2-amino-5-(3-methoxyphenyl)pyrimidine | 947592-42-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-amino-5-(3-methoxyphenyl)pyrimidine
• 英文别名: 5-(3-methoxyphenyl)pyrimidin-2-amine
• CAS: 947592-42-9
• 化学式: C₁₁H₁₁N₃O
• 分子量: 201.228
• InChiKey: SUYVTQLOWLCBBF-UHFFFAOYSA-N

物化性质

• 沸点：
  427.1±47.0 °C(Predicted)
• 密度：
  1.201±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  61
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-5-(3-methoxyphenyl)pyrimidine 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 98.25h， 生成 N-ethyl-6-(3-methoxyphenyl)-N-methylimidazo[1,2-a]pyrimidine-2-carboxamide
  参考文献：
  名称：

  Dimroth重排可能是咪唑并[1,2- a ]嘧啶类结构错位的可能原因：一项15 N标记研究和一种确定区域化学的简便方法

  摘要：

  对于复杂的天然产品，经常会出现结构上的错误分配，但这对于看似简单的结构也可能是一个问题。在本文中，我们描述了如何使用15 N标记的类似物确定Dimroth重排可发生在咪唑并[1,2- a ]嘧啶中并导致此类化合物的区域化学错误分配。这些研究支持了包括添加氢氧离子然后开环的重排机制。还观察到，可以使用1 H NMR光谱轻松地区分C（2）和C（3）取代的区域异构体。

  DOI：

  10.1016/j.tet.2018.06.033
• 作为产物：
  描述：

  2-氨基-5-溴嘧啶 、 3-甲氧基苯硼酸 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.25h， 生成 2-amino-5-(3-methoxyphenyl)pyrimidine
  参考文献：
  名称：

  Dimroth重排可能是咪唑并[1,2- a ]嘧啶类结构错位的可能原因：一项15 N标记研究和一种确定区域化学的简便方法

  摘要：

  对于复杂的天然产品，经常会出现结构上的错误分配，但这对于看似简单的结构也可能是一个问题。在本文中，我们描述了如何使用15 N标记的类似物确定Dimroth重排可发生在咪唑并[1,2- a ]嘧啶中并导致此类化合物的区域化学错误分配。这些研究支持了包括添加氢氧离子然后开环的重排机制。还观察到，可以使用1 H NMR光谱轻松地区分C（2）和C（3）取代的区域异构体。

  DOI：

  10.1016/j.tet.2018.06.033

文献信息

• 2-POLYSUBSTITUTED AROMATIC RING-PYRIMIDINE DERIVATIVE AND PREPARATION AND MEDICAL USE
  申请人：Zhejiang University

  公开号：EP3530657A1

  公开（公告）日：2019-08-28

  The present invention provides a 2-polysubstituted aromatic ring-pyrimidine derivative and an optical isomer thereof, or a pharmaceutically acceptable salt or solvate thereof, the compound, and an optical isomer thereof or a pharmaceutically thereof acceptable salts or solvates can be used in the preparation of anti-tumor drugs. The invention designs and synthesizes a series of novel small molecule Chkl inhibitors by using N-substituted pyridin-2-aminopyrimidine obtained by structure-based virtual screening as a lead compound, and carries out Chkl kinase inhibitory activity test. The experiment confirmed that said compounds possess potent anticancer activity, Chkl kinase inhibitory activity, and are promising Chkl inhibitors, and can be used as new cancer therapeutic drugs, which can be applied to treat solid tumors or hematologic tumors related to proliferative disease of human or animal. The 2-polysubstituted aromatic ring-pyrimidine derivatives provided by the present invention has the structure of the formula I:

  本发明提供了一种2-多取代芳环嘧啶衍生物及其光学异构体或其药学上可接受的盐或溶液，该化合物及其光学异构体或其药学上可接受的盐或溶液可用于制备抗肿瘤药物。本发明以基于结构虚拟筛选得到的N-取代吡啶-2-氨基嘧啶为先导化合物，设计合成了一系列新型小分子Chkl抑制剂，并进行了Chkl激酶抑制活性试验。实验证实，上述化合物具有较强的抗癌活性和Chkl激酶抑制活性，是很有前途的Chkl抑制剂，可作为新型肿瘤治疗药物，用于治疗人或动物的实体瘤或与增殖性疾病相关的血液肿瘤。本发明提供的2-多取代芳环嘧啶衍生物具有式I的结构：
• [EN] 2-POLYSUBSTITUTED AROMATIC RING-PYRIMIDINE DERIVATIVE AND PREPARATION AND MEDICAL USE<br/>[FR] DÉRIVÉ PYRIMIDINE À CYCLE AROMATIQUE 2-POLYSUBSTITUÉ ET PRÉPARATION ET UTILISATION MÉDICALE<br/>[ZH] 2-多取代芳环-嘧啶类衍生物及制备和医药用途
  申请人：UNIV ZHEJIANG

