2,6-bis[4-(4-carboxyoxazol-2-yl)-oxazol-2-yl]pyridine | 1221966-01-3

• 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[4-(4-carboxyoxazol-2-yl)-oxazol-2-yl]pyridine
• 英文别名: 2-[2-[6-[4-(4-Carboxy-1,3-oxazol-2-yl)-1,3-oxazol-2-yl]pyridin-2-yl]-1,3-oxazol-4-yl]-1,3-oxazole-4-carboxylic acid
• CAS: 1221966-01-3
• 化学式: C₁₉H₉N₅O₈
• 分子量: 435.309
• InChiKey: BVEUXHMMYZKPGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  192
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  2,6-bis[4-(4-carboxyoxazol-2-yl)-oxazol-2-yl]pyridine 、 二乙烯三胺 在 copper(II) bis(trifluoromethanesulfonate) 、 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 3.0h， 以15%的产率得到3,7,21,25-Tetraoxa-11,14,17,31,32,33,34,35-octazahexacyclo[25.3.1.12,5.16,9.119,22.123,26]pentatriaconta-1(31),2(35),4,6(34),8,19,22(33),23,26(32),27,29-undecaene-10,18-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：

  2,6-bis[4-[(4-methoxycarbonyl)oxazol-2-yl]oxazol-2-yl]pyridine 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以100%的产率得到2,6-bis[4-(4-carboxyoxazol-2-yl)-oxazol-2-yl]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

• Macrocyclic Pyridyl Polyoxazoles: Structure-Activity Studies of the Aminoalkyl Side-Chain on G-Quadruplex Stabilization and Cytotoxic Activity
  作者：Gifty Blankson、Suzanne Rzuczek、Cody Bishop、Daniel Pilch、Angela Liu、Leroy Liu、Edmond LaVoie、Joseph Rice

  DOI：10.3390/molecules181011938

  日期：——

  macrocyclic lactams comprised of a pyridine, four oxazoles and a phenyl ring. A derivative having a 2-(dimethylamino)ethyl chain attached to the 5-position of the phenyl ring was recently identified as a selective G-quadruplex stabilizer with excellent cytotoxic activity, and good in vivo anticancer activity against a human breast cancer xenograft in mice. Here we detail the synthesis of eight new

  吡啶基聚恶唑是由一个吡啶、四个恶唑和一个苯环组成的 24 元大环内酰胺。一种在苯环的 5-位上连接有 2-(二甲氨基)乙基链的衍生物最近被鉴定为一种选择性 G-四链体稳定剂，具有优异的细胞毒活性，并且在小鼠体内对人乳腺癌异种移植物具有良好的体内抗癌活性. 在这里，我们详细介绍了八种新的二甲氨基取代的吡啶基聚恶唑的合成，其中大环的连接点以及胺和大环之间的距离是变化的。评估每种化合物的选择性 G-四链体稳定性和细胞毒活性。活性更高的类似物具有直接连接到苯环或通过两个亚甲基与苯环隔开的胺。在人类肿瘤细胞系、RPMI 8402 (IC50 0.06-0.50 μM) 和 KB3- 1 (IC50 0.03–0.07 μM)。这些是高度选择性的 G-quadruplex 稳定剂，应该证明对于评估与 G-quaqdruplex 配体相关的生物活性的体外和体内机制特别有用。
• 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
• [EN] THERAPEUTIC COMPOUNDS<br/>[FR] COMPOSÉS THÉRAPEUTIQUES
  申请人：UNIV RUTGERS

  公开号：WO2011057126A1

  公开（公告）日：2011-05-12

  The invention provides compounds of formula (I) wherein u, d, v, m, n, R1, W, X, Y, and Z have any values defined herein, as well as salts thereof. The compounds have activity as anti-proliferative agents.
• 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.