2-chloro-4-(4-methoxyphenoxy)-5-nitropyrimidine | 1297931-00-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-chloro-4-(4-methoxyphenoxy)-5-nitropyrimidine
• CAS: 1297931-00-0
• 化学式: C₁₁H₈ClN₃O₄
• 分子量: 281.655
• InChiKey: GESUVVANQSGVSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  90.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(4-methoxyphenoxy)-5-nitropyrimidine 在 铁粉 sodium hydroxide 、 二氯甲烷 、 水 、 Brine 、 Sodium sulfate-III 作用下， 以 溶剂黄146 、 甲醇 为溶剂， 反应 2.5h， 以Concentration of the mixture gave Compound 8b (0.49 g; 100%)的产率得到2-chloro-4-(4-methoxy-phenoxy)-pyrimidin-5-ylamine
  参考文献：
  名称：

  PHENOXY-SUBSTITUTED PYRIMIDINES AS OPIOID RECEPTOR MODULATORS

  摘要：

  本发明涉及化合物、组合物和治疗各种疾病、综合征、状况和障碍的方法，包括疼痛。此类化合物由以下式子I表示：其中R1、Y、R2、R3和Ra在此定义。

  公开号：

  US20140066422A1
• 作为产物：
  描述：

  4-甲氧基苯酚 、 2,4-二氯-5 硝基嘧啶 在 碳酸氢钠 作用下， 以 水 、 丙酮 为溶剂， 反应 2.0h， 以89%的产率得到2-chloro-4-(4-methoxyphenoxy)-5-nitropyrimidine
  参考文献：
  名称：

  基于苯氧嘧啶骨架的新型LCK / FMS抑制剂可潜在治疗炎性疾病

  摘要：

  酪氨酸激酶（包括LCK和FMS）参与炎症性疾病以及许多类型的癌症。我们的团队已经设计和合成了30种针对LCK的新型基于嘧啶的抑制剂，分为四种不同的系列（酰胺，脲，亚胺（席夫碱）和苄胺）。其中十二个显示出纳摩尔IC 50值。化合物7g表现出出色的选择性，对FMS激酶具有选择性（IC 50值4.6 nM）。进行了分子对接研究，以帮助我们合理化所获得的结果并预测我们的化合物在LCK和FMS中的可能结合方式。基于获得的生物测定数据和建模结果，讨论了详细的SAR研究。作为有关新化合物抗炎作用的进一步测试，对RAW 264.7巨噬细胞进行了体外细胞测定。化合物7g显示出优异的抗炎作用。因此，我们报告了新型苯氧基嘧啶衍生物作为强效和选择性LCK抑制剂的设计，以及7g作为强效和选择性FMS / LCK双重抑制剂的发现，可潜在地应用于包括类风湿性关节炎（RA）在内的炎性疾病。

  DOI：

  10.1016/j.ejmech.2017.10.003

文献信息

• PYRIMIDINE COMPOUNDS AS DELTA OPIOID RECEPTOR MODULATORS
  申请人：COATS STEVEN J.

  公开号：US20110105520A1

  公开（公告）日：2011-05-05

  Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula I as follows: wherein R 1 , R 2 , R 3 , and L, A, and R a are defined herein.

  公开了用于治疗各种疾病、综合征、状况和失调，包括疼痛的化合物、组合物和方法。这些化合物由以下式I表示： 其中R1、R2、R3和L、A、Ra在本文中定义。
• First-in-class DAPK1/CSF1R dual inhibitors: Discovery of 3,5-dimethoxy-N-(4-(4-methoxyphenoxy)-2-((6-morpholinopyridin-3-yl)amino)pyrimidin-5-yl)benzamide as a potential anti-tauopathies agent
  作者：Ahmed Karam Farag、Ahmed H.E. Hassan、Hyeanjeong Jeong、Youngji Kwon、Jin Gyu Choi、Myung Sook Oh、Ki Duk Park、Yun Kyung Kim、Eun Joo Roh

  DOI：10.1016/j.ejmech.2018.10.057

  日期：2019.1

  Compound 3l, the most potent DAPK1 inhibitor in the in vitro kinase assay (IC50 = 1.25 μM) was the most effective tau aggregates formation inhibitor in the cellular assay (IC50 = 5.0 μM). Also, compound 3l elicited potent inhibition of CSF1R in the in vitro kinase assay (IC50 = 0.15 μM) and promising inhibition of nitric oxide production in LPS-induced BV-2 cells (55% inhibition at 10 μM concentration)

