tert-butyl (2-((2-chloropyrimidin-4-yl)amino)ethyl)carbamate | 849751-45-7

• 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 (2-((2-chloropyrimidin-4-yl)amino)ethyl)carbamate
• 英文别名: tert-Butyl {2-[(2-chloropyrimidin-4-yl)amino]ethyl}carbamate；tert-butyl N-[2-[(2-chloropyrimidin-4-yl)amino]ethyl]carbamate
• CAS: 849751-45-7
• 化学式: C₁₁H₁₇ClN₄O₂
• mdl: MFCD14282061
• 分子量: 272.735
• InChiKey: SHGGSBPPRBPYNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 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 (2-((2-chloropyrimidin-4-yl)amino)ethyl)carbamate 在 氨 作用下， 以 N-甲基吡咯烷酮 为溶剂， 150.0 ℃ 、700.01 kPa 条件下， 反应 72.0h， 以47%的产率得到tert-butyl N-[2-[(2-aminopyrimidin-4-yl)amino]ethyl]carbamate
  参考文献：
  名称：

  Bispyrimidines as Potent Histamine H₄ Receptor Ligands: Delineation of Structure–Activity Relationships and Detailed H₄ Receptor Binding Mode

  摘要：

  The basic methylpiperazine moiety is considered a necessary substructure for high histamine H-4 receptor (H4R) affinity. This moiety is however also the metabolic hot spot for various classes of H4R ligands (e.g., indolcarboxamides and pyrimidines). We set out to investigate whether mildly basic 2-aminopyrimidines in combination with the appropriate linker can serve as a replacement for the methylpiperazine moiety. In the series of 2-aminopyrimidines, the introduction of an additional 2-aminopyrimidine moiety in combination with the appropriate linker lead to bispyrimidines displaying pK(i) values for binding the human H4R up to 8.2. Furthermore, the methylpiperazine replacement results in compounds with improved metabolic properties. The attempt to transfer the knowledge generated in the class of bispyrimidines to the indolecarboxamides failed. Combining the derived structure-activity relationships with homology modeling leads to new detailed insights in the molecular aspects of ligand-H4R binding in general and the binding mode of the described bispyrimidines in specific.

  DOI：

  10.1021/jm301886t
• 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 21.0h， 生成 tert-butyl (2-((2-chloropyrimidin-4-yl)amino)ethyl)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

• FLAP MODULATORS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：US20140221310A1

  公开（公告）日：2014-08-07

  The present invention relates to compounds of Formula (I), or a form thereof, wherein ring A, R 1 , L and R 2 are as defined herein, useful as FLAP modulators. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

  本发明涉及式（I）化合物，或其形式，其中环A，R1，L和R2如本文所定义，作为FLAP调节剂有用。该发明还涉及包含式（I）化合物的药物组合物。制备和使用式（I）化合物的方法也属于本发明的范围。
• [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。
• AMINO-ETHYL-AMINO-ARYL (AEAA) COMPOUNDS AND THEIR USE
  申请人：Raynham Tony Michael

  公开号：US20090247519A1

  公开（公告）日：2009-10-01

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain amino-ethyl-amino-aryl (AEAA) compounds which, inter alia, inhibit protein kinase D (PKD) (e.g., PKD1, PKD2, PKD3). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PKD, and in the treatment of diseases and conditions that are mediated by PKD, that are ameliorated by the inhibition of PKD, etc., including proliferative conditions such as cancer, etc.

  本发明一般涉及治疗化合物领域，更具体地涉及某些氨基乙基氨基芳基（AEAA）化合物，该化合物在抑制蛋白激酶D（PKD）（例如，PKD1、PKD2、PKD3）方面起作用。本发明还涉及包含这些化合物的药物组合物，以及在体外和体内使用这些化合物和组合物来抑制PKD，并用于治疗由PKD介导的疾病和症状，通过抑制PKD而改善的疾病和症状等，包括增殖性疾病如癌症等。
• Heterocyclic amides and sulfonamides
  申请人：Tester Richard

  公开号：US20060199821A1

  公开（公告）日：2006-09-07

  The invention is directed to compounds and methods to inhibit p38 kinase wherein the compounds are a pyrimidine or pyridine coupled to two mandatory substituents.

  本发明涉及一种抑制p38激酶的化合物和方法，其中所述化合物为一种嘧啶或吡啶，与两个必需的取代基相耦合。
• 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。