2-ethoxy-4-morpholinoaniline | 761441-14-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 2-ethoxy-4-morpholinoaniline
• 英文别名: 2-Ethoxy-4-(morpholin-4-yl)aniline；2-ethoxy-4-morpholin-4-ylaniline
• CAS: 761441-14-9
• 化学式: C₁₂H₁₈N₂O₂
• 分子量: 222.287
• InChiKey: KGYSUUTWBWYMPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-ethoxy-4-morpholinoaniline 、 2-chloro-N-cyclohexyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine 在 盐酸 、 palladium diacetate 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 1,4-二氧六环 、 甲醇 、 甲苯 为溶剂， 生成 N6-cyclohexyl-N2-[2-ethoxy-4-(morpholin-4-yl)phenyl]-9H-purine-2,6-diamine
  参考文献：
  名称：

  Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors

  摘要：

  Efforts to optimize biological activity, novelty, selectivity and oral bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116 cell line were improved. On-target activity confirmation via mechanism based G2/M escape assay was demonstrated. Physico-chemical and ADME properties were optimized to improve oral bioavailability in mouse. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.131
• 作为产物：
  描述：

  2-乙氧基-4-氟-1-硝基苯 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 生成 2-ethoxy-4-morpholinoaniline
  参考文献：
  名称：

  Lead optimization of purine based orally bioavailable Mps1 (TTK) inhibitors

  摘要：

  Efforts to optimize biological activity, novelty, selectivity and oral bioavailability of Mps1 inhibitors, from a purine based lead MPI-0479605, are described in this Letter. Mps1 biochemical activity and cytotoxicity in HCT-116 cell line were improved. On-target activity confirmation via mechanism based G2/M escape assay was demonstrated. Physico-chemical and ADME properties were optimized to improve oral bioavailability in mouse. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.04.131

文献信息

• Discovery and structure − activity relationship exploration of pyrazolo[1,5-a]pyrimidine derivatives as potent FLT3-ITD inhibitors
  作者：Yun Chen、Gang Bai、Yan Li、Yi Ning、Sufen Cao、Jinpei Zhou、Jian Ding、Huibin Zhang、Hua Xie、Wenhu Duan

  DOI：10.1016/j.bmc.2021.116422

  日期：2021.10

  myeloid leukemia (AML) cases and confer a poor prognosis. Optimization of the screening hit 1 from our in-house compound library led to the discovery of a series of pyrazolo[1,5-a]pyrimidine derivatives as potent and selective FLT3-ITD inhibitors. Compounds 17 and 19 displayed potent FLT3-ITD activities both with IC50 values of 0.4 nM and excellent antiproliferative activities against AML cell lines. Especially

  FLT3 的内部串联重复 (FLT3-ITD) 发生在大约 25% 的所有急性髓性白血病 (AML) 病例中，并且预后不良。我们内部化合物库中筛选命中1的优化导致发现了一系列吡唑并[1,5 - a ]嘧啶衍生物作为有效和选择性的 FLT3-ITD 抑制剂。化合物17和19显示出有效的 FLT3-ITD 活性，IC 50值为 0.4 nM，并且对 AML 细胞系具有优异的抗增殖活性。特别是化合物17和19抑制了 quizartinib 的耐药性—— 赋予突变FLT3 D835Y，两者都具有0.3 nM的IC 50值。此外，蛋白质印迹分析表明化合物17和19有效抑制了 FLT3 的磷酸化并减弱了 AML 细胞中的下游信号传导。这些结果表明吡唑并[1,5 - a ]嘧啶衍生物可能是治疗AML的有前途的FLT3-ITD抑制剂。
• 2, 4-Pyrimidinediamines Useful In The Treatment Of Neoplastic Diseases, Inflammatory And Immune System Disorders
  申请人：Garcia-Echeverria Carlos

  公开号：US20080132504A1

  公开（公告）日：2008-06-05

  Novel pyrimidine derivatives of formula I to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them

  式I的新型嘧啶衍生物及其制备方法，它们的药用价值以及包含它们的药物组合物。
• PYRIMIDINE DERIVATIVES
  申请人：Garcia-Echeverria Carlos

  公开号：US20110201606A1

  公开（公告）日：2011-08-18

  Novel pyrimidine derivatives of formula I to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them

  式I的新型嘧啶衍生物及其制备方法，其用作药物和含有它们的药物组合物。
• 2,4-PYRIMIDINEDIAMINES USEFUL IN THE TREATMENT OF NEOPLASTIC DISEASES, INFLAMMATORY AND IMMUNE SYSTEM DISORDERS
  申请人：Garcia-Echeverria Carlos

  公开号：US20110098280A1

  公开（公告）日：2011-04-28

  Novel pyrimidine derivatives of formula I to processes for their production, their use as pharmaceuticals and to pharmaceutical compositions comprising them.

  I类新型嘧啶衍生物的制备方法，以及它们作为药物和药物组合物的用途。
• Characterization of 2,4-Dianilinopyrimidines Against Five <i>P. falciparum</i> Kinases PfARK1, PfARK3, PfNEK3, PfPK9, and PfPKB
  作者：Han Wee Ong、Chandi de Silva、Krisha Avalani、Frank Kwarcinski、Christopher R. Mansfield、Michael Chirgwin、Anna Truong、Emily R. Derbyshire、Reena Zutshi、David H. Drewry

  DOI：10.1021/acsmedchemlett.3c00354

  日期：2023.12.14

  structure–activity relationship (SAR) campaigns reported. Herein we report the discovery of CZC-54252 (1) as an inhibitor of five P. falciparum kinases PfARK1, PfARK3, PfNEK3, PfPK9, and PfPKB. 39 analogues were evaluated against all five kinases to establish SAR at three regions of the kinase active site. Nanomolar inhibitors of each kinase were discovered. We identified common and divergent SAR trends

  疟原虫激酶越来越被认为是治疗疟疾的潜在新型抗疟原虫靶标，但只有一小部分激酶有结构活性关系（SAR）活动的报道。在此，我们报告了 CZC-54252 ( 1 ) 作为五种恶性疟原虫激酶 PfARK1、PfARK3、PfNEK3、PfPK9 和 PfPKB 抑制剂的发现。针对所有五种激酶评估了 39 种类似物，以在激酶活性位点的三个区域建立 SAR。发现了每种激酶的纳摩尔抑制剂。我们确定了所有五种激酶的共同和不同的 SAR 趋势，突出显示了每个区域中提高每种激酶的效力和选择性的取代基。针对恶性疟原虫血液阶段评估了有效的类似物。发现了八种亚微摩尔抑制剂，其中37 种表现出有效的抗疟原虫活性（EC 50 = 0.16 μM）。我们的结果提供了对抑制每种激酶所需特征的了解，并为未来新型抗疟药的优化工作奠定了基础。