dimethyl 3,3′-(4-methoxyphenylazanediyl)dipropanoate | 56525-67-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: dimethyl 3,3′-(4-methoxyphenylazanediyl)dipropanoate
• 英文别名: p-Methoxy-phenylimino-β,β'-dipropionsaeure-dimethylester；methyl 3-[(2-methoxycarbonylethyl)-4-methoxyphenylamino]propanoate；methyl 3-(4-methoxy-N-(3-methoxy-3-oxopropyl)anilino)propanoate
• CAS: 56525-67-8
• 化学式: C₁₅H₂₁NO₅
• 分子量: 295.335
• InChiKey: HADJMSUVAXDZNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl 3,3′-(4-methoxyphenylazanediyl)dipropanoate 在 一水合肼 作用下， 以 异丙醇 为溶剂， 反应 48.0h， 以95%的产率得到3,3′-(4-methoxyphenylazanediyl)dipropanehydrazide
  参考文献：
  名称：

  Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of O6-Methylguanine-DNA-methyltransferase, DNA Mismatch Repair, and p53

  摘要：

  The antitumor prodrug temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (E.C. 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilinoethyl)-substituted imidazotetrazines are reported that have activity independent of MGMT, MMR, and p53. This is achieved through a switch of mechanism so that bioactivity derives from imidazotetrazine-generated arylaziridinium ions that principally modify guanine-N7 sites on DNA. Mono- and bifunctional analogues are reported, and a quantitative structure-activity relationship (QSAR) study identified the p-tolyl-substituted bifunctional congener as optimized for potency, MGMT-independence, and MMR-independence. NCI60 data show the tumor cell response is distinct from other imidazotetrazines and DNA-guanine-N7 active agents such as nitrogen mustards and cisplatin. The new imidazotetrazine compounds are promising agents for further development, and their improved in vitro activity validates the principles on which they were designed.

  DOI：

  10.1021/jm401121k
• 作为产物：
  描述：

  甲氧苯胺 、 丙烯酸甲酯（MA） 在 氯化锆(IV) 作用下， 反应 1.0h， 以75%的产率得到dimethyl 3,3′-(4-methoxyphenylazanediyl)dipropanoate
  参考文献：
  名称：

  An Efficient ZrCl4 Catalyzed Aza-Michael Addition Reaction: Synthesis of C-Linked Carbo β3-Amino Acids

  摘要：

  一种温和的aza-Michael反应方案已开发出来，使用ZrCl4作为催化剂，针对α, β-不饱和酯和腈类化合物。发现芳香胺能够轻松地得到产物。这种由ZrCl4催化的方法与酸敏感的碳水化合物酯相兼容，并提供了一种高效制备C-连接型碳水β3-氨基酸（β3-Caa）的途径。

  DOI：

  10.2174/157017809787582834

文献信息

• An Efficient ZrCl4 Catalyzed Aza-Michael Addition Reaction: Synthesis of C-Linked Carbo β3-Amino Acids
  作者：Krishna Damera、Katta Reddy、Gangavaram Sharma

  DOI：10.2174/157017809787582834

  日期：2009.3.1

  A mild aza-Michael protocol has been developed using ZrCl4 as catalyst on α, β-unsaturated esters and nitriles. The aromatic amines were found to give the products with ease. The ZrCl4 mediated route was compatible with acid sensitive carbohydrate esters and provided an efficient method to prepare C-linked carbo β3-amino acids (β3-Caa).

  一种温和的aza-Michael反应方案已开发出来，使用ZrCl4作为催化剂，针对α, β-不饱和酯和腈类化合物。发现芳香胺能够轻松地得到产物。这种由ZrCl4催化的方法与酸敏感的碳水化合物酯相兼容，并提供了一种高效制备C-连接型碳水β3-氨基酸（β3-Caa）的途径。
• Solvent-Promoted and -Controlled Aza-Michael Reaction with Aromatic Amines
  作者：Kavita De、Julien Legros、Benoit Crousse、Danièle Bonnet-Delpon

  DOI：10.1021/jo9012699

  日期：2009.8.21

  1,4-Addition of anilines onto Michael acceptors proceeds easily in specific polar protic solvent, without any promoting agent. According to the solvent and to the electrophile, the selectivity of the reaction can be finely tuned. With methyl acrylate as electrophile, only monoaddition takes place in water, while the diadduct is yielded in hexafluoroisopropyl alcohol (HFIP). The use of methyl vinyl ketone as a partner affords the monoadduct in water, the diadduct in trifluoroethanol (TFE), and the quinoline in HFIP.
• Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of <i>O</i>6-Methylguanine-DNA-methyltransferase, DNA Mismatch Repair, and p53
  作者：Dimitrios Pletsas、Elrashied A. E. Garelnabi、Li Li、Roger M. Phillips、Richard T. Wheelhouse

  DOI：10.1021/jm401121k

  日期：2013.9.12

  The antitumor prodrug temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (E.C. 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53. Novel 3-(2-anilinoethyl)-substituted imidazotetrazines are reported that have activity independent of MGMT, MMR, and p53. This is achieved through a switch of mechanism so that bioactivity derives from imidazotetrazine-generated arylaziridinium ions that principally modify guanine-N7 sites on DNA. Mono- and bifunctional analogues are reported, and a quantitative structure-activity relationship (QSAR) study identified the p-tolyl-substituted bifunctional congener as optimized for potency, MGMT-independence, and MMR-independence. NCI60 data show the tumor cell response is distinct from other imidazotetrazines and DNA-guanine-N7 active agents such as nitrogen mustards and cisplatin. The new imidazotetrazine compounds are promising agents for further development, and their improved in vitro activity validates the principles on which they were designed.