tert-butyl {3-[(2-chloropyrimidin-4-yl)amino]propyl}carbamate | 1224600-46-7

• 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: tert-butyl {3-[(2-chloropyrimidin-4-yl)amino]propyl}carbamate
• 英文别名: Tert-butyl (3-((2-chloropyrimidin-4-yl)amino)propyl)carbamate；tert-butyl N-[3-[(2-chloropyrimidin-4-yl)amino]propyl]carbamate
• CAS: 1224600-46-7
• 化学式: C₁₂H₁₉ClN₄O₂
• 分子量: 286.761
• InChiKey: MTGWFNAEGDYVQY-UHFFFAOYSA-N

物化性质

• 沸点：
  492.5±25.0 °C(Predicted)
• 密度：
  1.219±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  76.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl {3-[(2-chloropyrimidin-4-yl)amino]propyl}carbamate 在 caesium carbonate 、 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 2.0h， 生成
  参考文献：
  名称：

  通过模拟戊二酰赖氨酸底物发现新的人类 Sirtuin 5 抑制剂

  摘要：

  人类 sirtuin 5 (SIRT5) 在代谢途径和其他生物过程中起关键作用，并与包括癌症在内的多种人类疾病有关。目前需要开发新的强效和选择性 SIRT5 抑制剂，为相关疾病提供潜在的治疗方法。在这里，我们报告了一系列新的 3-硫脲基丙酸衍生物，这些衍生物旨在模拟 SIRT5 戊二酰赖氨酸底物的结合特征。构效关系研究揭示了几种对 SIRT5 具有低微摩尔抑制活性的化合物。计算和生化研究表明，这些化合物对戊二酰赖氨酸底物而非烟酰胺腺嘌呤二核苷酸辅因子表现出竞争性 SIRT5 抑制作用。而且，他们对 SIRT5 的选择性高于 SIRT1-3 和 6，并且可以稳定 SIRT5 蛋白，如热位移分析所示。这项工作为未来的抑制剂设计提供了一种有效的底物模拟策略，并提供了新的抑制剂来研究它们在 SIRT5 相关疾病模型中的治疗潜力。

  DOI：

  10.1016/j.ejmech.2021.113803
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 11.0h， 生成 tert-butyl {3-[(2-chloropyrimidin-4-yl)amino]propyl}carbamate
  参考文献：
  名称：

  [3H] UR-DEBa176：在人，小鼠和大鼠组胺H4受体上进行2,4-二氨基嘧啶型放射性配体的结合研究。

  摘要：

  人类（h），小鼠（m）和大鼠（r）组胺H4受体（H4R）之间的序列同源性差异会导致配体亲和力，效能和/或效率存在差异，因此会损害翻译动物模型和放射性配体的适用性。针对能够在h / m / rH4Rs上进行稳健和比较结合研究的放射性配体，合成了2,4-二氨基嘧啶并进行了药理研究。鉴定出的最值得注意的化合物是在h / m / rH4R处具有类似效价的两种（部分）激动剂：UR-DEBa148（N-neopentyl-4-（1,4,6,7-tetrahydro-5H-咪唑[4,5 -c] pyridin-5-yl）pyrimidin-2-amine bis（2,2,2-trifluoroacetate），43），最有效的[pEC50（报告基因测定）= 9.9 / 9.6 / 10。3]系列中的化合物略有G蛋白偏置，UR-DEBa176 [[R] -4- [3-（二甲基氨基）吡咯烷丁-1-基] -N-新戊基嘧啶丁-2-胺双（2

  DOI：

  10.1021/acs.jmedchem.9b01342

文献信息

• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2013062945A1

  公开（公告）日：2013-05-02

  The invention is directed to substituted heteroaryl derivatives. Specifically, the invention is directed to compounds according to Formula Q: wherein D, L, M, W, X, Y, and Z are defined herein. The compounds of the invention are inhibitors of DNA methyltransferase (DNMT) activity - including DNMT1, DNMT3a, or DNMT3b - and are useful in the treatment of cancer and hyperproliferative diseases. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及取代的杂芳基衍生物。具体而言，本发明涉及根据公式Q的化合物：其中D、L、M、W、X、Y和Z在此定义。本发明的化合物是DNA甲基转移酶（DNMT）活性的抑制剂，包括DNMT1、DNMT3a或DNMT3b，并且可用于治疗癌症和过度增殖性疾病。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明的化合物或包含本发明化合物的药物组合物来抑制DNMT活性和治疗相关疾病的方法。
• CHEMICAL COMPOUNDS
  申请人：GlaxoSmithKline Intellectual Property (No.2) Limited

