4,5-二氯-6-甲基嘧啶-2-胺 | 7749-60-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4,5-二氯-6-甲基嘧啶-2-胺
• 英文名称: 4,5-dichloro-6-methylpyrimidin-2-amine
• CAS: 7749-60-2
• 化学式: C₅H₅Cl₂N₃
• mdl: MFCD00244693
• 分子量: 178.021
• InChiKey: JQAJPNDZWOIYFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  正丁胺 、 4,5-二氯-6-甲基嘧啶-2-胺 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 12.0h， 以79%的产率得到N4-butyl-5-chloro-6-methylpyrimidine-2,4-diamine
  参考文献：
  名称：

  Human Toll-like Receptor (TLR) 8-Specific Agonistic Activity in Substituted Pyrimidine-2,4-diamines

  摘要：

  Activation of human toll-like receptor-8 (TLR8) evokes a distinct cytokine profile favoring the generation of Type 1 helper T cells. A multiplexed high-throughput screen had led to the identification of N-4-butyl-5-iodo-6-methylpyrimidine-2,4-diamine as a pure TLR8 agonist, and a detailed structure-activity relationship study of this chemotype was undertaken. A butyl substituent at N-4 was optimal, and replacement of the 5-iodo group with chloro, bromo, or fluoro groups led to losses in potency, as did the introduction of aromatic bulk. Drawing from our previous structure-based design, several 5-alkylamino derivatives were evaluated. Significant enhancement of potency was achieved in 5-(4-aminobutyl)-N-4-butyl-6-methylpyrimidine-2,4-diamine. This compound potently induced Th1-biasing IFN-gamma And IL-12 in human blood, but lower levels of the proinflammatory cytokines IL-1 beta, IL-6, and IL-8. These results suggest that the inflammatory and reactogenic propensities of this compound could be considerably more favorable than other TLR8 agonists under evaluation.

  DOI：

  10.1021/acs.jmedchem.6b00872
• 作为产物：
  描述：

  2-氨基-4-氯-6-甲基嘧啶 在 N-氯代丁二酰亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以71%的产率得到4,5-二氯-6-甲基嘧啶-2-胺
  参考文献：
  名称：

  PYRIMIDINES AND USES THEREOF

  摘要：

  本文提供的各种示例是针对下述公式的化合物的：其中R1-R5在此处被定义，并且这些化合物的用途包括在其他方面抑制受试者的免疫反应。

  公开号：

  US20180215720A1

文献信息

• PYRIMIDINES AND USES THEREOF
  申请人：David Sunil Abraham

  公开号：US20180215720A1

  公开（公告）日：2018-08-02

  The various examples presented herein are directed to compounds of the Formula: wherein R 1 -R 5 are defined herein, and uses of such compounds to, among other things, inhibit an immune response in a subject.

  本文提供的各种示例是针对下述公式的化合物的：其中R1-R5在此处被定义，并且这些化合物的用途包括在其他方面抑制受试者的免疫反应。
• [EN] INHIBITORS OF PHOSPHOINOSITIDE 3-KINASE AND HISTONE DEACETYLASE FOR TREATMENT OF CANCER<br/>[FR] INHIBITEURS DE LA PHOSPHOINOSITIDE 3-KINASE ET DE L'HISTONE DÉSACÉTYLASE POUR LE TRAITEMENT DU CANCER
  申请人：US HEALTH

  公开号：WO2018237007A1

  公开（公告）日：2018-12-27

  The present invention is directed to a dual inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC), including a core containing a quinazoline moiety or a quinazolin-4(3H)-one moiety, a kinase hinge binding moiety, and a histone deacetylase pharmacophore, a pharmaceutically acceptable salt thereof, a prodrug thereof, or solvate thereof. The present invention is also directed to a histone deacetylase inhibitor, including a core containing a quinazolin-4(3H)-one moiety and a histone deacetylase pharmacophore.

  本发明涉及一种磷脂酰肌醇3-激酶（PI3K）和组蛋白去乙酰化酶（HDAC）的双重抑制剂，包括一个含有喹唑啉基团或喹唑啉-4(3H)-酮基团的核心，一个激酶铰链结合基团，和一个组蛋白去乙酰化酶药效团，以及其药用盐、前药或溶剂化物。本发明还涉及一种组蛋白去乙酰化酶抑制剂，包括一个含有喹唑啉-4(3H)-酮基团和一个组蛋白去乙酰化酶药效团的核心。
• Design, Synthesis, and Biological Evaluation of Quinazolin-4-one-Based Hydroxamic Acids as Dual PI3K/HDAC Inhibitors
  作者：Ashish Thakur、Gregory J. Tawa、Mark J. Henderson、Carina Danchik、Suiyang Liu、Pranav Shah、Amy Q. Wang、Garrett Dunn、Md Kabir、Elias C. Padilha、Xin Xu、Anton Simeonov、Surender Kharbanda、Richard Stone、Gurmit Grewal

  DOI：10.1021/acs.jmedchem.0c00193

  日期：2020.4.23

  quinazolin-4-one based hydroxamic acids was rationally designed and synthesized as novel dual PI3K/HDAC inhibitors by incorporating an HDAC pharmacophore into a PI3K inhibitor (Idelalisib) via an optimized linker. Several of these dual inhibitors were highly potent (IC50 < 10 nM) and selective against PI3Kγ, δ and HDAC6 enzymes and exhibited good antiproliferative activity against multiple cancer cell lines

  通过经由优化的接头将HDAC药效团掺入PI3K抑制剂（Idelalisib）中，合理设计和合成了一系列基于喹唑啉-4-酮的异羟肟酸，作为新型的双重PI3K / HDAC抑制剂。这些双重抑制剂中的几种非常有效（IC50 <10 nM），对PI3Kγ，δ和HDAC6酶具有选择性，并且对多种癌细胞具有良好的抗增殖活性。铅化合物48c在AML患者的几种突变型和FLT3抗性AML细胞系和原代细胞中诱导坏死，而对正常PBMC，NIH3T3和HEK293细胞无细胞毒性。使用细胞热位移分析（CETSA）在MV411细胞中证明了48c的PI3Kδ和HDAC6的靶标结合。
• Pyrimidines and uses thereof
  申请人：Regents of the University of Minnesota

  公开号：US10662161B2

  公开（公告）日：2020-05-26

  The various examples presented herein are directed to compounds of the Formula: wherein R1-R5 are defined herein, and uses of such compounds to, among other things, inhibit an immune response in a subject.

  本文介绍的各种示例均针对式化合物： 其中 R1-R5 在本文中定义，以及此类化合物在抑制受试者免疫反应等方面的用途。
• INHIBITORS OF PHOSPHOINOSITIDE 3-KINASE AND HISTONE DEACETYLASE FOR TREATMENT OF CANCER
  申请人：THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVIC

  公开号：US20200165257A1

  公开（公告）日：2020-05-28

  The present invention is directed to a dual inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC), including a core containing a quinazoline moiety or a quinazolin-4(3H)-one moiety, a kinase hinge binding moiety, and a histone deacetylase pharmacophore, a pharmaceutically acceptable salt thereof, a prodrug thereof, or solvate thereof. The present invention is also directed to a histone deacetylase inhibitor, including a core containing a quinazolin-4(3H)-one moiety and a histone deacetylase pharmacophore.