2-[2-[6-[4-[4-[[3-[[(2-Methylpropan-2-yl)oxycarbonylamino]methyl]phenyl]methylcarbamoyl]-1,3-oxazol-2-yl]-1,3-thiazol-2-yl]pyridin-2-yl]-1,3-thiazol-4-yl]-1,3-oxazole-4-carboxylic acid | 1301599-28-9

• 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-[2-[6-[4-[4-[[3-[[(2-Methylpropan-2-yl)oxycarbonylamino]methyl]phenyl]methylcarbamoyl]-1,3-oxazol-2-yl]-1,3-thiazol-2-yl]pyridin-2-yl]-1,3-thiazol-4-yl]-1,3-oxazole-4-carboxylic acid
• CAS: 1301599-28-9
• 化学式: C₃₂H₂₇N₇O₇S₂
• 分子量: 685.741
• InChiKey: PIBPYGHPVCMUJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  48
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  252
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  2-[2-[6-[4-[4-[[3-[[(2-Methylpropan-2-yl)oxycarbonylamino]methyl]phenyl]methylcarbamoyl]-1,3-oxazol-2-yl]-1,3-thiazol-2-yl]pyridin-2-yl]-1,3-thiazol-4-yl]-1,3-oxazole-4-carboxylic acid 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 2.0h， 以25 mg的产率得到
  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-[2-[6-[4-(4-Carboxy-1,3-oxazol-2-yl)-1,3-thiazol-2-yl]pyridin-2-yl]-1,3-thiazol-4-yl]-1,3-oxazole-4-carboxylic acid 、 N-[3-(氨基甲基)苄基]氨基甲酸叔丁酯 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 2,6-二甲基吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-[2-[6-[4-[4-[[3-[[(2-Methylpropan-2-yl)oxycarbonylamino]methyl]phenyl]methylcarbamoyl]-1,3-oxazol-2-yl]-1,3-thiazol-2-yl]pyridin-2-yl]-1,3-thiazol-4-yl]-1,3-oxazole-4-carboxylic acid
  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

• THERAPEUTIC COMPOUNDS
  申请人：LaVoie Edmond J.

  公开号：US20120238595A1

  公开（公告）日：2012-09-20

  The invention provides compounds of formula (I) wherein u, d, v, m, n, R 1 , W, X, Y, and Z have any values defined herein, as well as salts thereof. The compounds have activity as anti-proliferative agents.
• US8796300B2
  申请人：——

  公开号：US8796300B2

  公开（公告）日：2014-08-05