2-methoxy-6-morpholinopyridin-3-amine | 526184-47-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-methoxy-6-morpholinopyridin-3-amine
• 英文别名: 2-methoxy-6-morpholin-4-ylpyridin-3-amine
• CAS: 526184-47-4
• 化学式: C₁₀H₁₅N₃O₂
• 分子量: 209.248
• InChiKey: CMUDOFHQRLSOFU-UHFFFAOYSA-N

物化性质

• 沸点：
  432.9±45.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 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：
  60.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methoxy-6-morpholinopyridin-3-amine 在 sodium hydride 、 碳酸氢钠 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 N-(3-(2-((2-methoxy-6-morpholinopyridin-3-yl)amino)-7-oxo-6-phenylpyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide
  参考文献：
  名称：

  WO2024073745A1

  摘要：

  公开号：
• 作为产物：
  描述：

  2,6-二氯-3-硝基吡啶 在 palladium on activated charcoal 、 氢气 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 mineral oil 为溶剂， 反应 15.0h， 生成 2-methoxy-6-morpholinopyridin-3-amine
  参考文献：
  名称：

  Dual potent ALK and ROS1 inhibitors combating drug-resistant mutants: Synthesis and biological evaluation of aminopyridine-containing diarylaminopyrimidine derivatives

  摘要：

  To identify ALK and ROS1 dual inhibitors conferring resistance to ALK secondary mutations, especially 'gatekeeper' L1196 M and the most predominant ceritinib-resistant G1202R mutations, a series of novel 2,4-diarylaminopyrimidine analogues were designed and synthesized by incorporating 2-alkoxy-6-alicyclic aminopyridinyl motifs. The biological evaluations on cellular and enzymatic assays led to identification of compound F-1, which turned out to be effective against ALK(WT), ROS1(WT), ALK(L1196M) and ALK(G1202R) kinases with IC50 of 2.1 nM, 2.3 nM, 1.3 nM and 3.9 nM, respectively, superior to crizotinib and ceritinib. Moreover, F-1 exhibited significant cytotoxicity on ALK-addicted Karpas299, H2228, and Ba/F3 cell expressing G1202R mutant, as well as ROS1-positive HCC78 cell with IC50 values ranging from 10 nM to 43 nM. Notably, F-1 was capable of suppressing phospho-ALK and its relative downstream signaling pathways, and eventually, inducing cell apoptosis in a dose-dependent manner in Karpas-299 cell. Together, F-1 is validated as a promising ALK/ROS1 dual inhibitor great potential for G1202R ALK mutation cancers. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.09.012

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。
• [EN] INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS
  申请人：CANCER REC TECH LTD

  公开号：WO2014037750A1

  公开（公告）日：2014-03-13

  The present invention relates to compounds of formula (I), wherein R, R, 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。
• 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。
• Identification of Pyridinyltriazine Derivatives as Potent panFGFR Inhibitors against Gatekeeper Mutants for Overcoming Drug Resistance
  作者：SeongShick Ryu、Yunju Nam、Namkyoung Kim、Injae Shin、Eunhye Jeon、Younghoon Kim、Nam Doo Kim、Taebo Sim

  DOI：10.1021/acs.jmedchem.1c01776

  日期：2022.4.28

  various cancers, resistance to the FGFR inhibitors caused by acquired secondary mutations has emerged. To discover novel FGFR inhibitors capable of inhibiting FGFR mutations, including gatekeeper mutations, we designed and synthesized several new pyridinyltriazine derivatives. A structure–activity relationship (SAR) study led to the identification of 17a as a highly potent panFGFR inhibitor against wild-type

  尽管 FGFR 抑制剂有望治疗各种癌症，但已经出现了由获得性二次突变引起的对 FGFR 抑制剂的耐药性。为了发现能够抑制 FGFR 突变（包括看门人突变）的新型 FGFR 抑制剂，我们设计并合成了几种新的吡啶基三嗪衍生物。一项构效关系 (SAR) 研究将17a鉴定为针对野生型和突变型 FGFR 的高效 panFGFR 抑制剂。值得注意的是，17a在激酶抑制和细胞活性方面优于 infigratinib，尤其是针对 V555M-FGFR3。分子动力学模拟清楚地解释了为什么 pyridinyltraizine 衍生物17a具有针对 V555M-FGFR3 的活性。而且，17a通过 FGFR 信号传导阻断、细胞周期停滞和细胞凋亡显着抑制携带 FGFR 突变的癌细胞的增殖。此外，17a和17b在 TEL-V555M-FGFR3 Ba/F3 异种移植小鼠模型中表现出显着的功效，并且17a比 infigratinib
• 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。