4-(benzyloxy)-3-methoxy-N-(2,3,4,5-tetramethoxyphenyl)anthranilic acid | 135082-42-7

• 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: 4-(benzyloxy)-3-methoxy-N-(2,3,4,5-tetramethoxyphenyl)anthranilic acid
• 英文别名: 3-Methoxy-4-phenylmethoxy-2-(2,3,4,5-tetramethoxyanilino)benzoic acid
• CAS: 135082-42-7
• 化学式: C₂₅H₂₇NO₈
• 分子量: 469.491
• InChiKey: NZEBEWSFIBGQKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-(benzyloxy)-3-methoxy-N-(2,3,4,5-tetramethoxyphenyl)anthranilic acid 在 哌啶 、 吡啶 、 氯化亚砜 、 sodium hydride 、 三乙胺 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 23.0h， 生成 6-(benzyloxy)-10-<2-(diethylamino)ethyl>-1,2,3,4,5-pentamethoxyacridin-9-one
  参考文献：
  名称：

  Synthesis of the acridone alkaloids, glyfoline and congeners. Structure-activity relationship studies of cytotoxic acridones

  摘要：

  Glyfoline (4, 1,6-dihydroxY-10-methyl-2,3,4,5-tetramethoxyacridin-9-one) and its congeners were synthesized for evaluation of their cytotoxicity. A detailed structure-activity relationships (SAR) of these acridone derivatives were also studied. To study the SAR of glyfoline analogues, substituent(s) at C-1 and C-6 and at the heterocyclic nitrogen of glyfoline nucleus were modified. Nitro- and amino-substituted glyfoline analogues were also synthesized to study the effects of substituent(s) (electron-withdrawing vs electron-donating) on their cytotoxicity. These compounds were synthesized via the Ullmann condensation of anthranilic acids with iodobenzenes or 2-chlorobenzoic acids with aniline-derivatives. The SAR studies showed that 1-hydroxy 9-acridones were more active than their 1-OMe derivatives against cell growth of human leukemic HL-60 cells in culture. Replacement of NMe of glyfoline with NH or N(CH2)2NEt2 resulted in either total loss or dramatic reduction of cytotoxity. Glyfoline congeners with nitro function at the A-ring were inactive, while compounds with amino substituent were shown to be cytotoxic in vitro.

  DOI：

  10.1021/jm00092a022
• 作为产物：
  描述：

  4-(苄氧基)-3-甲氧基-2-硝基苯甲酸 在 sodium dithionite 、 铜 、 potassium carbonate 、 copper(II) oxide 作用下， 以 二乙二醇二甲醚 为溶剂， 反应 4.0h， 生成 4-(benzyloxy)-3-methoxy-N-(2,3,4,5-tetramethoxyphenyl)anthranilic acid
  参考文献：
  名称：

  甘氨酸的合成，甘氨酸是枸杞子的成分（Willd。）Lindl。和潜在的抗癌药

  摘要：

  4-苄氧基-3- methoxyanthranilic酸（缩合3）与5-碘-1,2,3,4-四甲氧基苯（4），得到6-苄氧基1,2,3,4,5-五甲氧基-9-吖啶酮（5），其随后通过N-甲基化，选择性脱-O-甲基化和脱苄基作用转化为乙二醛（1）。合成的草甘膦（1）与从植物中分离出的真实样品完全相同。

  DOI：

  10.1016/s0040-4039(00)74267-5

文献信息

• Synthesis of glyfoline, a constituent of glycosmis citrifolia (Willd.) Lindl. and a potential anticancer agent
  作者：Tsann-Long Su、Krzysztof Dziewiszek、Tian-Shung Wu

  DOI：10.1016/s0040-4039(00)74267-5

  日期：1991.3

  Condensation of 4-benzyloxy-3-methoxyanthranilic acid (3) with 5-iodo-1,2,3,4-tetramethoxybenzene (4) gave 6-benzyloxy-1,2,3,4,5-pentamethoxy-9-acridone (5), which was then converted into glyfoline (1) via N-methylation, selective de-O-methylation, and debenzylation. The synthetic glyfoline (1) is identical with an authentic sample isolated from plant.

  4-苄氧基-3- methoxyanthranilic酸（缩合3）与5-碘-1,2,3,4-四甲氧基苯（4），得到6-苄氧基1,2,3,4,5-五甲氧基-9-吖啶酮（5），其随后通过N-甲基化，选择性脱-O-甲基化和脱苄基作用转化为乙二醛（1）。合成的草甘膦（1）与从植物中分离出的真实样品完全相同。
• US5296602A
  申请人：——

