2,3-二甲基异烟酸甲酯 | 1254328-26-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2,3-二甲基异烟酸甲酯
• 英文名称: methyl 2,3-dimethylisonicotinate
• 英文别名: methyl 2,3-dimethylpyridine-4-carboxylate
• CAS: 1254328-26-1
• 化学式: C₉H₁₁NO₂
• 分子量: 165.192
• InChiKey: CDALNXGJTOUCHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3-二甲基异烟酸甲酯 在 platinum(IV) oxide 、 氢气 作用下， 以 溶剂黄146 为溶剂， 50.0 ℃ 、5.0 MPa 条件下， 反应 18.0h， 以77%的产率得到(+/-)-(2R,3R,4R)-methyl 2,3-dimethylpiperidine-4-carboxylate
  参考文献：
  名称：

  Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization

  摘要：

  We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.

  DOI：

  10.1021/jm1008727
• 作为产物：
  描述：

  4,5-二甲基噁唑 、 丙烯酸甲酯（MA） 在 对苯二酚 作用下， 以 苯 为溶剂， 反应 18.0h， 以44%的产率得到2,3-二甲基异烟酸甲酯
  参考文献：
  名称：

  Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: SAR and Structural Characterization

  摘要：

  We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.

  DOI：

  10.1021/jm1008727

文献信息

• [EN] 6,7-DIHYDROPYRAZOLO[1,5-A]PYRAZIN-4(5H)-ONE COMPOUNDS AND THEIR USE AS NEGATIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS<br/>[FR] COMPOSÉS 6,7-DIHYDROPYRAZOLO[1,5-A] PYRAZIN-4(5H)-ONE ET LEUR UTILISATION COMME MODULATEURS ALLOSTÉRIQUES NÉGATIFS DES RÉCEPTEURS MGLUR2
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2016016395A1

  公开（公告）日：2016-02-04

  The present invention relates to novel 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 2 ("mGluR2"). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention or treatment of disorders in which the mGluR2 subtype of metabotropic receptors is involved.

  本发明涉及新型的6,7-二氢吡唑[1,5-a]吡嗪-4(5H)-酮衍生物，作为代谢型谷氨酸受体2型("mGluR2")的负变构调节剂(NAMs)。该发明还涉及包含这些化合物的药物组合物，制备这些化合物和组合物的方法，以及使用这些化合物和组合物预防或治疗涉及代谢型受体mGluR2亚型的疾病。
• 8-ANILINOIMIDAZOPYRIDINES AND THEIR USE AS ANTI-CANCER AND/OR ANTI-INFLAMMATORY AGENTS
  申请人：Price Stephen

  公开号：US20100280063A1

  公开（公告）日：2010-11-04

  The invention relates to imidazopyridines of formula I with anti-cancer and/or anti-inflammatory activity and more specifically to imidazopyridines which inhibit MEK kinase activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth or treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

  本发明涉及公式I的咪唑吡啶，具有抗癌和/或抗炎活性，更具体地涉及抑制MEK激酶活性的咪唑吡啶。本发明提供了用于抑制异常细胞生长或治疗哺乳动物的增殖性疾病或治疗炎症性疾病的组合物和方法。本发明还涉及使用化合物进行哺乳动物细胞的体外、体内诊断或治疗，或相关的病理条件的方法。
• Substituted 6,7-dihydropyrazolo[1,5-a] pyrazines as negative allosteric modulators of mGlUR2 receptors
  申请人：Janssen Pharmaceutica NV

  公开号：US10005785B2

  公开（公告）日：2018-06-26

  The present invention relates to novel 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives of Formula (I) as negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 2 (“mGluR2”). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention or treatment of disorders in which the mGluR2 subtype of metabotropic receptors is involved.

  本发明涉及式 (I) 的新型 6,7-二氢吡唑并[1,5-a]吡嗪-4(5H)-酮衍生物 作为代谢型谷氨酸受体亚型 2（"mGluR2"）的负异位调节剂（NAMs）。本发明还涉及包含此类化合物的药物组合物、制备此类化合物和组合物的工艺，以及使用此类化合物和组合物预防或治疗涉及代谢型受体 mGluR2 亚型的疾病。
• 6,7-DIHYDROPYRAZOLO[1,5-a]PYRAZIN-4(5H)-ONE COMPOUNDS AND THEIR USE AS NEGATIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
  申请人：Janssen Pharmaceutica NV

  公开号：US20170217971A1

  公开（公告）日：2017-08-03

  The present invention relates to novel 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 2 (“mGluR2”). The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention or treatment of disorders in which the mGluR2 subtype of metabotropic receptors is involved.
• US8293763B2
  申请人：——

  公开号：US8293763B2

  公开（公告）日：2012-10-23