N-(2-Phosphonophenyl)glycine | 140151-32-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(2-Phosphonophenyl)glycine
• 英文别名: 2-(2-Phosphonoanilino)acetic acid
• CAS: 140151-32-2
• 化学式: C₈H₁₀NO₅P
• 分子量: 231.145
• InChiKey: ATLJNNOMYMKLSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-溴苯胺 在 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 36.0h， 生成 N-(2-Phosphonophenyl)glycine
  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

• Methods for treating cancer using GRM8 inhibitors
  申请人：Flagship Pioneering Innovations V, Inc.

  公开号：US10683352B1

  公开（公告）日：2020-06-16

  The present invention provides methods for treating cancer using mGluR8 inhibitors, such as mGluR8 inhibitory antibodies and small molecules. The invention also features compositions containing mGluR8 inhibitors, methods of diagnosing patients with mGluR8-associated cancer, and methods of predicting the response of cancer in a subject to treatment with mGluR8 inhibitors.

  本发明提供了使用mGluR8抑制剂（如mGluR8抑制抗体和小分子）治疗癌症的方法。本发明还包括含有 mGluR8 抑制剂的组合物、诊断 mGluR8 相关癌症患者的方法以及预测癌症对 mGluR8 抑制剂治疗的反应的方法。
• TREATMENT AND/OR PREVENTION OF PRESBYCUSIS BY MODULATION OF METABOTROPIC GLUTAMATE RECEPTOR 7
  申请人：HOUSE EAR INSTITUTE

  公开号：EP2150244A1

  公开（公告）日：2010-02-10
• Treatment and/or Prevention of Presbycusis by Modulation of Metabotropic Glutamate Receptor 7
  申请人：Friedman Richard

  公开号：US20100197800A1

  公开（公告）日：2010-08-05

  The invention relates to the treatment and/or prevention of age-related hearing loss (presbycusis) with a modulator of a metabotropic glutamate receptor 7 (mGluR7).
• US5179085A
  申请人：——

  公开号：US5179085A

  公开（公告）日：1993-01-12
• [EN] TREATMENT AND/OR PREVENTION OF PRESBYCUSIS BY MODULATION OF METABOTROPIC GLUTAMATE RECEPTOR 7<br/>[FR] TRAITEMENT ET/OU PRÉVENTION DE LA PRESBYACOUSIE PAR LA MODULATION DU RÉCEPTEUR MÉTABOTROPIQUE DU GLUTAMATE DE TYPE 7
  申请人：HOUSE EAR INST

  公开号：WO2008131439A1

  公开（公告）日：2008-10-30

  [EN] The invention relates to the treatment and/or prevention of age-related hearing loss (presbycusis) with a modulator of a metabotropic glutamate receptor 7 (mGluR7).
  [FR] L'invention concerne le traitement et/ou la prévention de la perte de l'ouïe liée à l'âge (presbyacousie) avec un modulateur du récepteur métabotropique du glutamate de type 7 (mGluR7).