  公开号：US20140296204A1

  公开（公告）日：2014-10-02

  The invention is directed to substituted heteroaryl derivatives. Specifically, the invention is directed to compounds according to Formula Q: wherein D, L, M, W, X, Y, and Z are defined herein. The compounds of the invention are inhibitors of DNA methyltransferase (DNMT) activity—including DNMT1, DNMT3a, or DNMT3b—and are useful in the treatment of cancer and hyperproliferative diseases. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及取代杂环基衍生物。具体而言，本发明涉及符合公式Q的化合物：其中D、L、M、W、X、Y和Z在此定义。本发明的化合物是DNA甲基转移酶（DNMT）活性的抑制剂，包括DNMT1、DNMT3a或DNMT3b，并且在癌症和高增殖性疾病的治疗中有用。因此，本发明进一步涉及包含本发明化合物的制药组合物。本发明还涉及使用本发明化合物或包含本发明化合物的制药组合物抑制DNMT活性和治疗与之相关的疾病的方法。
• Discovery of 5-bromo-4-phenoxy-N-phenylpyrimidin-2-amine derivatives as novel ULK1 inhibitors that block autophagy and induce apoptosis in non-small cell lung cancer
  作者：Dejuan Sun、Zijian Yang、Yongqi Zhen、Yushang Yang、Yanmei Chen、Yong Yuan、Lan Zhang、Xiaoxi Zeng、Lixia Chen

  DOI：10.1016/j.ejmech.2020.112782

  日期：2020.12

  UNC51-like kinase1 (ULK1) recruits its binding partners and initiates the autophagy process in cancer. ULK1 is significantly overexpressed in Non-small cell lung cancer (NSCLC) and negatively correlated with clinical prognosis in NSCLC patients. Based upon the binding features of ULK1, we explored the pharmacophore modeling to discover the common anchoring features. It was verified by synthesizing 5-bromo-4-phenoxy-N-phenylpyrimidin-2-amine derivatives, as well as subsequently elucidating the structure-activity relationships (SAR). Among all the obtained ULK1 inhibitors, 5-bromo-4-(2-fluoro-4-nitrophenoxy)-N-(3,4,5-trimethoxyphenyl) pyrimidin-2-amine (3s), was the most active one. The docking analysis was conducted to compare 3s and SBI-0206965, which further elucidated the roles of the H-bond donor. This compound inhibited the proliferation of A549 cells and showed strong inhibitory activity against ULK1 kinase. Moreover, we found that compound 3s could induce apoptosis while simultaneously blocking autophagy. Collectively, these findings shed new light on compound 3s that would be utilized as a promising candidate drug for the future NSCLC therapy.
• Amide-based inhibitors of p38α MAP kinase. Part 2: Design, synthesis and SAR of potent N-pyrimidyl amides
  作者：Richland Tester、Xuefei Tan、Gregory R. Luedtke、Imad Nashashibi、Kurt Schinzel、Weiling Liang、Joon Jung、Sundeep Dugar、Albert Liclican、Jocelyn Tabora、Daniel E. Levy、Steven Do

  DOI：10.1016/j.bmcl.2010.02.090

  日期：2010.4

  Optimization of a tri-substituted N-pyridyl amide led to the discovery of a new class of potent N-pyrimidyl amide based p38 alpha MAP kinase inhibitors. Initial SAR studies led to the identification of 5-dihydrofuran as an optimal hydrophobic group. Additional side chain modi. cations resulted in the introduction of hydrogen bond interactions. Through extensive SAR studies, analogs bearing free amino groups and alternatives to the parent (S)-alpha-methyl benzyl moiety were identified. These compounds exhibited improved cellular activities and maintained balance between p38a and CYP3A4 inhibition. (C) 2010 Elsevier Ltd. All rights reserved.
• US9174984B2
  申请人：——

  公开号：US9174984B2

  公开（公告）日：2015-11-03