ethyl (R)-1-(2-chloropyrimidin-4-yl)piperidine-3-carboxylate

• 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: ethyl (R)-1-(2-chloropyrimidin-4-yl)piperidine-3-carboxylate
• 英文别名: ethyl (3R)-1-(2-chloropyrimidin-4-yl)piperidine-3-carboxylate
• 化学式: C₁₂H₁₆ClN₃O₂
• 分子量: 269.731
• InChiKey: DIUXQSBPDYQNLE-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  55.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl (R)-1-(2-chloropyrimidin-4-yl)piperidine-3-carboxylate 在 lithium hydroxide monohydrate 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 水 、 二甲基亚砜 、 1,2-二氯乙烷 为溶剂， 生成 (R)-N-(4-methylbenzyl)-1-(2-(3,4,5-trimethoxyphenylamino)pyrimidin-4-yl)piperidine-3-carboxamide
  参考文献：
  名称：

  Rapid Development of Piperidine Carboxamides as Potent and Selective Anaplastic Lymphoma Kinase Inhibitors

  摘要：

  Piperidine carboxamide 1 was identified as a novel inhibitor of anaplastic lymphoma kinase (ALK enzyme assay IC50 = 0.174 mu M) during high throughput screening, with selectivity over the related kinase insulin-like growth factor-1 (IGF1R). The X-ray cocrystal structure of 1 with the ALK kinase domain revealed an unusual DFG-shifted conformation, allowing access to an extended hydrophobic pocket. Structure-activity relationship (SAR) studies were focused on the rapid parallel optimization of both the right- and left-hand side of the molecule, culminating in molecules with improved potency and selectivity over IGF1R.

  DOI：

  10.1021/jm201565s
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 (R)-3-哌啶甲酸乙酯 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以86%的产率得到ethyl (R)-1-(2-chloropyrimidin-4-yl)piperidine-3-carboxylate
  参考文献：
  名称：

  디아실글리세롤 아실트랜스퍼라제 2 억제제로서 유용한 신규 바이아릴 유도체 및 이의 용도

  摘要：

  本发明涉及一种被表示为以下化学式(1)的双芳基衍生物化合物，其表现出抑制二酰基甘油酰转移酶2(DGAT2)活性的能力，以及包含该化合物作为活性成分的药物组合物和其用途：[化学式(1)] 在上述化学式(1)中，A、D、E、R1和R2的定义如说明书所述。

  公开号：

  KR20220031521A

文献信息

• 디아실글리세롤 아실트랜스퍼라제 2 억제제로서 유용한 신규 바이아릴 유도체 및 이의 용도
  申请人：주식회사 엘지화학

  公开号：KR20220031521A

  公开（公告）日：2022-03-11

  본 발명은 디아실글리세롤 아실트랜스퍼라제 2(diacylglycerol acyltransferase 2, DGAT2) 억제제 활성을 나타내는 다음의 화학식 (1)로 표시되는 바이아릴 유도체 화합물, 이를 활성성분으로 포함하는 약제학적 조성물 및 이의 용도에 관한 것이다: [화학식 (1)] 상기 화학식 (1)에서, A, D, E, R 1 및 R 2 는 명세서에서 정의된 바와 같다.

  本发明涉及一种被表示为以下化学式(1)的双芳基衍生物化合物，其表现出抑制二酰基甘油酰转移酶2(DGAT2)活性的能力，以及包含该化合物作为活性成分的药物组合物和其用途：[化学式(1)] 在上述化学式(1)中，A、D、E、R1和R2的定义如说明书所述。
• NOVEL AMINO ARYL DERIVATIVE USEFUL AS DIACYLGLYCEROL ACYLTRANSFERASE 2 INHIBITOR AND USE THEREOF
  申请人：Lg Chem, Ltd.

  公开号：EP4071147A1

  公开（公告）日：2022-10-12

  The present invention relates to an amino aryl derivative compound, represented by chemical formula (1) and exhibiting the activity of a diacylglycerol acyltransferase 2 (DGAT2) inhibitor, a pharmaceutical composition comprising same as an active ingredient, and a use thereof.

  本发明涉及一种氨基苯衍生物化合物，由化学式(1)表示，并表现出二酰基甘油酰基转移酶2(DGAT2)抑制剂的活性，包含该化合物作为活性成分的药剂组合物，以及该化合物的用途。
• Rapid Development of Piperidine Carboxamides as Potent and Selective Anaplastic Lymphoma Kinase Inhibitors
  作者：Marian C. Bryan、Douglas A. Whittington、Elizabeth M. Doherty、James R. Falsey、Alan C. Cheng、Renee Emkey、Rachael L. Brake、Richard T. Lewis

  DOI：10.1021/jm201565s

  日期：2012.2.23

  Piperidine carboxamide 1 was identified as a novel inhibitor of anaplastic lymphoma kinase (ALK enzyme assay IC50 = 0.174 mu M) during high throughput screening, with selectivity over the related kinase insulin-like growth factor-1 (IGF1R). The X-ray cocrystal structure of 1 with the ALK kinase domain revealed an unusual DFG-shifted conformation, allowing access to an extended hydrophobic pocket. Structure-activity relationship (SAR) studies were focused on the rapid parallel optimization of both the right- and left-hand side of the molecule, culminating in molecules with improved potency and selectivity over IGF1R.