  公开号：US5296602A

  公开（公告）日：1994-03-22
• [EN] MULTISUBSTITUTED 1-HYDROXY-9-ACRIDONES WITH ANTICANCER ACTIVITY
  申请人：——

  公开号：WO1992016509A1

  公开（公告）日：1992-10-01

  [FR] Un composé a la structure (I), dans laquelle R2 et R3 sont identiques ou différents et désignent hydrogène, un groupe alkyle saturé ou insaturé ayant 1 à 5 atomes de carbone, un groupe hydroxyle, un groupe alkyloxyle saturé ou insaturé ayant 1 à 5 atomes de carbone, un groupe O-alkyloxyalkyle dans lequel les alkyles sont identiques ou différents et ont 1 à 5 atomes de carbone, un groupe O-aryloxyalkyle dans lequel l'alkyle a 1 à 5 atomes de carbone, un groupe O-acyle, un groupe O-aroyle ou un groupe O-aryle; R4 désigne hydrogène, un groupe alkyle saturé ou insaturé ayant 1 à 5 atomes de carbone, un groupe hydroxyle, un groupe hydroxyméthyle, un groupe alkyloxyle saturé ou insaturé ayant 1 à 5 atomes de carbone, un groupe O-alkyloxyalkyle dans lequel les alkyles sont identiques ou différents et ont 1 à 5 atomes de carbone, un groupe O-aryloxyalkyle dans lequel l'alkyl a 1 à 5 atomes de carbone, un groupe O-alkyloxyalkyloxyalkyle dans lequel les alkyles sont identiques ou différents et ont 1 à 5 atomes de carbone, un groupe O-acyle, un groupe O-aroyle, un groupe O-aryle; R5, R6 et R7 sont identiques ou différents et désignent hydrogène, un groupe alkyle saturé ou insaturé ayant 1 à 5 atomes de carbone, sulfate, phosphate, un groupe hydroxyle, un groupe alkyloxyle saturé ou insaturé ayant 1 à 5 atomes de carbone, un groupe alkyloxyalkyle dans lequel les alkyles sont identiques ou différents et ont 1 à 5 atomes de carbone, un groupe O-aryloxyalkyle dans lequel l'alkyle a 1 à 5 atomes de carbone, un groupe O-acyle, un groupe O-aroyle, un groupe O-aryle, un groupe nitro, un groupe amino, un groupe N-alkylamino ayant 1 à 5 atomes de carbone, un groupe N,N-dialkylamino dans lequel les alkyles ont 1 à 5 atomes de carbone, un groupe aminoalkyloxyle ayant 1 à 5 atomes de carbone, un groupe N-alkyl-aminoalkyloxyle dans lequel les alkyles sont identiques ou différents et ont 1 à 5 atomes de carbone, un groupe N,N-dialkyl-aminoalkyloxyle dans lequel les alkyles sont identiques ou différents et ont 1 à 5 atomes de carbone,un
  [EN] The present invention provides a compound having structure (I) wherein R?2 and R?3 are the same or different and are hydrogen, a saturated or unsaturated alkyl group having 1 to 5 carbon atoms, a hydroxy group, a saturated or unsaturated alkyloxy group having 1 to 5 carbon atoms, an O-alkyloxyalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an O-aryloxyalkyl group with the alkyl having 1 to 5 carbon atoms, an O-acyl group, an O-aroyl group, or an O-aryl group; R?4 is hydrogen, a saturated or unsaturated alkyl group having 1 to 5 carbon atoms, a hydroxy group, a hydroxymethyl group, a saturated or unsaturated alkyloxy group having 1 to 5 carbon atoms, an O-alkyloxyalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an O-aryloxyalkyl group with the alkyl having 1 to 5 carbon atoms, an O-alkyloxyalkyloxyalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an O-acyl group, an O-aroyl group, or an O-aryl group; R?5, R?6, and R?7 are the same or different and are hydrogen, a saturated or unsaturated alkyl group having 1 to 5 carbon atoms, sulfate, phosphate, a hydroxy group, a saturated or unsaturated alkyloxy group having 1 to 5 carbon atoms, an O-alkyloxyalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an O-aryloxyalkyl group with the alkyl having 1 to 5 carbon atoms, an O-acyl group, an O-aroyl group, an O-aryl group, a nitro group, an amino group, an N-alkylamino group having 1 to 5 carbon atoms, an N,N-dialkylamino group with each alkyl having 1 to 5 carbon atoms, an aminoalkyloxy group having 1 to 5 carbon atoms, an N-alkyl-aminoalkyloxy group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an N,N-dialkyl-aminoalkyloxy group wherein each alkyl is the same or different having 1 to 5 carbon atoms, a quaternary ammonium alkyloxy salt, or a halogen; and R?10 is hydrogen, a saturated or unsaturated alkyl group having 1 to 5 carbon atoms, an aminoalkyl group having 1 to 5 carbon atoms, an N-alkylaminoalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, an N,N-dialkylaminoalkyl group wherein each alkyl is the same or different having 1 to 5 carbon atoms, or an amino acid moiety. The present invention also provides a method for synthesizing a compound having the above-identified structure as well as the intermediate compounds produced according to that method. The present invention further provides a pharmaceutical composition comprising the above compounds. Lastly, the present invention provides a method of inhibiting growth of tumor cells.
• Synthesis of the acridone alkaloids, glyfoline and congeners. Structure-activity relationship studies of cytotoxic acridones
  作者：Tsann Long Su、Bernd Kohler、Ting Chao Chou、Moon Woo Chun、Kyoichi A. Watanabe

  DOI：10.1021/jm00092a022

  日期：1992.7

  Glyfoline (4, 1,6-dihydroxY-10-methyl-2,3,4,5-tetramethoxyacridin-9-one) and its congeners were synthesized for evaluation of their cytotoxicity. A detailed structure-activity relationships (SAR) of these acridone derivatives were also studied. To study the SAR of glyfoline analogues, substituent(s) at C-1 and C-6 and at the heterocyclic nitrogen of glyfoline nucleus were modified. Nitro- and amino-substituted glyfoline analogues were also synthesized to study the effects of substituent(s) (electron-withdrawing vs electron-donating) on their cytotoxicity. These compounds were synthesized via the Ullmann condensation of anthranilic acids with iodobenzenes or 2-chlorobenzoic acids with aniline-derivatives. The SAR studies showed that 1-hydroxy 9-acridones were more active than their 1-OMe derivatives against cell growth of human leukemic HL-60 cells in culture. Replacement of NMe of glyfoline with NH or N(CH2)2NEt2 resulted in either total loss or dramatic reduction of cytotoxity. Glyfoline congeners with nitro function at the A-ring were inactive, while compounds with amino substituent were shown to be cytotoxic in vitro.