7-(tetrahydro-2H-pyran-4-ylamino)-1,6-naphthyridine-2-carboxylic acid | 1574395-45-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 7-(tetrahydro-2H-pyran-4-ylamino)-1,6-naphthyridine-2-carboxylic acid
• 英文别名: 7-(tetrahydropyran-4-ylamino)-1,6-naphthyridine-2-carboxylic acid；7-(Oxan-4-ylamino)-1,6-naphthyridine-2-carboxylic acid；7-(oxan-4-ylamino)-1,6-naphthyridine-2-carboxylic acid
• CAS: 1574395-45-1
• 化学式: C₁₄H₁₅N₃O₃
• 分子量: 273.291
• InChiKey: YOFSPWHBTDJFEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-(tetrahydro-2H-pyran-4-ylamino)-1,6-naphthyridine-2-carboxylic acid 、 (S)-(3-fluoro-4-methoxyphenyl)(1-methyl-1H-imidazol-5-yl)methanamine hydrochloride 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以69.2%的产率得到(S)-N-((3-fluoro-4-methoxyphenyl)(1-methyl-1H-imidazol-5-yl)methyl)-7-((tetrahydro-2H-pyran-4-yl)amino)-1,6-naphthyridine-2-carboxamide
  参考文献：
  名称：

  SERINE/THREONINE KINASE INHIBITORS

  摘要：

  具有公式I的化合物，其中R2、X和Z如本文所定义，是ERK激酶的抑制剂。还披露了用于治疗过度增殖性疾病的组合物和方法。

  公开号：

  US20140066453A1
• 作为产物：
  描述：

  2-chloro-N-(tetrahydro-2H-pyran-4-yl)-1,6-naphthyridin-7-amine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 20.0~80.0 ℃ 、2.03 MPa 条件下， 反应 6.0h， 生成 7-(tetrahydro-2H-pyran-4-ylamino)-1,6-naphthyridine-2-carboxylic acid
  参考文献：
  名称：

  SERINE/THREONINE KINASE INHIBITORS

  摘要：

  具有公式I的化合物，其中R2、X和Z如本文所定义，是ERK激酶的抑制剂。还披露了用于治疗过度增殖性疾病的组合物和方法。

  公开号：

  US20140066453A1

文献信息

• Discovery of Selective Tertiary Amide Inhibitors of Cyclin-Dependent Kinase 2 (CDK2)
  作者：Mingshuo Zeng、Jessica M. Grandner、Marian C. Bryan、Vishal Verma、Robin Larouche-Gauthier、Jean-Philippe Leclerc、Liang Zhao、Pouyan Haghshenas、Samuel Aubert-Nicol、Arun Yadav、Melissa Ashley、Jacob Z. Chen、Matthew Durk、Karen E. Samy、Marika Nespi、Elizabeth Levy、Karl Merrick、John G. Moffat、Jeremy Murray、Angela Oh、Christine Orr、Ehud Segal、Jessica Sims、Christopher Sneeringer、Madeleine Prangley、Steffan Vartanian、Steven Magnuson、Brendan T. Parr

  DOI：10.1021/acsmedchemlett.3c00142

  日期：2023.9.14

  Cyclin-dependent kinases (CDKs) are key regulators of the cell cycle and are frequently altered in cancer cells, thereby leading to uncontrolled proliferation. In this context, CDK2 has emerged as an appealing target for anticancer drug development. Herein, we describe the discovery of a series of selective small molecule inhibitors of CDK2 beginning with historical compounds from our ERK2 program

  细胞周期蛋白依赖性激酶 (CDK) 是细胞周期的关键调节因子，在癌细胞中经常发生改变，从而导致增殖失控。在此背景下，CDK2 已成为抗癌药物开发的一个有吸引力的靶点。在此，我们描述了一系列选择性 CDK2 小分子抑制剂的发现，从我们的 ERK2 计划中的历史化合物（例如化合物6 ）开始。基于结构的药物设计产生了有效且选择性的工具化合物32 ，其中通过分别填充亲脂性 DFG-1 口袋和靶向与 CDK2 特异性下铰链结合残基的相互作用，实现了对 ERK2 和 CDK4 的优异选择性。化合物32在 OVCAR3 肿瘤小鼠中以 50 mg/kg双剂量(BID) 口服给药显示出 112% 的肿瘤生长抑制作用。
• SERINE/THREONINE KINASE INHIBITORS FOR THE TREATMENT OF HYPERPROLIFERATIVE!DISEASES
  申请人：Array Biopharma, Inc.

  公开号：EP2888247A1

  公开（公告）日：2015-07-01
• SERINE/THREONINE KINASE INHIBITORS FOR THE TREATMENT OF HYPERPROLIFERATIVE DISEASES
  申请人：Array Biopharma, Inc.

  公开号：EP2888247B1

  公开（公告）日：2020-03-25
• ANALOGS AND PRODRUGS OF BUMETANIDE; COMPOSITIONS AND METHODS OF USE
  申请人：HOCHMAN Daryl W.

  公开号：US20140066504A1

  公开（公告）日：2014-03-06

  Novel analogs and prodrugs of the loop diuretic bumetanide are described. Pharmaceutical compositions containing bumetanide analogs and prodrugs are also described. These analogs and prodrugs are particularly useful for the treatment and/or prophylaxis of conditions that involve the NKCC cotransporter family (NKCC1 and NKCC2), or the KCC cotransporter family (KCC1, KCC2, KCC3, KCC4), or GABAa receptors. Such conditions include, but are not limited to anxiety disorders, epilepsy, migraine, non-epileptic seizures, sleep disorders, obesity, eating disorders, autism, depression, edema, glaucoma, stroke, ischemia, neuropathic pain, addictive disorders, schizophrenia, psychosis, and tinnitus.
• ANALOGS AND PRODRUGS OF LOOP DIURETICS, INCLUDING BUMETANIDE, FUROSEMIDE AND PIRETANIDE; COMPOSITIONS AND METHODS OF USE
  申请人：Neuro Pro Therapeutics, Inc.

  公开号：US20150239832A1

  公开（公告）日：2015-08-27

  Novel analogs and prodrugs of the loop diuretics bumetanide, furosemide and piretanide are described. Pharmaceutical compositions containing loop diuretic analogs and prodrugs are also described. These analogs and prodrugs are particularly useful for the treatment and/or prophylaxis of conditions that involve the NKCC cotransporter family (NKCC1 and NKCC2), or the KCC cotransporter family (KCC1, KCC2, KCC3, KCC4), or GABAa receptors. Such conditions include, but are not limited to anxiety disorders, epilepsy, migraine, non-epileptic seizures, sleep disorders, obesity, eating disorders, autism, depression, edema, glaucoma, stroke, ischemia, neuropathic pain, addictive disorders, schizophrenia, psychosis, and tinnitus.