4-(6-methoxy-5-nitropyridin-2-yl)morpholine | 526184-19-0

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 4-(6-methoxy-5-nitropyridin-2-yl)morpholine
• CAS: 526184-19-0
• 化学式: C₁₀H₁₃N₃O₄
• 分子量: 239.231
• InChiKey: KRVVKFREPYSQKC-UHFFFAOYSA-N

物化性质

• 沸点：
  443.6±45.0 °C(Predicted)
• 密度：
  1.315±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  80.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(6-methoxy-5-nitropyridin-2-yl)morpholine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 5.0h， 生成 N-(2-methoxy-6-morpholinopyridin-3-yl)formamide
  参考文献：
  名称：

  [EN] INHIBITOR COMPOUNDS
  [FR] COMPOSÉS INHIBITEURS

  摘要：

  本发明涉及式(I)的化合物，其中R、R、Ar、W、X和Z均如本文所定义。本发明的化合物已知可以通过直接或间接地与Mps1激酶本身相互作用来抑制单丝粒体1（Mps1，也称为TTK）激酶的纺锤体检查点功能。具体而言，本发明涉及将这些化合物用作治疗和/或预防增殖性疾病，如癌症的治疗剂。本发明还涉及制备这些化合物的方法，以及包含它们的药物组合物。

  公开号：

  WO2014037750A1
• 作为产物：
  描述：

  2,6-二氯-3-硝基吡啶 在 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 6.5h， 生成 4-(6-methoxy-5-nitropyridin-2-yl)morpholine
  参考文献：
  名称：

  Design, synthesis and biological evaluation N2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives bearing acylamino or DBTD ‘head’ as potential ALK inhibitors

  摘要：

  Aiming to develop promising ALK inhibitors, two series of N-2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives (22a-x and 23a-d) were designed according to scaffold hopping and bioisosterism principles. All compounds were efficiently synthesized by concise reactions and anti-proliferative activities on ALK-addicted H2228, Karpas299 cells and EGFR-expressive A549 cell were evaluated by MTT assay. Several compounds exhibited potential cytotoxic activities with IC50 values below 0.10 mu M. Five compounds (22g, 22h, 22l, 22s and 23a) were selected for further enzymatic determination, resulting in the discovery of 22l against ALK and ALK(L1196M) with IC50 values of 2.1 nM and 3.8 nM. Particularly, western blot and cell apoptosis assays identified 22l as a promising ALK inhibitor, which was capable of obviously inhibiting cellular ALK activity and inducing cell apoptosis. Eventually, molecular docking modes of 22l with ALK confirmed structural basis in accordance with the SARs analysis.

  DOI：

  10.1016/j.bioorg.2018.09.019

文献信息

• Design, synthesis and biological evaluation of novel pteridinone derivatives as potent dual inhibitors of PLK1 and BRD4
  作者：Yinliang Qi、Le Xu、Zhiwei Li、Ping Gong、Tao Hu、Bixi Yin、Mingze Qin、Yajing Liu、Yanfang Zhao、Yunlei Hou

  DOI：10.1039/d0nj03477k

  日期：——

  To develop novel simultaneous inhibition of PLK1 and BRD4 bromodomain by a single molecule, three series of novel pteridinone derivatives were designed, synthesized and evaluated for their biological activity. Most compounds exhibited moderate to excellent cytotoxic activity against A549, HCT116, PC-3 and MCF-7 cell lines. The most promising compound III4 showed high antiproliferative effects on four

  为了开发单个分子对PLK1和BRD4溴结构域的新型同时抑制作用，设计，合成和评估了三个系列的新型蝶啶酮衍生物的生物活性。大多数化合物对A549，HCT116，PC-3和MCF-7细胞系表现出中度至优异的细胞毒活性。最有前途的化合物III 4对四种细胞株具有较高的抗增殖作用，IC 50值分别为1.27μM，1.36μM，3.85μM和4.06μM。酶法鉴定为III 4作为有效的PLK1和BRD4双重抑制剂，抑制百分率分别为96.6和59.1。此外，为了阐明目标化合物的抗癌机理，进行了生物活性的探索。结果显示，化合物III 4明显抑制HCT-116细胞系的增殖，诱导线粒体膜电位大大降低，导致癌细胞凋亡，抑制肿瘤细胞迁移，并阻滞HCT116细胞的S期。
• 新型氨基嘧啶类EGFR抑制剂
  申请人：齐鲁制药有限公司

  公开号：CN112538072A

  公开（公告）日：2021-03-23

  本发明提供了作为第四代EGFR(T790M/C797S突变)选择性抑制剂的新型氨基嘧啶类化合物，含有所述化合物的药物组合物、制备所述化合物的有用中间体以及利用本发明化合物治疗细胞增殖性疾病，例如癌症的方法。
• Novel 2,5-diaminopyridine oxidation bases for the dyeing of keratin fibres
  申请人：——

  公开号：US20030163876A1

  公开（公告）日：2003-09-04

  Dyeing compositions for the dyeing of keratin fibres comprising at least one oxidation base chosen from formula (I), as defined herein and addition salts thereof. The use of the compositions for the dyeing of keratin fibres. Dyeing processes employing the compositions. Novel 2,5-diaminopyridine compounds and addition salts thereof and their use as oxidation bases.

  含有至少一种氧化碱的染色组合物，所述氧化碱选择自公式（I）中所定义的氧化碱及其盐。用于染色角蛋白纤维的组合物的使用。采用该组合物的染色过程。新型2,5-二氨基吡啶化合物及其盐以及它们作为氧化碱的用途。
• INHIBITOR COMPOUNDS
  申请人：CANCER RESEARCH TECHNOLOGY

  公开号：US20150239884A1

  公开（公告）日：2015-08-27

  The present invention relates to compounds of formula I wherein R 1 , R 4 , Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及式I的化合物，其中R1、R4、Ar、W、X和Z均如本文所定义。本发明的化合物已知能够直接或间接地通过与Mps1激酶本身的相互作用来抑制单纺锤体1（Mps1，也称为TTK）激酶的纺锤体检查点功能。特别地，本发明涉及使用这些化合物作为治疗和/或预防增生性疾病，如癌症的治疗剂。本发明还涉及制备这些化合物的过程，以及包含它们的药物组合物。
• Inhibitor compounds
  申请人：Cancer Research Technology Limited

  公开号：US09409907B2

  公开（公告）日：2016-08-09

  The present invention relates to compounds of formula I wherein R1, R4, Ar, W, X and Z are all as defined herein. The compounds of the present invention are known to inhibit the spindle checkpoint function of Monospindle 1 (Mps1—also known as TTK) kinases either directly or indirectly via interaction with the Mps1 kinase itself. In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.

  本发明涉及式I的化合物，其中R1、R4、Ar、W、X和Z的定义如本文所述。本发明的化合物已知可以直接或间接地通过与Mps1激酶本身的相互作用来抑制单纺锤体1（Mps1 - 也称为TTK）激酶的纺锤体检查点功能。特别地，本发明涉及使用这些化合物作为治疗和/或预防增生性疾病，如癌症的治疗剂。本发明还涉及制备这些化合物的过程，以及包含它们的药物组合物。