  激酶异常与几种复杂的神经退行性疾病有关。这些激酶的选择性抑制剂的开发可能会提供有希望的抗tauopathy疗法。DAPK1抑制剂可以阻止tau聚集物的形成并抵消神经元的死亡，而CSF1R抑制剂可以减轻与陶氏病相关的神经炎症。在这里，我们报告新型CSF1R / DAPK1双重抑制剂作为多功能分子抑制tau聚集体的形成和神经炎症的设计，合成，生物学评估，机理研究和分子对接研究。化合物3l是体外激酶测定中最有效的DAPK1抑制剂（IC 50 = 1.25μM）是细胞测定中最有效的tau聚集体形成抑制剂（IC 50  = 5.0μM）。而且，化合物3l在体外激酶测定中引起对CSF1R的有效抑制（IC 50  = 0.15μM），并有望抑制LPS诱导的BV-2细胞中一氧化氮的产生（在10μM浓度下抑制55％）。激酶谱分析和hERG结合测定法预计不会出现脱靶毒性，而PAMPA-BBB测定法则预测可能具
• Pyrimidine compounds as delta opioid receptor modulators
  申请人：Janssen Pharmaceutica, NV

  公开号：US08685990B2

  公开（公告）日：2014-04-01

  Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula I as follows: wherein R1, R2, R3, and L, A, and Ra are defined herein.

  本发明揭示了化合物、组合物和治疗各种疾病、综合征、病况和障碍的方法，包括疼痛。这些化合物由以下式子I所表示：其中R1、R2、R3以及L、A和Ra在此定义。
• Diarylurea derivatives comprising 2,4-diarylpyrimidines: Discovery of novel potential anticancer agents via combined failed-ligands repurposing and molecular hybridization approaches
  作者：Ahmed Karam Farag、Ahmed H.E. Hassan、Kyung-Sook Chung、Jeong-Hun Lee、Hyo-Sun Gil、Kyung-Tae Lee、Eun Joo Roh

  DOI：10.1016/j.bioorg.2020.104121

  日期：2020.10

  A series of diarylurea derivatives comprising 2,4-diarylpyrimidines were synthesized based on a combination of postulated molecular hybridization design and failed-ligands repurposing approaches, which enabled the discovery of novel potential antiproliferative agents. Towards credible biological evaluation, an in vitro anticancer activity assay was conducted employing a library of 60 cancer cell lines constituting nine panels representing blood, lung, colon, CNS, skin, ovary, renal, prostate, and breast cancers. The results revealed high effectiveness and broad-spectrum anticancer activity of compounds 4m and 4g. Five-dose assay of compounds 4m and 4g proved their high potency that surpassed that of four standard kinase inhibitors FDA-approved anticancer drugs against many cancer cells. Towards the identification of their molecular target, screening of kinase inhibitory profile employing a panel of 51 kinases involved in cancer revealed inhibition of several kinases from the platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) kinase family, which might mediate, at least in part, the antiproliferative activity. Molecular docking of 4g into the crystal structure of the Feline McDonough Sarcoma (FMS) kinase predicted that it binds to a pocket formed by the juxtamembrane domain, the catalytic loop, and the aE helix, thus stabilizing the inhibited conformation of the kinase. Flow cytometric study of the cytotoxic effects of compound 4g in A549 cells showed it induces dose- and timedependent apoptotic events leading to cell death. Collectively, this work presents compound 4g as a potential broad-spectrum anticancer agent against multiple cancer types.
• EGFR inhibitors from cancer to inflammation: Discovery of 4-fluoro-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide as a novel anti-inflammatory EGFR inhibitor
  作者：Ahmed Elkamhawy、Ahmed H.E. Hassan、Sora Paik、Yong Sup Lee、Hwi-Ho Lee、Ji-Sun Shin、Kyung-Tae Lee、Eun Joo Roh

  DOI：10.1016/j.bioorg.2019.01.017

  日期：2019.5

  EGFR inhibitors are well-known as anticancer agents. Quite differently, we report our effort to develop EGFR inhibitors as anti-inflammatory agents. Pyrimidinamide EGFR inhibitors eliciting low micromolar IC50 and the structurally close non-EGFR inhibitor urea analog were synthesized. Comparing their nitric oxide (NO) production inhibitory activity in peritoneal macrophages and RAW 246.7 macrophages indicated that their anti-inflammatory activity in peritoneal macrophages might be a sequence of EGFR inhibition. Further evaluations proved that compound 4d significantly and dose-dependently inhibits LPS-induced iNOS expression and IL-1 beta, IL-6, and TNF-alpha production via NF-kappa B inactivation in peritoneal macrophages. Compound 4d might serve as a lead compound for development of a novel class of anti-inflammatory EGFR inhibitors.