[(2-Amino-3,4-dioxo-cyclobut-1-enylamino)-methyl]-phosphonic acid diethyl ester | 1026003-91-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: [(2-Amino-3,4-dioxo-cyclobut-1-enylamino)-methyl]-phosphonic acid diethyl ester
• 英文别名: 3-Amino-4-(diethoxyphosphorylmethylamino)cyclobut-3-ene-1,2-dione
• CAS: 1026003-91-7
• 化学式: C₉H₁₅N₂O₅P
• 分子量: 262.202
• InChiKey: QHNMLAXBKULCGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [(2-Amino-3,4-dioxo-cyclobut-1-enylamino)-methyl]-phosphonic acid diethyl ester 在 三甲基溴硅烷 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 [[(2-amino-3,4-dioxo-1-cyclobutenyl)amino]methyl]phosphonic acid
  参考文献：
  名称：

  Bioisosteric replacement of the .alpha.-amino carboxylic acid functionality in 2-amino-5-phosphonopentanoic acid yields unique 3,4-diamino-3-cyclobutene-1,2-dione containing NMDA antagonists

  摘要：

  In this report, a novel bioisostere of the alpha-amino acid 3,4-diamino-3-cyclobutene-1,2-dione, has been incorporated into a series of compounds which are NMDA antagonists. These compounds, which are achiral and easily prepared, demonstrated good affinity at the NMDA receptor by their ability to displace [H-3]CPP binding in vitro. In particular, the phosphonic acid 24 provided protection against NMDA-induced lethality in mice equivalent to 2-amino-7-phosphonoheptanoic acid (5). This was considered an encouraging result in lieu of the fact that 24, like 5, lacks the conformational rigidity of the more potent NMDA antagonists. In addition, analogs that incorporate the 1,2,4-oxadiazolidine-3,5-dione heterocycle of quisqualic acid and the unsaturation of kainic acid were prepared to explore selectivity at the non-NMDA receptor subtypes.

  DOI：

  10.1021/jm00103a010
• 作为产物：
  描述：

  3-(Diethoxyphosphorylmethylamino)-4-ethoxycyclobut-3-ene-1,2-dione 在 氨 作用下， 生成 [(2-Amino-3,4-dioxo-cyclobut-1-enylamino)-methyl]-phosphonic acid diethyl ester
  参考文献：
  名称：

  Bioisosteric replacement of the .alpha.-amino carboxylic acid functionality in 2-amino-5-phosphonopentanoic acid yields unique 3,4-diamino-3-cyclobutene-1,2-dione containing NMDA antagonists

  摘要：

  In this report, a novel bioisostere of the alpha-amino acid 3,4-diamino-3-cyclobutene-1,2-dione, has been incorporated into a series of compounds which are NMDA antagonists. These compounds, which are achiral and easily prepared, demonstrated good affinity at the NMDA receptor by their ability to displace [H-3]CPP binding in vitro. In particular, the phosphonic acid 24 provided protection against NMDA-induced lethality in mice equivalent to 2-amino-7-phosphonoheptanoic acid (5). This was considered an encouraging result in lieu of the fact that 24, like 5, lacks the conformational rigidity of the more potent NMDA antagonists. In addition, analogs that incorporate the 1,2,4-oxadiazolidine-3,5-dione heterocycle of quisqualic acid and the unsaturation of kainic acid were prepared to explore selectivity at the non-NMDA receptor subtypes.

  DOI：

  10.1021/jm00103a010

文献信息

• Bioisosteric replacement of the .alpha.-amino carboxylic acid functionality in 2-amino-5-phosphonopentanoic acid yields unique 3,4-diamino-3-cyclobutene-1,2-dione containing NMDA antagonists
  作者：William A. Kinney、Nancy E. Lee、Deanna T. Garrison、Edward J. Podlesny、Joanne T. Simmonds、Donna Bramlett、Ronald R. Notvest、Dianne M. Kowal、Rene P. Tasse

  DOI：10.1021/jm00103a010

  日期：1992.12

  In this report, a novel bioisostere of the alpha-amino acid 3,4-diamino-3-cyclobutene-1,2-dione, has been incorporated into a series of compounds which are NMDA antagonists. These compounds, which are achiral and easily prepared, demonstrated good affinity at the NMDA receptor by their ability to displace [H-3]CPP binding in vitro. In particular, the phosphonic acid 24 provided protection against NMDA-induced lethality in mice equivalent to 2-amino-7-phosphonoheptanoic acid (5). This was considered an encouraging result in lieu of the fact that 24, like 5, lacks the conformational rigidity of the more potent NMDA antagonists. In addition, analogs that incorporate the 1,2,4-oxadiazolidine-3,5-dione heterocycle of quisqualic acid and the unsaturation of kainic acid were prepared to explore selectivity at the non-NMDA receptor subtypes.