Methyl 2-[2-hydroxy-1-[[6-[[2-hydroxy-1-(4-methoxycarbonyl-1,3-oxazol-2-yl)ethyl]carbamothioyl]pyridine-2-carbonyl]amino]ethyl]-1,3-oxazole-4-carboxylate | 1301599-15-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: Methyl 2-[2-hydroxy-1-[[6-[[2-hydroxy-1-(4-methoxycarbonyl-1,3-oxazol-2-yl)ethyl]carbamothioyl]pyridine-2-carbonyl]amino]ethyl]-1,3-oxazole-4-carboxylate
• 英文别名: methyl 2-[2-hydroxy-1-[[6-[[2-hydroxy-1-(4-methoxycarbonyl-1,3-oxazol-2-yl)ethyl]carbamothioyl]pyridine-2-carbonyl]amino]ethyl]-1,3-oxazole-4-carboxylate
• CAS: 1301599-15-4
• 化学式: C₂₁H₂₁N₅O₉S
• 分子量: 519.492
• InChiKey: VGIZNNNPOLMSLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  231
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  Methyl 2-[2-hydroxy-1-[[6-[[2-hydroxy-1-(4-methoxycarbonyl-1,3-oxazol-2-yl)ethyl]carbamothioyl]pyridine-2-carbonyl]amino]ethyl]-1,3-oxazole-4-carboxylate 在 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 Methyl 2-[2-[6-[4-(4-methoxycarbonyl-1,3-oxazol-2-yl)-4,5-dihydro-1,3-thiazol-2-yl]pyridin-2-yl]-4,5-dihydro-1,3-oxazol-4-yl]-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-[[[1-(4-(methoxycarbonyl)oxazol-2-yl)-2-(triisopropylsilyloxy)ethyl]amino]thiocarbonyl]-6-[[[1-(4-(methoxycarbonyl)oxazol-2-yl)-2-(triisopropylsilyloxy)ethyl]amino]carbonyl]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-carbonyl]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

文献信息

• US8796300B2
  申请人：——

  公开号：US8796300B2

  公开（公告）日：2014-08-05
• Macrocyclic Pyridyl Polyoxazoles: Selective RNA and DNA G-Quadruplex Ligands as Antitumor Agents
  作者：Suzanne G. Rzuczek、Daniel S. Pilch、Angela Liu、Leroy Liu、Edmond J. LaVoie、Joseph E. Rice

  DOI：10.1021/jm1000612

  日期：2010.5.13

  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.