dimethyl N-(4-aminophenyl)phosphoramidate | 82720-54-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: dimethyl N-(4-aminophenyl)phosphoramidate
• 英文别名: 4-N-dimethoxyphosphorylbenzene-1,4-diamine
• CAS: 82720-54-5
• 化学式: C₈H₁₃N₂O₃P
• 分子量: 216.177
• InChiKey: OCHAQEDPKNHDDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethyl N-(4-aminophenyl)phosphoramidate 在 palladium on activated charcoal 盐酸 、 ammonium hydroxide 、 氢气 作用下， 以 甲醇 为溶剂， 生成 dimethyl N-{4-[(3-amino-9-acridinyl)amino]phenyl}phosphoramidate
  参考文献：
  名称：

  Potential antitumor agents. 42. Structure-activity relationships for acridine-substituted dimethyl phosphoramidate derivatives of 9-anilinoacridine

  摘要：

  Replacement of the 1'-methanesulfonamide group of the 9-anilinoacridine class of antitumor agents with the 1'-(dimethyl phosphoramidate) group provides compounds that are generally more lipophilic and bind more tightly to DNA. On the average, the dimethyl phosphoramidates are twice as dose potent as the corresponding methanesulfonamide (AMSA) compounds against P388 leukemia in vivo, but also show about twice the acute toxicity and no resultant improvement in tumor cell selectivity (ILSmax values) is seen. A pairwise comparison of a range of acridine-substituted compounds shows that structure-activity relationships within each series are similar and dominated by the acridine substitution pattern.

  DOI：

  10.1021/jm00374a020
• 作为产物：
  描述：

  N-4-nitrophenyl-dimethyl phosphoramidic acid ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 以100%的产率得到dimethyl N-(4-aminophenyl)phosphoramidate
  参考文献：
  名称：

  Potential antitumor agents. 42. Structure-activity relationships for acridine-substituted dimethyl phosphoramidate derivatives of 9-anilinoacridine

  摘要：

  Replacement of the 1'-methanesulfonamide group of the 9-anilinoacridine class of antitumor agents with the 1'-(dimethyl phosphoramidate) group provides compounds that are generally more lipophilic and bind more tightly to DNA. On the average, the dimethyl phosphoramidates are twice as dose potent as the corresponding methanesulfonamide (AMSA) compounds against P388 leukemia in vivo, but also show about twice the acute toxicity and no resultant improvement in tumor cell selectivity (ILSmax values) is seen. A pairwise comparison of a range of acridine-substituted compounds shows that structure-activity relationships within each series are similar and dominated by the acridine substitution pattern.

  DOI：

  10.1021/jm00374a020

文献信息

• Compounds having antitumour activity
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0073155A2

  公开（公告）日：1983-03-02

  The novel class of compounds of the present invention represented by the general formula (I): in which R, represents H or OCH3, R2 represents H, OCH3, CH3, halogen, NO2 NH2, NHCOCH3 or NHCOOCH3, and R3 and R4 individually represent H, CH3, OCH3 or CONHCH3, and the acid addition salts thereof, have unexpectedly high potency and activity in in vivo antitumor tests. The compounds are also bacteriostatic, and show toxicity towards mouse, hamster and human tumour cell lines in culture.

  由通式（I）表示的本发明新型化合物：其中 R 代表 H 或 OCH3，R2 代表 H、OCH3、CH3、卤素、NO2 NH2、NHCOCH3 或 NHCOOCH3，R3 和 R4 分别代表 H、CH3、OCH3 或 CONHCH3，以及它们的酸加成盐，在体内抗肿瘤试验中具有出乎意料的高效力和活性。 这些化合物还具有抑菌作用，并对培养中的小鼠、仓鼠和人类肿瘤细胞系具有毒性。
• Potential antitumor agents. 37. Organophosphorus derivatives of 9-anilinoacridine
  作者：Gordon W. Rewcastle、Bruce C. Baguley、Bruce F. Cain

  DOI：10.1021/jm00352a027

  日期：1982.10

  A series of 9-anilinoacridine derivatives substituted in the anilino ring with a variety of phosphoramide and related substitutents has been prepared, and the antitumor activity has been evaluated both in vivo and in vitro against the L1210 or P-388 mouse leukemia systems. The DNA-binding properties were measured using the ethidium displacement method, and the structural requirements for strong binding were found to differ from those for antileukemic activity. For high biological activity a marked preference for oxygen-containing substituents on the phosphorus atom was noted, while for high DNA binding a requirement for nitrogen-containing or cyclized substituents was observed. The most active congeners, as assayed in both in vitro and in vivo systems, were comparable in activity to the clinically utilized anilinoacridine derivative N-[4'-(9-acridinylamino)-3'-methoxyphenyl]methanesulfonamide (m-AMSA, amsacrine).
• REWCASTLE, G. W.;BAGULEY, B. C.;CAIN, B. F., J. MED. CHEM., 1982, 25, N 10, 1231-1235
  作者：REWCASTLE, G. W.、BAGULEY, B. C.、CAIN, B. F.

  DOI：——

  日期：——
• US4479000A
  申请人：——

  公开号：US4479000A

  公开（公告）日：1984-10-23
• US4537729A
  申请人：——

  公开号：US4537729A

  公开（公告）日：1985-08-27