2-[[2-(4-溴苯基)-6-甲基-4-吡啶基]氨基]乙醇 | 330981-72-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-[[2-(4-溴苯基)-6-甲基-4-吡啶基]氨基]乙醇
• 中文别名: 2-((2-(4-溴苯基)-6-甲基嘧啶-4-基)氨基)乙醇
• 英文名称: AS1269574
• 英文别名: 2-{[2-(4-bromophenyl)-6-methylpyrimidin-4-yl]amino}ethanol；GPR119；2-(2-(4-Bromophenyl)-6-methylpyrimidin-4-ylamino)ethanol；2-[[2-(4-bromophenyl)-6-methylpyrimidin-4-yl]amino]ethanol
• CAS: 330981-72-1
• 化学式: C₁₃H₁₄BrN₃O
• 分子量: 308.178
• InChiKey: DUKPGOOUJNUIOI-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  58
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -20℃

制备方法与用途

生物活性

AS1269574 是一种有效的、具有口服活性的 GPR119 激动剂，在表达人 GPR119 的 HEK293 细胞中 EC50 为 2.5 μM。它能够激活 TRPA1 阳离子通道，刺激胰高血糖素样肽-1 (GLP-1) 分泌。在高糖条件下，AS1269574 特异性地诱导胰腺 β 细胞分泌葡萄糖依赖性胰岛素。该化合物在 2 型糖尿病研究中具有潜在价值。

靶点

| TRPA1 | GPR119 |

体内研究

AS1269574 显著降低了口服给药后两小时的血糖 AUC（AUC_0-2h）。实验结果显示，8 周龄 ICR 小鼠在给予 100 mg/kg 的 AS1269574 后，两小时内血糖 AUC 显著降低。同时，血浆胰岛素 AUC_0-2h 也显著升高。

反应信息

• 作为产物：
  描述：

  4-溴苯甲脒盐酸盐水合物 在 sodium methylate 、 三氯氧磷 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 22.67h， 生成 2-[[2-(4-溴苯基)-6-甲基-4-吡啶基]氨基]乙醇
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 4-amino-2-phenylpyrimidine derivatives as a series of novel GPR119 agonists

  摘要：

  Through preparation and examination of a series of novel 4-amino-2-phenylpyrimidine derivatives as agonists for GPR119, we identified 2-(4-bromophenyl)-6-methyl-N-[2-(1-oxidopyridin-3-yl)ethyl]pyrimidin-4-amine (9t). Compound 9t improved glucose tolerance in mice following oral administration and showed good pharmacokinetic profiles in rats. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2012.02.006

文献信息

• Use of GPR119 receptor agonists for increasing bone mass and for treating osteoporosis, as well as combination therapy relating thereto
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP2253311A2

  公开（公告）日：2010-11-24

  The present invention relates to the use of GPR119 receptor agonists for treating or preventing a condition characterized by low bone mass, such as osteoporosis, and for increasing bone mass in an individual. The present invention further relates to the use of a GPR119 receptor agonist in combination with a dipeptidyl peptidase IV (DPP-IV) inhibitor for treating or preventing a condition characterized by low bone mass, such as osteoporosis, and for increasing bone mass in an individual. A GPR119 receptor agonist and the combination of a GPR119 receptor agonist and a DPP-IV inhibitor promote bone formation in an individual.

  本发明涉及 GPR119 受体激动剂用于治疗或预防以低骨量为特征的疾病，如骨质疏松症，以及用于增加个体的骨量。本发明进一步涉及 GPR119 受体激动剂与二肽基肽酶 IV (DPP-IV) 抑制剂联合用于治疗或预防以低骨量为特征的疾病，如骨质疏松症，以及增加个体的骨量。GPR119 受体激动剂以及 GPR119 受体激动剂与 DPP-IV 抑制剂的组合可促进个体的骨形成。
• USE OF GPR119 RECEPTOR AGONISTS FOR INCREASING BONE MASS AND FOR TREATING OSTEOPOROSIS, AS WELL AS COMBINATION THERAPY RELATING THERETO
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP2004157B1

  公开（公告）日：2011-01-12
• GPR119 receptor agonists in methods of increasing bone mass and of treating osteoporosis and other conditions characterized by low bone mass, and combination therapy relating thereto
  申请人：Chu Zhi-Liang

  公开号：US20090270422A1

  公开（公告）日：2009-10-29

  The present invention relates to the use of GPR119 receptor agonists for treating or preventing a condition characterized by low bone mass, such as osteoporosis, and for increasing bone mass in an individual. The present invention further relates to the use of a GPR119 receptor agonist in combination with a dipeptidyl peptidase IV (DPP-IV) inhibitor for treating or preventing a condition characterized by low bone mass, such as osteoporosis, and for increasing bone mass in an individual. A GPR119 receptor agonist and the combination of a GPR119 receptor agonist and a DPP-IV inhibitor promote bone formation in an individual.
• GPR119 Receptor Agonists in Methods of Increasing Bone Mass and of Treating Osteoporosis and Other Conditions Characterized by Low Bone Mass, and Combination Therapy Relating Thereto
  申请人：Chu Zhi-Liang

  公开号：US20100190750A1

  公开（公告）日：2010-07-29

  The present invention relates to the use of GPR119 receptor agonists for treating or preventing a condition characterized by low bone mass, such as osteoporosis, and for increasing bone mass in an individual. The present invention further relates to the use of a GPR119 receptor agonist in combination with a dipeptidyl peptidase IV (DPP-IV) inhibitor for treating or preventing a condition characterized by low bone mass, such as osteoporosis, and for increasing bone mass in an individual. A GPR119 receptor agonist and the combination of a GPR119 receptor agonist and a DPP-IV inhibitor promote bone formation in an individual.
• US7816364B2
  申请人：——

  公开号：US7816364B2

  公开（公告）日：2010-10-19