4-[6-(6-methanesulfonyl-2-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester | 1001050-86-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-[6-(6-methanesulfonyl-2-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester
• 英文别名: propan-2-yl 4-[5-methyl-6-[(2-methyl-6-methylsulfonylpyridin-3-yl)amino]pyrimidin-4-yl]oxypiperidine-1-carboxylate
• CAS: 1001050-86-7
• 化学式: C₂₁H₂₉N₅O₅S
• 分子量: 463.558
• InChiKey: BTVNNMSDLVBWRW-UHFFFAOYSA-N

物化性质

• 沸点：
  645.8±55.0 °C(Predicted)
• 密度：
  1.294±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  132
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4,6-二氯-5-甲基嘧啶 在 potassium tert-butylate 、 potassium carbonate 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 4-[6-(6-methanesulfonyl-2-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester
  参考文献：
  名称：

  Discovery of a second generation agonist of the orphan G-protein coupled receptor GPR119 with an improved profile

  摘要：

  The design and synthesis of a second generation GPR119-agonist clinical candidate for the treatment of diabetes is described. Compound 16 (APD597, JNJ-38431055) was selected for preclinical development based on a good balance between agonist potency, intrinsic activity and in particular on its good solubility and reduced drug-drug interaction potential. In addition, extensive in vivo studies showed a more favorable metabolic profile that may avoid the generation of long lasting metabolites with the potential to accumulate in clinical studies. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.092

文献信息

• MODULATORS OF METABOLISM AND THE TREATMENT OF DISORDERS RELATED THERETO
  申请人：Jones Robert M.

  公开号：US20090286816A1

  公开（公告）日：2009-11-19

  The present invention relates to 4-[5-Methoxy-6-(2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester, pharmaceutically acceptable salts, solvates and hydrates thereof that are modulators of glucose metabolism. Accordingly, compounds of the present invention are useful in the treatment of metabolic-related disorders and complications thereof, such as, diabetes and obesity. (Formula I)

  本发明涉及4-[5-甲氧基-6-(2-甲基-6-[1,2,4]三唑-1-基吡啶-3-基氨基)-嘧啶-4-氧基]-哌啶-1-羧酸异丙酯，其药学上可接受的盐、溶剂合物和水合物，它们是葡萄糖代谢调节剂。因此，本发明的化合物在治疗与代谢相关的疾病和并发症方面具有用处，如糖尿病和肥胖。 (化学式 I)
• Modulators of metabolism and the treatment of disorders related thereto
  申请人：Jones Robert M.

  公开号：US20100004272A1

  公开（公告）日：2010-01-07

  The present invention relates to 4-[6-(6-methanesulfonyl-2-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester, pharmaceutically acceptable salts, solvates and hydrates thereof that are modulators of glucose metabolism. Accordingly, compounds of the present invention are useful in the treatment of metabolic-related disorders and complications thereof, such as, diabetes and obesity.

  本发明涉及4-[6-(6-甲烷磺酰基-2-甲基-吡啶-3-基氨基)-5-甲基嘧啶-4-氧基]-哌啶-1-羧酸异丙酯、其药学上可接受的盐、溶剂合物和水合物，这些化合物是葡萄糖代谢调节剂。因此，本发明的化合物在代谢相关疾病及其并发症的治疗中是有用的，如糖尿病和肥胖症。
• WO2008/5576
  申请人：——

  公开号：——

  公开（公告）日：——
• 4-[5-METHOXY-6-(2-METHYL-6-[1,2,4]TRIAZOL-1-YL-PYRIDIN-3-YLAMINO)-PYRIMIDIN-4-YLOXY]-PIPERIDINE-1-CARBOXYLC ACID ISOPROPYL ESTER AS MODULATOR OF METABOLISM AND THE TREATMENT OF DISORDERS RELATED THERETO
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP2051976B1

  公开（公告）日：2010-05-26
• COMBINATION THERAPY FOR THE TREATMENT OF DIABETES AND RELATED CONDITIONS
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2344195A2

  公开（公告）日：2011-07-20