2,6-bis[4-(4-carboxyoxazol-2-yl)oxazol-2-yl]-4-[(3-phthalimidopropyl)oxy]pyridine | 1221966-33-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2,6-bis[4-(4-carboxyoxazol-2-yl)oxazol-2-yl]-4-[(3-phthalimidopropyl)oxy]pyridine
• 英文别名: 2-[2-[6-[4-(4-Carboxy-1,3-oxazol-2-yl)-1,3-oxazol-2-yl]-4-[3-(1,3-dioxoisoindol-2-yl)propoxy]pyridin-2-yl]-1,3-oxazol-4-yl]-1,3-oxazole-4-carboxylic acid
• CAS: 1221966-33-1
• 化学式: C₃₀H₁₈N₆O₁₁
• 分子量: 638.507
• InChiKey: IIVHVOPLXWTQJC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  47
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  238
• 氢给体数：
  2
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  间苯二甲胺 、 2,6-bis[4-(4-carboxyoxazol-2-yl)oxazol-2-yl]-4-[(3-phthalimidopropyl)oxy]pyridine 在 2,6-二甲基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以35%的产率得到31-[3-(1,3-Dioxoisoindol-2-yl)propoxy]-3,7,23,27-tetraoxa-11,19,33,34,35,37,38-heptazaheptacyclo[27.3.1.12,5.16,9.113,17.121,24.125,28]octatriaconta-1(32),2(38),4,6(37),8,13,15,17(36),21,24(35),25,28(34),29(33),30-tetradecaene-10,20-dione
  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：

  Methyl 2-[2-[4-[3-(1,3-dioxoisoindol-2-yl)propoxy]-6-[4-(4-methoxycarbonyl-1,3-oxazol-2-yl)-1,3-oxazol-2-yl]pyridin-2-yl]-1,3-oxazol-4-yl]-1,3-oxazole-4-carboxylate 在 lithium chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以100%的产率得到2,6-bis[4-(4-carboxyoxazol-2-yl)oxazol-2-yl]-4-[(3-phthalimidopropyl)oxy]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

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.