B0是（CH2）q，或类似物，前提是当A0为O或NR24时，B0既不是O也不是NR25；U0和V0中的一个是N，另一个是N或CR26；X0和Y0中的每一个是C1-3烷基或带有取代基的C1-3烷基；R23是C1-8烷基或类似物；R21和R22中的每一个是氢，卤素原子，或类似物。

  公开号：

  EP2311822A1

文献信息

• GPR119 agonist
  申请人：Endo Tsuyoshi

  公开号：US08536176B2

  公开（公告）日：2013-09-17

  A cyclic amine derivative represented by the formula (II) is a GPR119 agonist, and is used as an agent for treating diabetes. wherein Ar0 is phenyl or phenyl having a substituent such as C1-8 alkylsulfonyl or the like, pyridyl, or pyridyl having a substituent such as C1-8 alkylsulfonyl; A0 is (CH2)p, O, or the like; B0 is (CH2)q, or the like, provided that B0 is neither O nor NR25 when A0 is O or NR24; one of U0 and V0 is N, and the other is N or CR26; each of X0 and Y0 is C1-3 alkylene or C1-3 alkylene having a substituent; R23 is a C1-8 alkyl group or the like; each of R21 and R22 is hydrogen, a halogen atom, or the like.

  公式（II）所表示的环状胺衍生物是GPR119激动剂，可用作治疗糖尿病的药物。其中，Ar0为苯基或带有C1-8烷基磺酰或类似基团的苯基，吡啶基或带有C1-8烷基磺酰或类似基团的吡啶基；A0为（CH2）p，O或类似物；B0为（CH2）q或类似物，但当A0为O或NR24时，B0不能为O或NR25；U0和V0中的一个为N，另一个为N或CR26；X0和Y0中的每一个都是C1-3烷基或带有取代基的C1-3烷基；R23为C1-8烷基或类似物；R21和R22中的每一个都是氢，卤素原子或类似物。
• US8536176B2
  申请人：——

  公开号：US8536176B2

  公开（公告）日：2013-09-17
• GPR119 AGONIST
  申请人：Nippon Chemiphar Co., Ltd.

  公开号：EP2311822A1

  公开（公告）日：2011-04-20

  A cyclic amine derivative represented by the formula (II) is a GPR119 agonist, and is used as an agent for treating diabetes. wherein Ar0 is phenyl or phenyl having a substituent such as C1-8 alkylsulfonyl or the like, pyridyl, or pyridyl having a substituent such as C1-8 alkylsulfonyl; A0 is (CH2)p, O, or the like; B0 is (CH2)q, or the like, provided that B0 is neither O nor NR25 when A0 is O or NR24; one of U0 and V0 is N, and the other is N or CR26; each of X0\ and Y0 is C1-3 alkylene or C1-3 alkylene having a substituent; R23 is a C1-8 alkyl group or the like; each of R21 and R22 is hydrogen, a halogen atom, or the like.

  公式（II）表示的环胺衍生物是GPR119激动剂，用作治疗糖尿病。其中Ar0是苯或带有取代基如C1-8烷基磺酰基等的苯基，吡啶基，或带有取代基如C1-8烷基磺酰基的吡啶基；A0是（CH2）p，O，或类似物；B0是（CH2）q，或类似物，前提是当A0为O或NR24时，B0既不是O也不是NR25；U0和V0中的一个是N，另一个是N或CR26；X0和Y0中的每一个是C1-3烷基或带有取代基的C1-3烷基；R23是C1-8烷基或类似物；R21和R22中的每一个是氢，卤素原子，或类似物。
• Use of Small-Molecule Crystal Structures To Address Solubility in a Novel Series of G Protein Coupled Receptor 119 Agonists: Optimization of a Lead and in Vivo Evaluation
  作者：James S. Scott、Alan M. Birch、Katy J. Brocklehurst、Anders Broo、Hayley S. Brown、Roger J. Butlin、David S. Clarke、Öjvind Davidsson、Anne Ertan、Kristin Goldberg、Sam D. Groombridge、Julian A. Hudson、David Laber、Andrew G. Leach、Philip A. MacFaul、Darren McKerrecher、Adrian Pickup、Paul Schofield、Per H. Svensson、Pernilla Sörme、Joanne Teague

  DOI：10.1021/jm300310c

  日期：2012.6.14

  G protein coupled receptor 119 (GPR119) is viewed as an attractive target for the treatment of type 2 diabetes and other elements of the metabolic syndrome. During a program toward discovering agonists of GPR119, we herein describe optimization of an initial lead compound, 2, into a development candidate, 42. A key challenge in this program of work was the insolubility of the lead compound. Small-molecule crystallography was utilized to understand the intermolecular interactions in the solid state and resulted in a switch from an aryl sulphone to a 3-cyanopyridyl motif. The compound was shown to be effective in wild-type but not knockout animals, confirming that the biological effects were due to GPR119 agonism.