2,6-bis[[[1-(4-(methoxycarbonyl)oxazol-2-yl)-2-(triisopropylsilyloxy)ethyl]amino]thiocarbonyl]pyridine | 1221966-08-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2,6-bis[[[1-(4-(methoxycarbonyl)oxazol-2-yl)-2-(triisopropylsilyloxy)ethyl]amino]thiocarbonyl]pyridine
• 英文别名: Methyl 2-[1-[[6-[[1-(4-methoxycarbonyl-1,3-oxazol-2-yl)-2-tri(propan-2-yl)silyloxyethyl]carbamothioyl]pyridine-2-carbothioyl]amino]-2-tri(propan-2-yl)silyloxyethyl]-1,3-oxazole-4-carboxylate
• CAS: 1221966-08-0
• 化学式: C₃₉H₆₁N₅O₈S₂Si₂
• 分子量: 848.245
• InChiKey: BNVNDNSNOQQBMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.03
• 重原子数：
  56
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  224
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  2,6-bis[[[1-(4-(methoxycarbonyl)oxazol-2-yl)-2-(triisopropylsilyloxy)ethyl]amino]thiocarbonyl]pyridine 在 pyridine hydrofluoride 作用下， 以 四氢呋喃 、 吡啶 为溶剂， 生成 Methyl 2-[2-hydroxy-1-[[6-[[2-hydroxy-1-(4-methoxycarbonyl-1,3-oxazol-2-yl)ethyl]carbamothioyl]pyridine-2-carbothioyl]amino]ethyl]-1,3-oxazole-4-carboxylate
  参考文献：
  名称：

  Macrocyclic Pyridyl Polyoxazoles: Selective RNA and DNA G-Quadruplex Ligands as Antitumor Agents

  摘要：

  The synthesis of a series of 24-membered pyridine-containing polyoxazole macrocycles is described. Seventeen new macrocycles were evaluated for cytotoxic activity against RPMI 8402, KB-3, and KB-3 cell lines that overexpress the efflux transporters MDR1 (KBV-1) and BCRP (KBH5.0). Macrocycles in which the pyridyl-polyoxazole moiety is linked by a 1,3-bis(aminomethyl)phenyl group with a 5-(2-aminoethyl)- (18) or a 5-(2-dimethylaminoethyl)- substituent (19) displayed the greatest cytotoxic potency. These compounds exhibit exquisite selectivity for stabilizing G-quadruplex DNA with no stabilization of duplex DNA or RNA. Compound 19 stabilizes quadruplex mRNA that encodes the cell-cycle checkpoint protein kinase Aurora A to a greater extent than the quadruplex DNA of a human telomeric sequence. These data may suggest a role for G-quadruplex ligands interacting with mRNA being associated with the biological activity of macrocyclic polyoxazoles. Compound 19 has significant in vivo anticancer activity against a human breast cancer xenograft (MDA-MB-435) in athymic nude mice.

  DOI：

  10.1021/jm1000612
• 作为产物：
  描述：

  2,6-bis-[[[1-(4-(methoxycarbonyl)oxazol-2-yl)-2-(triisopropylsilyloxy)-ethyl]amino]carbonyl]pyridine 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以88%的产率得到2,6-bis[[[1-(4-(methoxycarbonyl)oxazol-2-yl)-2-(triisopropylsilyloxy)ethyl]amino]thiocarbonyl]pyridine
  参考文献：
  名称：

  Macrocyclic Pyridyl Polyoxazoles: Selective RNA and DNA G-Quadruplex Ligands as Antitumor Agents

  摘要：

  The synthesis of a series of 24-membered pyridine-containing polyoxazole macrocycles is described. Seventeen new macrocycles were evaluated for cytotoxic activity against RPMI 8402, KB-3, and KB-3 cell lines that overexpress the efflux transporters MDR1 (KBV-1) and BCRP (KBH5.0). Macrocycles in which the pyridyl-polyoxazole moiety is linked by a 1,3-bis(aminomethyl)phenyl group with a 5-(2-aminoethyl)- (18) or a 5-(2-dimethylaminoethyl)- substituent (19) displayed the greatest cytotoxic potency. These compounds exhibit exquisite selectivity for stabilizing G-quadruplex DNA with no stabilization of duplex DNA or RNA. Compound 19 stabilizes quadruplex mRNA that encodes the cell-cycle checkpoint protein kinase Aurora A to a greater extent than the quadruplex DNA of a human telomeric sequence. These data may suggest a role for G-quadruplex ligands interacting with mRNA being associated with the biological activity of macrocyclic polyoxazoles. Compound 19 has significant in vivo anticancer activity against a human breast cancer xenograft (MDA-MB-435) in athymic nude mice.

  DOI：

  10.1021/jm1000612