tert-butyl N-benzyl-N-[2-(naphthalen-1-ylmethylamino)-6-[(E)-2-phenylethenyl]pyrimidin-4-yl]carbamate | 1186025-84-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: tert-butyl N-benzyl-N-[2-(naphthalen-1-ylmethylamino)-6-[(E)-2-phenylethenyl]pyrimidin-4-yl]carbamate
• CAS: 1186025-84-2
• 化学式: C₃₅H₃₄N₄O₂
• 分子量: 542.681
• InChiKey: DFUKKBCCGUWHFC-QURGRASLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.1
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  5

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	benzyl-(2-chloro-6-styryl-pyrimidin-4-yl)-carbamic acid tert-butyl ester	1067679-07-5	C24H24ClN3O2	421.926

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	benzyl-{2-[(naphthalen-1-ylmethyl)-amino]-6-phenethyl-pyrimidin-4-yl}-carbamic acid tert-butyl ester	1067679-13-3	C35H36N4O2	544.696
  ——	N4-benzyl-N2-naphthalen-1-ylmethyl-6-styryl-pyrimidine-2,4-diamine	1067679-17-7	C30H26N4	442.563

反应信息

• 作为反应物：
  描述：

  tert-butyl N-benzyl-N-[2-(naphthalen-1-ylmethylamino)-6-[(E)-2-phenylethenyl]pyrimidin-4-yl]carbamate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.0h， 以100%的产率得到benzyl-{2-[(naphthalen-1-ylmethyl)-amino]-6-phenethyl-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：

  benzyl-(2-chloro-6-styryl-pyrimidin-4-yl)-carbamic acid tert-butyl ester 、 1-萘甲基胺 以 二甲基亚砜 为溶剂， 反应 7.0h， 以66%的产率得到tert-butyl N-benzyl-N-[2-(naphthalen-1-ylmethylamino)-6-[(E)-2-phenylethenyl]pyrimidin-4-yl]carbamate
  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