N-(2-苯氧基苯基)-3-硝基邻氨基苯甲酸 | 103942-78-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(2-苯氧基苯基)-3-硝基邻氨基苯甲酸
• 英文名称: N-(2-phenoxyphenyl)-3-nitroanthranilic acid
• 英文别名: 3-Nitro-2-(2-phenoxyanilino)benzoic acid
• CAS: 103942-78-5
• 化学式: C₁₉H₁₄N₂O₅
• 分子量: 350.331
• InChiKey: VTFVCPVVYVFANK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2-苯氧基苯基)-3-硝基邻氨基苯甲酸 在 sodium hydroxide 、 sodium tetrahydroborate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.5h， 生成 咪唑-1-基-(9-苯氧基-吩嗪-1-基)-甲酮
  参考文献：
  名称：

  Bis(phenazine-1-carboxamides):  Structure−Activity Relationships for a New Class of Dual Topoisomerase I/II-Directed Anticancer Drugs

  摘要：

  Ring-substituted bis(phenazine-1-carboxamides), linked by a -(CH2)(3)NMe(CH2)(3)- chain, were prepared from the corresponding substituted phenazine-1-carboxylic acids by reaction of the intermediate imidazolides with bis(3-aminopropyl)methylamine. The compounds were evaluated for growth inhibitory activity in a panel of tumor cell lines, including P388 leukemia, Lewis lung carcinoma, and wild-type (JL(C)) and mutant (JL(A) and JL(D)) forms of human Jurkat leukemia; The latter mutant lines are resistant to topoisomerase (topo) II targeted agents because of lower levels of the enzyme. Analogues with small, lipophilic substituents (e.g,, Me, Cl) at the 9-position were the most potent inhibitors, superior to the corresponding dimeric bis(acridine-4-carboxamides) (bis-DACA analogues). Several of the compounds were preferentially (up to 2-fold) more cytotoxic toward the mutant Jurkat lines than the wild-type. To test whether this selectivity was related to topoisomerase action, the most potent of the compounds (9-methyl) was evaluated in a cell-free system. It poisoned topo I at drug concentrations of 0.25 and 0.5 mu M and inhibited the catalytic activity of both topo I and topo II at concentrations of 1 and 5 mu M, respectively. Results from the NCI human tumor cell line panel showed the compounds had preferential activity toward colon tumor lines ton average 9.5-fold more active in the HT29 line than in the cell line, panel as a whole). Several analogues produced significant growth delays in the relatively refractory subcutaneous colon 38 tumor model in vivo. In particular, the 9-methyl compound was substantially more potent in this tumor model than the clinical dual topo I/II poison DACA (total dose 90 versus 400 mg/kg) with comparable activity. The bis(phenazine-1-carboxamides) are a new and interesting class of dual topo I/II-directed anticancer drugs.

  DOI：

  10.1021/jm990423f
• 作为产物：
  描述：

  2-溴-3-硝基苯甲酸 、 2-氨基二苯醚 在 copper(l) chloride N-乙基吗啉 作用下， 以 various solvent(s) 为溶剂， 反应 4.0h， 以91%的产率得到N-(2-苯氧基苯基)-3-硝基邻氨基苯甲酸
  参考文献：
  名称：

  Bis(phenazine-1-carboxamides):  Structure−Activity Relationships for a New Class of Dual Topoisomerase I/II-Directed Anticancer Drugs

  摘要：

  Ring-substituted bis(phenazine-1-carboxamides), linked by a -(CH2)(3)NMe(CH2)(3)- chain, were prepared from the corresponding substituted phenazine-1-carboxylic acids by reaction of the intermediate imidazolides with bis(3-aminopropyl)methylamine. The compounds were evaluated for growth inhibitory activity in a panel of tumor cell lines, including P388 leukemia, Lewis lung carcinoma, and wild-type (JL(C)) and mutant (JL(A) and JL(D)) forms of human Jurkat leukemia; The latter mutant lines are resistant to topoisomerase (topo) II targeted agents because of lower levels of the enzyme. Analogues with small, lipophilic substituents (e.g,, Me, Cl) at the 9-position were the most potent inhibitors, superior to the corresponding dimeric bis(acridine-4-carboxamides) (bis-DACA analogues). Several of the compounds were preferentially (up to 2-fold) more cytotoxic toward the mutant Jurkat lines than the wild-type. To test whether this selectivity was related to topoisomerase action, the most potent of the compounds (9-methyl) was evaluated in a cell-free system. It poisoned topo I at drug concentrations of 0.25 and 0.5 mu M and inhibited the catalytic activity of both topo I and topo II at concentrations of 1 and 5 mu M, respectively. Results from the NCI human tumor cell line panel showed the compounds had preferential activity toward colon tumor lines ton average 9.5-fold more active in the HT29 line than in the cell line, panel as a whole). Several analogues produced significant growth delays in the relatively refractory subcutaneous colon 38 tumor model in vivo. In particular, the 9-methyl compound was substantially more potent in this tumor model than the clinical dual topo I/II poison DACA (total dose 90 versus 400 mg/kg) with comparable activity. The bis(phenazine-1-carboxamides) are a new and interesting class of dual topo I/II-directed anticancer drugs.

