2-[(2,5-dimethylphenyl)amino]-3-nitrobenzoic acid | 116702-56-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[(2,5-dimethylphenyl)amino]-3-nitrobenzoic acid
• 英文别名: 2-(2,5-Dimethyl phenylamino)-3-nitro benzoic acid；2-(2,5-dimethylanilino)-3-nitrobenzoic acid
• CAS: 116702-56-8
• 化学式: C₁₅H₁₄N₂O₄
• 分子量: 286.287
• InChiKey: MTAHHTJUJQNXIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  95.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(2,5-dimethylphenyl)amino]-3-nitrobenzoic acid 在 sodium ethanolate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 (6,9-二甲基-吩嗪-1-基)-咪唑-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 、 2,5-二甲基苯胺 以gave 2-(2,5-dimethyl phenylamino)-3-nitro benzoic acid (65%)的产率得到2-[(2,5-dimethylphenyl)amino]-3-nitrobenzoic acid
  参考文献：
  名称：

  Bis(acridinecarboxamide) and bis(phenazinecarboxamide) as antitumor

  摘要：

  化合物为公式（I）的双（吖啶羧酰胺）或双（菲嗪羧酰胺）衍生物：其中每个X在给定的分子中可能相同或不同，为--CH.dbd.或--N.dbd.；每个R.sub.1到R.sub.4在给定的分子中可能相同或不同，为H、C.sub.1-C.sub.4烷基、OH、SH、NH.sub.2、C.sub.1-C.sub.4烷氧基、芳氧基、NHR、N（R）.sub.2、SR、SO.sub.2R，其中R为C.sub.1-C.sub.4烷基、CF.sub.3、NO.sub.2或卤素，或R.sub.1和R.sub.2共同形成一个亚甲二氧基基团；每个R.sub.5和R.sub.6，可能相同或不同，为H或C.sub.1-C.sub.4烷基；Z为（CH.sub.2）.sub.n、（CH.sub.2）.sub.n O（CH.sub.2）.sub.n、（CH.sub.2）.sub.n N（R.sub.7）（CH.sub.2）.sub.n、（CH.sub.2）.sub.n N（R.sub.7）（CH.sub.2）.sub.m N（R.sub.7）（CH.sub.2）.sub.n或（CH.sub.2）.sub.n N（CH.sub.2CH.sub.2）.sub.2N（CH.sub.2）.sub.n，其中R.sub.7为H或C.sub.1-C.sub.4烷基，n和m可能相同或不同，均为1至4的整数；或其药学上可接受的酸加盐或N-氧化物；具有抗肿瘤和抗菌活性。

  公开号：

  US06114332A1

文献信息

• Bis(acridinecarboxamide) and bis(phenazinecarboxamide) as antitumor
  申请人：Xenova Limited

  公开号：US06114332A1

  公开（公告）日：2000-09-05

  A compound which is a bis(acridinecarboxamide) or bis(phenazinecarboxamide) derivative of formula (I): ##STR1## wherein each X, which may be the same or different in a given molecule, is --CH.dbd. or --N.dbd. each of R.sub.1 to R.sub.4 which may be the same or different, H, C.sub.1 -C.sub.4 alkyl, OH, SH, NH.sub.2, C.sub.1 -C.sub.4 alkoxy, aryloxy, NHR, N(R).sub.2, SR, SO.sub.2 R wherein R is C.sub.1 -C.sub.4 alkyl, CF.sub.3, NO.sub.2 or halogen, or R.sub.1 and R.sub.2 together form a methylenedioxy group; each of R.sub.5 and R.sub.6, which may be the same or different, is H or C.sub.1 -C.sub.4 alkyl; Z is (CH.sub.2).sub.n, (CH.sub.2).sub.n O(CH.sub.2).sub.n, (CH.sub.2).sub.n N(R.sub.7)(CH.sub.2).sub.n, (CH.sub.2).sub.n N(R.sub.7)(CH.sub.2).sub.m N(R.sub.7)(CH.sub.2).sub.n or (CH.sub.2).sub.n N(CH.sub.2 CH.sub.2).sub.2 N(CH.sub.2).sub.n wherein R.sub.7 is H or C.sub.1 -C.sub.4 alkyl and n and m, which may be the same or different, are each an integer of 1 to 4; or a pharmaceutically acceptable acid addition salt or N-oxide thereof; has activity as an antitumor and antibacterial agent.

  化合物为公式（I）的双（吖啶羧酰胺）或双（菲嗪羧酰胺）衍生物：其中每个X在给定的分子中可能相同或不同，为--CH.dbd.或--N.dbd.；每个R.sub.1到R.sub.4在给定的分子中可能相同或不同，为H、C.sub.1-C.sub.4烷基、OH、SH、NH.sub.2、C.sub.1-C.sub.4烷氧基、芳氧基、NHR、N（R）.sub.2、SR、SO.sub.2R，其中R为C.sub.1-C.sub.4烷基、CF.sub.3、NO.sub.2或卤素，或R.sub.1和R.sub.2共同形成一个亚甲二氧基基团；每个R.sub.5和R.sub.6，可能相同或不同，为H或C.sub.1-C.sub.4烷基；Z为（CH.sub.2）.sub.n、（CH.sub.2）.sub.n O（CH.sub.2）.sub.n、（CH.sub.2）.sub.n N（R.sub.7）（CH.sub.2）.sub.n、（CH.sub.2）.sub.n N（R.sub.7）（CH.sub.2）.sub.m N（R.sub.7）（CH.sub.2）.sub.n或（CH.sub.2）.sub.n N（CH.sub.2CH.sub.2）.sub.2N（CH.sub.2）.sub.n，其中R.sub.7为H或C.sub.1-C.sub.4烷基，n和m可能相同或不同，均为1至4的整数；或其药学上可接受的酸加盐或N-氧化物；具有抗肿瘤和抗菌活性。
• BIS(ACRIDINECARBOXAMIDE) AND BIS(PHENAZINECARBOXAMIDE) AS ANTITUMOUR AGENTS
  申请人：XENOVA LIMITED

  公开号：EP0934278B1

  公开（公告）日：2002-09-04
• US6114332A
  申请人：——

  公开号：US6114332A

  公开（公告）日：2000-09-05
• 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.