4-[6-(2-fluoro-4-methanesulfonyl-phenylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester | 832755-32-5

• 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-(2-fluoro-4-methanesulfonyl-phenylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester
• 英文别名: 1-Methylethyl 4-[[6-[[2-fluoro-4-(methylsulfonyl)phenyl]amino]-5-methyl-4-pyrimidinyl]oxy]-1-piperidinecarboxylate；propan-2-yl 4-[6-(2-fluoro-4-methylsulfonylanilino)-5-methylpyrimidin-4-yl]oxypiperidine-1-carboxylate
• CAS: 832755-32-5
• 化学式: C₂₁H₂₇FN₄O₅S
• 分子量: 466.534
• InChiKey: CETAULDFJQHIIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  119
• 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-(2-fluoro-4-methanesulfonyl-phenylamino)-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

• [EN] TRISUBSTITUTED ARYL AND HETEROARYL DERIVATIVES AS MODULATORS OF METABOLISM AND THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] DERIVES ARYLES ET HETEROARYLES TRISUBSTITUES UTILISES EN TANT QUE MODULATEURS DU METABOLISME ET PROPHYLAXIE ET TRAITEMENT DE TROUBLES AFFERENTS
  申请人：ARENA PHARM INC

  公开号：WO2005007647A1

  公开（公告）日：2005-01-27

  The present invention relates to certain trisubstituted aryl and heteroaryl derivatives of Formula (I) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

  本发明涉及公式（I）的某些三取代芳基和杂环芳基衍生物，它们是代谢调节剂。因此，本发明的化合物在预防或治疗代谢紊乱及其并发症，如糖尿病和肥胖方面是有用的。
• Trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto
  申请人：Jones M. Robert

  公开号：US20050070562A1

  公开（公告）日：2005-03-31

  The present invention relates to certain trisubstituted aryl and heteroaryl derivatives of Formula (I) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

  本发明涉及公式（I）的某些三取代芳基和杂环芳基衍生物，其是代谢调节剂。因此，本发明的化合物对于预防或治疗代谢性疾病及其并发症（如糖尿病和肥胖症）是有用的。
• Trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the phophylaxis and treatment of disorders related thereto
  申请人：Jones M. Robert

  公开号：US20070155763A1

  公开（公告）日：2007-07-05

  The present invention relates to certain trisubstituted aryl and heteroaryl derivatives of Formula (I) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

  本发明涉及公式（I）的某些三取代芳基和杂环芳基衍生物，它们是代谢调节剂。因此，本发明的化合物在预防或治疗代谢性疾病及其并发症方面是有用的，如糖尿病和肥胖症。
• 1,2,3-TRISUBSTITUTED ARYL AND HETEROARYL DERIVATIVES AS MODULATORS OF METABOLISM AND THE PROPHYLAXIS AND TREATMENT OF DISORDERS RELATED THERETO
  申请人：Jones Robert M.

  公开号：US20110112060A1

  公开（公告）日：2011-05-12

  The present invention relates to certain trisubstituted aryl and heteroaryl derivatives of Formula (I) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

  本发明涉及公式（I）的某些三取代芳基和杂环芳基衍生物，它们是代谢调节剂。因此，本发明的化合物在预防或治疗代谢紊乱及其并发症，如糖尿病和肥胖症方面是有用的。
• Combination therapy for the treatment of diabetes and conditions related thereto and for the treatment of conditions ameliorated by increasing a blood GLP-1 level
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP1808168A1

  公开（公告）日：2007-07-18

  The present invention concerns combination of an amount of a GPR1 19 agonist with an amount of a dipeptidyl peptidase IV (DPP-IV) inhibitor such that the combination provides an effect in lowering a blood glucose level or in increasing a blood GLP-I level in a subject over that provided by the amount of the GPR1 19 agonist or the amount of the DPP-FV inhibitor alone and the use of such a combination for treating or preventing diabetes and conditions related thereto or conditions ameliorated by increasing a blood GLP-I level. The present invention also relates to the use of a G protein-coupled receptor to screen for GLP-I secretagogues.

  本发明涉及一定量的 GPR1 19 激动剂与一定量的二肽基肽酶 IV (DPP-IV) 抑制剂的组合，从而使该组合在降低受试者血糖水平或提高血 GLP-I 水平方面的效果优于单独使用一定量的 GPR1 19 激动剂或 DPP-FV 抑制剂所提供的效果，以及使用这种组合治疗或预防糖尿病及其相关病症或通过提高血 GLP-I 水平而改善的病症。 本发明还涉及使用 G 蛋白偶联受体筛选 GLP-I 促泌剂。