  DOI：

  10.1021/jm990423f

文献信息

• Phenazinecarboxamide compounds
  申请人：DEVELOPMENT FINANCE CORPORATION OF NEW ZEALAND

  公开号：EP0172744A2

  公开（公告）日：1986-02-26

  The novel class of phenazine derivatives of the present invention represented by the general formula where R, represents H or up to three substituents, at positions selected from 2 to 4 and 6 to 9, wherein any two or all of the substituents may be the same or different and the substituents are selected from lower alkyl radicals; lower alkyl radicals substituted by one or more of the same or different substituents selected from hydroxy, amino and ether functions; OH, SH; OCH2Ph; OPh; N02; halogen; CF3; amino; NHSO2R2, NHCOR2, NHCOOR2, OR2 and SR2 (where R2 represents a lower alkyl radical which is unsubstituted or substituted by one or more of the same or different substituents selected from hydroxy, amino and ether functions); and CONH(CH2)n'Y (where n' and Y' are as defined below), there being a maximum of one CONH(CH2)n'Y' group; or any two of R, at adjacent positions represent -CH=CH-CH=CH- as part of an extra benzene ring or -O-CH2-O- (methylenedioxy) and the third of R, has any one of the meanings given above with the exception of an OH at position 2; Y and Y', which may be the same or different, each represents C(NH)NH2, NHC(NH)NH2 or NR3R4, where each of R3 and R4, which may be the same or different, represents H or a lower alkyl radical unsubstituted or substituted by one or more of the same or different substituents selected from hydroxy, amino and ether functions, or R3 and R4, together with the nitrogen atom to which they are attached, form a heterocyclic ring; and n and n', which may be the same or different, each represents an integer from 2 to 6; and the acid addition salts, 5- and 10- mono-N-oxides and 5,10-di-N-oxides thereof, possess antibacterial and antitumour properties.

  本发明的一类新型吩嗪衍生物由通式表示 其中 R 代表 H 或最多三个取代基，位于选自 2 至 4 和 6 至 9 的位置，其中任意两个或所有取代基可以相同或不同，取代基选自 低级烷基 被一个或多个相同或不同的取代基取代的低级烷基，取代基可选自羟基、氨基和醚官能团； 羟基 SH； OCH2Ph； OPh； N02; 卤素；CF3；氨基； NHSO2R2、NHCOR2、NHCOOR2、OR2 和 SR2（其中 R2 代表未被取代或被一个或多个选自羟基、氨基和醚官能团的相同或不同取代基取代的低级烷基）；以及 CONH(CH2)n'Y（其中 n'和 Y'定义如下），最多一个 CONH(CH2)n'Y'基团；或相邻位置的任意两个 R 代表-CH=CH-CH=CH-（作为额外苯环的一部分）或-O-CH2-O-（亚甲基二氧基），第三个 R 具有上述任何一种含义，但位置 2 上的 OH 除外； Y 和 Y'（可以相同或不同）各自代表 C(NH)NH2、NHC(NH)NH2 或 NR3R4，其中 R3 和 R4（可以相同或不同）各自代表 H 或未取代的低级烷基或被选自羟基、氨基和醚官能团的一个或多个相同或不同取代基取代的低级烷基，或 R3 和 R4 与它们所连接的氮原子一起形成杂环；以及 n 和 n'（可以相同或不同）分别代表 2 至 6 的整数；酸加成盐、5-和 10-单-N-氧化物及其 5,10-二-N-氧化物具有抗菌和抗肿瘤特性。
• Bis(phenazine-1-carboxamides):  Structure−Activity Relationships for a New Class of Dual Topoisomerase I/II-Directed Anticancer Drugs
  作者：Julie A. Spicer、Swarna A. Gamage、Gordon W. Rewcastle、Graeme J. Finlay、David J. A. Bridewell、Bruce C. Baguley、William A. Denny

  DOI：10.1021/jm990423f

  日期：2000.4.6

  Ring-substituted bis(phenazine-1-carboxamides), linked by a -(CH2)(3)NMe(CH2)(3)- chain, were prepared from the corresponding substituted phenazine-1-carboxylic acids by reaction of the intermediate imidazolides with bis(3-aminopropyl)methylamine. The compounds were evaluated for growth inhibitory activity in a panel of tumor cell lines, including P388 leukemia, Lewis lung carcinoma, and wild-type (JL(C)) and mutant (JL(A) and JL(D)) forms of human Jurkat leukemia; The latter mutant lines are resistant to topoisomerase (topo) II targeted agents because of lower levels of the enzyme. Analogues with small, lipophilic substituents (e.g,, Me, Cl) at the 9-position were the most potent inhibitors, superior to the corresponding dimeric bis(acridine-4-carboxamides) (bis-DACA analogues). Several of the compounds were preferentially (up to 2-fold) more cytotoxic toward the mutant Jurkat lines than the wild-type. To test whether this selectivity was related to topoisomerase action, the most potent of the compounds (9-methyl) was evaluated in a cell-free system. It poisoned topo I at drug concentrations of 0.25 and 0.5 mu M and inhibited the catalytic activity of both topo I and topo II at concentrations of 1 and 5 mu M, respectively. Results from the NCI human tumor cell line panel showed the compounds had preferential activity toward colon tumor lines ton average 9.5-fold more active in the HT29 line than in the cell line, panel as a whole). Several analogues produced significant growth delays in the relatively refractory subcutaneous colon 38 tumor model in vivo. In particular, the 9-methyl compound was substantially more potent in this tumor model than the clinical dual topo I/II poison DACA (total dose 90 versus 400 mg/kg) with comparable activity. The bis(phenazine-1-carboxamides) are a new and interesting class of dual topo I/II-directed anticancer drugs.