2,4-dichloro-6-ethylphenylpyrimidine | 656822-36-5

• 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: 2,4-dichloro-6-ethylphenylpyrimidine
• 英文别名: 2,4-dichloro-6-phenethyl-pyrimidine；2,4-Dichloro-6-phenethylpyrimidine；2,4-dichloro-6-(2-phenylethyl)pyrimidine
• CAS: 656822-36-5
• 化学式: C₁₂H₁₀Cl₂N₂
• 分子量: 253.131
• InChiKey: LQROXLLINZAYQB-UHFFFAOYSA-N

物化性质

• 沸点：
  346.8±27.0 °C(Predicted)
• 密度：
  1.309±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  异丁硫醇 、 2,4-dichloro-6-ethylphenylpyrimidine 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 16.5h， 以92%的产率得到2,4-bis-isobutylsulfanyl-6-phenethyl-pyrimidine
  参考文献：
  名称：

  Blocking Estrogen Signaling After the Hormone: Pyrimidine-Core Inhibitors of Estrogen Receptor-Coactivator Binding

  摘要：

  As an alternative approach to blocking estrogen action, we have developed small molecules that directly disrupt the key estrogen receptor (ER)/coactivator interaction necessary for gene activation. The more direct, protein-protein nature of this disruption might be effective even in hormone-refractory breast cancer. We have synthesized a pyrimidine-core library of moderate size, members of which act as a-helix mimics to block the ER alpha/coactivator interaction. Structure-activity relationships have been explored with various C-, N-, O-, and S-substituents on the pyrimidine core. Time-resolved fluorescence resonance energy transfer and cell-based reporter gene assays show that the most active members inhibit the ER alpha/steroid receptor coactivator interaction with Ki's in the low micromolar range. Through these studies, we have obtained a refined pharmacophore model for activity in this pyrimidine series. Furthermore, the favorable activities of several of these compounds support the feasibility that this coactivator binding inhibition mechanism for blocking estrogen action might provide a potential alternative approach to endocrine therapy.

  DOI：

  10.1021/jm800698b
• 作为产物：
  描述：

  3-氧代-5-苯基-戊酸乙酯 在 potassium carbonate 、 氯乙酸 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 生成 2,4-dichloro-6-ethylphenylpyrimidine
  参考文献：
  名称：

  设计，合成和体外生物学评估雌激素受体α共激活因子结合的小分子抑制剂。

  摘要：

  与激动剂配体复合的核受体（NRs）通过募集共激活蛋白复合物来激活转录。原则上，应该使用适当设计的共激活因子结合抑制剂（CBI）直接阻止这种转录关键受体-共激活因子的相互作用，从而抑制NRs的转录活性。为了指导我们各种CBI的设计，我们使用了激动剂结合的雌激素受体（ER）配体结合结构域（LBD）的晶体结构，该结构与含有LXXLL签名基元并结合到表面疏水槽的助活化剂肽复合的LBD。一组基于从外而内的设计方法的CBI，具有各种杂环核心（三氮烯，嘧啶，三硫杂环己烷，环己烷），它们模仿肽螺旋上三个亮氨酸的系链位点，在其上连接有亮氨酸残基样取代基。另一组基于“由内而外”的方法，具有一个萘核，该萘核模拟两个最深埋的亮氨酸，其取代基向外延伸，以模拟共活化剂螺旋肽的其他特征。开发了一种基于荧光各向异性的共激活剂竞争测定法，以测量这些CBI与ER激动剂复合物与共激活剂相互作用的凹槽位点的特异性结合。对照配体结

  DOI：

  10.1021/jm030404c

文献信息

• Pyrimidine derivatives as IL-8 receptor antagonists
  申请人：——

  公开号：US20040087601A1

  公开（公告）日：2004-05-06

  Compounds containing the pyrimidine nucleus and their use to treat diseases and conditions related to inappropriate Interleukin-8 receptor activity are disclosed. The compounds are of the formula I 1 In these compounds, Q is preferably unsubstituted and substituted heterocyclyl; U is usually hydrogen or fluorine; and V is preferably hydrogen, halogen, alkyl, —O—alkyl or —S-alkyl. A representative example is: 2

  含有嘧啶核的化合物及其用于治疗与不适当的白细胞介素-8受体活性相关的疾病和症状的用途已被披露。这些化合物的结构式为I 1 在这些化合物中，Q最好是未取代或取代的杂环烷基；U通常是氢或氟；V最好是氢、卤素、烷基、—O—烷基或—S-烷基。一个代表性的例子是： 2
• US7037916B2
  申请人：——

  公开号：US7037916B2

  公开（公告）日：2006-05-02
• [EN] PYRIMIDINE DERIVATIVES AS IL-8 RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE PYRIMIDINE UTILISES COMME ANTAGONISTES DES RECEPTEURS DE L'IL-8
  申请人：PHARMACOPEIA INC

  公开号：WO2004062609A2

  公开（公告）日：2004-07-29

  Compounds containing the pyrimidine nucleus and their use to treat diseases and conditions related to inappropriate Interleukin-8 receptor activity are disclosed. The compounds are of the formula (I). In these compounds, Q is preferably unsubstituted and substituted heterocyclyl; U is usually hydrogen or fluorine; and V is preferably hydrogen, halogen, alkyl, -O-alkyl or -S-alkyl. A representative example is formula (X).
• [EN] DIAMINOPYRIMIDINE DERIVATIVES AND PROCESSES FOR THE PREPARATION THEREOF<br/>[FR] DÉRIVÉS DE DIAMINOPYRIMIDINE ET LEURS PROCÉDÉS DE PRÉPARATION
  申请人：YUHAN CORP

  公开号：WO2012115479A2

  公开（公告）日：2012-08-30

  The present invention provides a diaminopyrimidine derivative or its pharmaceutically acceptable salt, a process for the preparation thereof, a pharmaceutical composition comprising the same, and a use thereof. The diaminopyrimidine derivative or its pharmaceutically acceptable salt functions as a 5-HT4 receptor agonist, and therefore can be usefully applied for preventing or treating dysfunction in gastrointestinal motility, one of the gastrointestinal diseases, such as gastroesophageal reflux disease (GERD), constipation, irritable bowel syndrome (IBS), dyspepsia, post-operative ileus, delayed gastric emptying, gastroparesis, intestinal pseudo-obstruction, drug-induced delayed transit, or diabetic gastric atony.
• Blocking Estrogen Signaling After the Hormone: Pyrimidine-Core Inhibitors of Estrogen Receptor-Coactivator Binding
  作者：Alexander A. Parent、Jillian R. Gunther、John A. Katzenellenbogen

  DOI：10.1021/jm800698b

  日期：2008.10.23

  As an alternative approach to blocking estrogen action, we have developed small molecules that directly disrupt the key estrogen receptor (ER)/coactivator interaction necessary for gene activation. The more direct, protein-protein nature of this disruption might be effective even in hormone-refractory breast cancer. We have synthesized a pyrimidine-core library of moderate size, members of which act as a-helix mimics to block the ER alpha/coactivator interaction. Structure-activity relationships have been explored with various C-, N-, O-, and S-substituents on the pyrimidine core. Time-resolved fluorescence resonance energy transfer and cell-based reporter gene assays show that the most active members inhibit the ER alpha/steroid receptor coactivator interaction with Ki's in the low micromolar range. Through these studies, we have obtained a refined pharmacophore model for activity in this pyrimidine series. Furthermore, the favorable activities of several of these compounds support the feasibility that this coactivator binding inhibition mechanism for blocking estrogen action might provide a potential alternative approach to endocrine therapy.