膦酸,[[2-(1,3-二氢-1,3-二羰基-2H-异吲哚-2-基)苯基]甲基]-,二乙基酯 | 140150-99-8

• 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
• 中文名称: 膦酸,[[2-(1,3-二氢-1,3-二羰基-2H-异吲哚-2-基)苯基]甲基]-,二乙基酯
• 英文名称: diethyl <<2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)phenyl>methyl>phosphonate
• 英文别名: 2-[2-(Diethoxyphosphorylmethyl)phenyl]isoindole-1,3-dione
• CAS: 140150-99-8
• 化学式: C₁₉H₂₀NO₅P
• 分子量: 373.345
• InChiKey: WKMJYHVQGRUZGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  膦酸,[[2-(1,3-二氢-1,3-二羰基-2H-异吲哚-2-基)苯基]甲基]-,二乙基酯 在 盐酸 、 sodium tetrahydroborate 作用下， 生成 diethyl <(2-aminophenyl)methyl>phosphonate
  参考文献：
  名称：

  Exploration of N-phosphonoalkyl-, N-phosphonoalkenyl-, and N-(phosphonoalkyl)phenyl-spaced .alpha.-amino acids as competitive N-methyl-D-aspartic acid antagonists

  摘要：

  A series of N-substituted alpha-amino acids containing terminal phosphonic acid groups has been synthesized as potential N-methyl-D-aspartate (NMDA) receptor antagonists. NMDA receptor affinity was determined by displacement of a known ligand ([H-3]CPP) from crude rat brain synaptic membranes; an antagonist action was demonstrated by the inhibition of glutamate-induced accumulation of [Ca-45(2+)] in cultured rat cortical neurons. Receptor affinity was significantly correlated with antagonist activity (Figure 1). Moderate affinity (IC50 = 1-2-mu-M) was retained for analogues (31 and 32, Table 1; and 59 and 66, Table II) with reduced flexibility in their phosphonate side chains and is consistent with entropy playing a role in determining receptor affinity. Modeling studies suggest a folded conformation that brings the distal phosphonic acid group into close proximity with the alpha-carboxylate is required for binding. Each of the active analogues possess entropy-limiting features (double bonds, phenyl rings) in their side chains that allows the superposition of their key NH2, alpha-COOH, and distal PO3H2 groups with those of known competitive antagonists. Affinity decreased for analogues with alpha-carbon substitution, presumably because the alpha-substituent inhibits the folding of these structures into a bioactive conformation and occupies receptor-excluded volume. A complete description of the NMDA antagonist pharmacophore model is provided in a companion paper. 1

  DOI：

  10.1021/jm00086a005
• 作为产物：
  描述：

  2-(2-甲基苯基)异吲哚-1,3-二酮 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 四氯化碳 、 氯仿 为溶剂， 反应 4.5h， 生成 膦酸,[[2-(1,3-二氢-1,3-二羰基-2H-异吲哚-2-基)苯基]甲基]-,二乙基酯
  参考文献：
  名称：

  Exploration of N-phosphonoalkyl-, N-phosphonoalkenyl-, and N-(phosphonoalkyl)phenyl-spaced .alpha.-amino acids as competitive N-methyl-D-aspartic acid antagonists

  摘要：

  A series of N-substituted alpha-amino acids containing terminal phosphonic acid groups has been synthesized as potential N-methyl-D-aspartate (NMDA) receptor antagonists. NMDA receptor affinity was determined by displacement of a known ligand ([H-3]CPP) from crude rat brain synaptic membranes; an antagonist action was demonstrated by the inhibition of glutamate-induced accumulation of [Ca-45(2+)] in cultured rat cortical neurons. Receptor affinity was significantly correlated with antagonist activity (Figure 1). Moderate affinity (IC50 = 1-2-mu-M) was retained for analogues (31 and 32, Table 1; and 59 and 66, Table II) with reduced flexibility in their phosphonate side chains and is consistent with entropy playing a role in determining receptor affinity. Modeling studies suggest a folded conformation that brings the distal phosphonic acid group into close proximity with the alpha-carboxylate is required for binding. Each of the active analogues possess entropy-limiting features (double bonds, phenyl rings) in their side chains that allows the superposition of their key NH2, alpha-COOH, and distal PO3H2 groups with those of known competitive antagonists. Affinity decreased for analogues with alpha-carbon substitution, presumably because the alpha-substituent inhibits the folding of these structures into a bioactive conformation and occupies receptor-excluded volume. A complete description of the NMDA antagonist pharmacophore model is provided in a companion paper. 1

  DOI：

  10.1021/jm00086a005

文献信息

• Exploration of N-phosphonoalkyl-, N-phosphonoalkenyl-, and N-(phosphonoalkyl)phenyl-spaced .alpha.-amino acids as competitive N-methyl-D-aspartic acid antagonists
  作者：Christopher F. Bigge、Graham Johnson、Daniel F. Ortwine、James T. Drummond、Daniel M. Retz、Laura J. Brahce、Linda L. Coughenour、Frank W. Marcoux、Albert W. Probert

  DOI：10.1021/jm00086a005

  日期：1992.4

  A series of N-substituted alpha-amino acids containing terminal phosphonic acid groups has been synthesized as potential N-methyl-D-aspartate (NMDA) receptor antagonists. NMDA receptor affinity was determined by displacement of a known ligand ([H-3]CPP) from crude rat brain synaptic membranes; an antagonist action was demonstrated by the inhibition of glutamate-induced accumulation of [Ca-45(2+)] in cultured rat cortical neurons. Receptor affinity was significantly correlated with antagonist activity (Figure 1). Moderate affinity (IC50 = 1-2-mu-M) was retained for analogues (31 and 32, Table 1; and 59 and 66, Table II) with reduced flexibility in their phosphonate side chains and is consistent with entropy playing a role in determining receptor affinity. Modeling studies suggest a folded conformation that brings the distal phosphonic acid group into close proximity with the alpha-carboxylate is required for binding. Each of the active analogues possess entropy-limiting features (double bonds, phenyl rings) in their side chains that allows the superposition of their key NH2, alpha-COOH, and distal PO3H2 groups with those of known competitive antagonists. Affinity decreased for analogues with alpha-carbon substitution, presumably because the alpha-substituent inhibits the folding of these structures into a bioactive conformation and occupies receptor-excluded volume. A complete description of the NMDA antagonist pharmacophore model is provided in a companion paper. 1