isobutyl-(2-isobutylsulfanyl-6-(3-methyl-butyl)-pyrimidin-4-yl)-carbamic acid tert-butyl ester | 1067678-96-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: isobutyl-(2-isobutylsulfanyl-6-(3-methyl-butyl)-pyrimidin-4-yl)-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[6-(3-methylbutyl)-2-(2-methylpropylsulfanyl)pyrimidin-4-yl]-N-(2-methylpropyl)carbamate
• CAS: 1067678-96-9
• 化学式: C₂₂H₃₉N₃O₂S
• 分子量: 409.637
• InChiKey: VJMVJXUZAUMFRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  80.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  isobutyl-(2-isobutylsulfanyl-6-(3-methyl-butyl)-pyrimidin-4-yl)-carbamic acid tert-butyl ester 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 反应 16.0h， 以40%的产率得到isobutyl-(6-(3-methyl-butyl)-2-(2-methyl-propane-1-sulfonyl)-pyrimidin-4-yl)-carbamic acid tert-butyl ester
  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：

  异丁硫醇 、 (2-chloro-6-(3-methyl-butyl)-pyrimidin-4-yl)-isobutyl-carbamic acid tert-butyl ester 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 16.25h， 以78%的产率得到isobutyl-(2-isobutylsulfanyl-6-(3-methyl-butyl)-pyrimidin-4-yl)-carbamic acid tert-butyl ester
  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

文献信息

• 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.