  公开号：WO2018086546A1

  公开（公告）日：2018-05-17

  本发明提供一种2-多取代芳环-嘧啶类衍生物及其光学异构体或其药学上可接受的盐或溶剂合物，所述的化合物、及其光学异构体或其药学上可接受的盐或溶剂合物可在制备抗肿瘤药物中的应用。本发明以通过基于结构的虚拟筛选得到的N-取代吡啶-2-氨基嘧啶为先导化合物，设计并合成了一系列全新的小分子Chk1抑制剂，并对该类化合物进行了分子水平的Chk1激酶抑制活性测试。实验证实，所述化合物是一种抗癌作用强，具有Chk1激酶抑制活性，是有前景的Chk1抑制剂，是新的癌症治疗药物，可应用于治疗人或动物细胞增殖性相关的实体瘤或血癌。本发明提供的2-多取代芳环-嘧啶类衍生物具有通式Ⅰ结构：
• Discovery of (R)-5-((5-(1-methyl-1H-pyrazol-4-yl)-4-(methylamino)pyrimidin-2-yl)amino)-3-(piperidin-3-yloxy)picolinonitrile, a novel CHK1 inhibitor for hematologic malignancies
  作者：Lexian Tong、Pinrao Song、Kailong Jiang、Lei Xu、Tingting Jin、Peipei Wang、Xiaobei Hu、Sui Fang、Anhui Gao、Yubo Zhou、Tao Liu、Jia Li、Yongzhou Hu

  DOI：10.1016/j.ejmech.2019.03.062

  日期：2019.7

  Through virtual screening, we identified the lead compound MCL1020, which exhibited modest CHK1 inhibitory activity. Then a series of 5-(pyrimidin-2-ylamino)picolinonitrile derivatives as CHK1 inhibitors were discovered by further rational optimization. One promising molecule. (R)-17, whose potency was one of the best, had an IC50 of 0.4 nM with remarkable selectivity (>4300-fold CHK1 vs. CHK2). Compound (R)-17 effectively inhibited the growth of malignant hematopathy cell lines especially Z-138 (IC50: 0.013 mu M) and displayed low affinity for hERG (IC50> 40 mu M). Moreover, (R)-17 significantly suppressed the tumor growth in Z-138 cell inoculated xenograft model (20 mg/kg I.V., TGI = 90.29%) as a single agent with body weight unaffected. Taken together, our data demonstrated compound (R)-17 could be a promising drug candidate for the treatment of hematologic malignancies. (C) 2019 Published by Elsevier Masson SAS.
• Aryl urea derivatives of spiropiperidines as NPY Y5 receptor antagonists
  作者：Toshiyuki Takahashi、Yuji Haga、Toshihiro Sakamoto、Minoru Moriya、Osamu Okamoto、Katsumasa Nonoshita、Takunobu Shibata、Takuya Suga、Hirobumi Takahashi、Tomoko Hirohashi、Aya Sakuraba、Akira Gomori、Hisashi Iwaasa、Tomoyuki Ohe、Akane Ishihara、Yasuyuki Ishii、Akio Kanatani、Takehiro Fukami

  DOI：10.1016/j.bmcl.2009.05.013

  日期：2009.7

  Continuing medicinal chemistry studies to identify spiropiperidine-derived NPY Y5 receptor antagonists are described. Aryl urea derivatives of a variety of spiropiperidines were tested for their NPY Y5 receptor binding affinities. Of the spiropiperidines so far examined, spiro[3-oxoisobenzofurane-1(3H),4 '-piperidine] was a useful scaffold for producing orally active NPY Y5 receptor antagonists. Oral administration of 5c significantly inhibited the Y5 agonist-induced food intake in rats with a minimum effective dose of 3 mg/kg. In addition, this compound was efficacious in decreasing body weight in diet-induced obese mice. (C) 2009 Elsevier Ltd. All rights reserved.
• 2-polysubstituted aromatic ring-pyrimidine derivatives, preparation and medical application thereof
  申请人：ZHEJIANG UNIVERSITY

  公开号：US20210284625A1

  公开（公告）日：2021-09-16

  The present invention provides a 2-polysubstituted aromatic ring-pyrimidine derivative and an optical isomer thereof, or a pharmaceutically acceptable salt or solvate thereof, the compound, and an optical isomer thereof or a pharmaceutically thereof acceptable salts or solvates can be used in the preparation of anti-tumor drugs. The invention designs and synthesizes a series of novel small molecule Chk1 inhibitors by using N-substituted pyridin-2-aminopyrimidine obtained by structure-based virtual screening as a lead compound, and carries out Chk1 kinase inhibitory activity test. The experiment confirmed that said compounds possess potent anticancer activity, Chk1 kinase inhibitory activity, and are promising Chk1 inhibitors, and can be used as new cancer therapeutic drugs, which can be applied to treat solid tumors or hematologic tumors related to proliferative disease of human or animal. The 2-polysubstituted aromatic ring-pyrimidine derivatives provided by the present invention has the structure of the formula I: