dimethyl N-(4-amino-3-methoxyphenyl)phosphoramidate | 86187-37-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: dimethyl N-(4-amino-3-methoxyphenyl)phosphoramidate
• 英文别名: 4-N-dimethoxyphosphoryl-2-methoxybenzene-1,4-diamine
• CAS: 86187-37-3
• 化学式: C₉H₁₅N₂O₄P
• 分子量: 246.203
• InChiKey: QGDGHCUSOLCGPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  82.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-methyl-9-chloroacridine 、 dimethyl N-(4-amino-3-methoxyphenyl)phosphoramidate 以 甲醇 、 乙酸乙酯 为溶剂， 生成 benzyl N-(2-methoxy-4-nitro-phenyl)carbamate
  参考文献：
  名称：

  Certain acridinyl-phosphoramidate compounds

  摘要：

  本发明的新类化合物由通式（I）表示：##STR1## 其中R1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，以及其酸加成盐，在体内抗肿瘤试验中表现出意外的高效力和活性。这些化合物还具有抑菌作用，并在培养基中对小鼠、仓鼠和人类肿瘤细胞系表现出毒性。

  公开号：

  US04479000A1
• 作为产物：
  描述：

  benzyl N-(4-amino-2-methoxy-phenyl)carbamate 在 吡啶 、 氢气 作用下， 生成 dimethyl N-(4-amino-3-methoxyphenyl)phosphoramidate
  参考文献：
  名称：

  Potential antitumor agents. 37. Organophosphorus derivatives of 9-anilinoacridine

  摘要：

  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).

  DOI：

  10.1021/jm00352a027

文献信息

• Potential antitumor agents. 52. Carbamate analogs of amsacrine with in vivo activity against multidrug-resistant P388 leukemia
  作者：Gordon W. Rewcastle、Bruce C. Baguley、Graham J. Atwell、William A. Denny

  DOI：10.1021/jm00392a009

  日期：1987.9

  provided increased activity against the multidrug-resistant P388/ADR leukemia subline in vivo. Since activity against such resistant tumors is of great clinical significance, a series of acridine-substituted carbamate derivatives were evaluated against both wild-type and ADR/resistant P388 leukemia and the Lewis lung solid tumor in vivo. Structure-activity relationships for all three tumor lines were similar

  对一系列与抗白血病药物氨苯磺酸有关的苯胺取代的9-苯胺基cr啶的研究表明，1'-氨基甲酸酯基团在体内对多药耐药的P388 / ADR白血病亚系提供增强的活性。由于针对这种抗药性肿瘤的活性具有重要的临床意义，因此在体内针对野生型和ADR /抗药性P388白血病以及Lewis肺实体瘤评估了一系列of啶取代的氨基甲酸酯衍生物。所有三个肿瘤细胞系的结构活性关系相似，其中3-卤代-5-甲基和3-卤代5-甲氧基化合物被证明是活性最高的。这种取代模式还提供了最高的DNA结合。此类化合物（尤其是3-氯-5-甲基和3-氯-5-甲氧基）对野生型P388和Lewis肺具有体内活性，其活性与先前开发的最佳氨水analogue类似物相当（治愈率超过50％） ，以及P388 / ADR活动。这项工作从根本上完成了amsacrine系列抗肿瘤药的开发。
• 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 O ，R2 代表 H、O 、CH3、卤素、NO2 NH2、NHCO 或 NHCOO ，R3 和 R4 分别代表 H、 、O 或 CONH ，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. 42. Structure-activity relationships for acridine-substituted dimethyl phosphoramidate derivatives of 9-anilinoacridine
  作者：Gordon W. Rewcastle、Graham J. Atwell、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm00374a020

  日期：1984.8

  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.
• 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