4-[3,5-双(甲氧基羰基)苯氧基]-3-氨基苯甲酸甲酯 | 100596-38-1

• 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: 4-[3,5-双(甲氧基羰基)苯氧基]-3-氨基苯甲酸甲酯
• 英文名称: dimethyl 5-[3-amino-4-methoxycarbonylphenoxy]isophthalate
• 英文别名: dimethyl 5-(2-amino-4-(methoxycarbonyl)phenoxy) isophthalate；dimethyl 5-(2-amino-4-(methoxycarbonyl)phenoxy)isophthalate；1,3-Benzenedicarboxylic acid, 5-(2-amino-4-(methoxycarbonyl)phenoxy)-, dimethyl ester；dimethyl 5-(2-amino-4-methoxycarbonylphenoxy)benzene-1,3-dicarboxylate
• CAS: 100596-38-1
• 化学式: C₁₈H₁₇NO₇
• 分子量: 359.335
• InChiKey: XPNBOEYBQIADSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  8

安全信息

• 海关编码：
  2922509090

反应信息

• 作为反应物：
  描述：

  4-[3,5-双(甲氧基羰基)苯氧基]-3-氨基苯甲酸甲酯 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 为溶剂， 反应 43.0h， 生成 dimethyl 5-[4-methoxycarbonyl-2-(4-octadecanoylaminobenzoylamino)phenoxy]isophthalate
  参考文献：
  名称：

  Study on Selectin Blocker. 8. Lead Discovery of a Non-Sugar Antagonist Using a 3D-Pharmacophore Model

  摘要：

  We have developed a pharmacophore model of a ligand/E-selectin complex to screen drug candidates for selectin blockers. In a series of sugar mimetic studies of the E-selectin ligand, sialyl Lewis X (sLe(x)), we have already found a potent compound, a sulfated Le(x) analogue (1), and also have proposed how compound 1 binds to E-selectin (Tsujishita, H.; Hiramatsu, Y.; Kondo, N.; Ohmoto, H.; Kondo, H.; Kiso, M.; Hasegawa, A. J. Med. Chem. 1997, 40, 362-369). To find drug candidates that fit into the binding pocket of E-selectin, we constructed an original 3D-pharmacophore model from structural information of a compound 1/E-selectin complex model and screened lead compounds for selectin blockers using a commercially available database ACD-3D. As a result, we discovered a lead compound (2) containing good selectin inhibitory activity, and in addition, we succeeded to preliminarily optimize it to a more active lead compound (3) with micromolar IC50 values, based on the 3D-pharmacophore model investigation. This methodology using the 3D-pharmacophore model could be applicable as a pre-screen system for selectin blockers.

  DOI：

  10.1021/jm990342j
• 作为产物：
  描述：

  5-羟基间苯二甲酸二甲酯 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、303.98 kPa 条件下， 反应 6.0h， 生成 4-[3,5-双(甲氧基羰基)苯氧基]-3-氨基苯甲酸甲酯
  参考文献：
  名称：

  Study on Selectin Blocker. 8. Lead Discovery of a Non-Sugar Antagonist Using a 3D-Pharmacophore Model

  摘要：

  We have developed a pharmacophore model of a ligand/E-selectin complex to screen drug candidates for selectin blockers. In a series of sugar mimetic studies of the E-selectin ligand, sialyl Lewis X (sLe(x)), we have already found a potent compound, a sulfated Le(x) analogue (1), and also have proposed how compound 1 binds to E-selectin (Tsujishita, H.; Hiramatsu, Y.; Kondo, N.; Ohmoto, H.; Kondo, H.; Kiso, M.; Hasegawa, A. J. Med. Chem. 1997, 40, 362-369). To find drug candidates that fit into the binding pocket of E-selectin, we constructed an original 3D-pharmacophore model from structural information of a compound 1/E-selectin complex model and screened lead compounds for selectin blockers using a commercially available database ACD-3D. As a result, we discovered a lead compound (2) containing good selectin inhibitory activity, and in addition, we succeeded to preliminarily optimize it to a more active lead compound (3) with micromolar IC50 values, based on the 3D-pharmacophore model investigation. This methodology using the 3D-pharmacophore model could be applicable as a pre-screen system for selectin blockers.

  DOI：

  10.1021/jm990342j

文献信息

• Heparanase inhibitors and uses thereof
  申请人：Van Gelder M. Joel

  公开号：US20070185176A1

  公开（公告）日：2007-08-09

  The invention provides heparanase inhibitors suitable for treatment of diseases and disorders caused by or associated with heparanase catalytic activity such as cancer, inflammatory disorders and autoimmune diseases.

  该发明提供了适用于治疗由或与肝素酶催化活性相关的疾病和疾病的肝素酶抑制剂，例如癌症，炎症性疾病和自身免疫疾病。
• Studies on selectin blocker. 9. SARs of non-sugar selectin blocker against E-, P-, L-selectin bindings
  作者：Hideki Moriyama、Yasuyuki Hiramatsu、Takao Kiyoi、Toshio Achiha、Yoshimasa Inoue、Hirosato Kondo

  DOI：10.1016/s0968-0896(01)00023-2

  日期：2001.6

  As a part of study of selectin blockers, we have already reported that a non-sugar selectin antagonist (3) was successfully discovered using a computational screening (Hiramatsu, Y.; Tsukida, T.; Nakai, Y.; Inoue, Y.; Kondo, H. J. Med. Chem. 2000, 43 1476). To investigate the SARs of compound 3 against E-, P-, and L-selectins, we synthesized the derivatives of compound 3 and evaluated their inhibitory activities toward selectin bindings. The structural diversity of compound 3 contained the following. (1) a modification of the spacer unit (4-7), (2) a modification of the tail unit (8-11), (3) a modification of the head unit (12-18). As a result, it was found that a non-sugar based selectin blocker (3) could be a potential lead compound for E-, P-, and L-selectin blockers and some of the derivatives showed broad and/or selective inhibitory activities toward the E-, P-, and L-selectins. In addition, it was found that the experimental evidence well supported that the computational screening using 3D-pharmacophore model could be useful methodology to find out a new lead for the several type of selectin blockers, which included a broad and/or a selective inhibitor. (C) 2001 Published by Elsevier Science Ltd.
• HEPARANASE INHIBITORS AND USES THEREOF
  申请人：Insight Biopharmaceuticals Ltd

  公开号：EP1720828A2

  公开（公告）日：2006-11-15
• [EN] HEPARANASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'HEPARANASE ET UTILISATIONS
  申请人：INSIGHT BIOPHARMACEUTICALS LTD

  公开号：WO2005074375A2

  公开（公告）日：2005-08-18

  The invention provides heparanase inhibitors suitable for treatment of diseases and disorders caused by or associated with heparanase catalytic activity such as cancer, inflammatory disorders and autoimmune diseases.
• Study on Selectin Blocker. 8. Lead Discovery of a Non-Sugar Antagonist Using a 3D-Pharmacophore Model
  作者：Yasuyuki Hiramatsu、Takahiro Tsukida、Yoshiyuki Nakai、Yoshimasa Inoue、Hirosato Kondo

  DOI：10.1021/jm990342j

  日期：2000.4.1

  We have developed a pharmacophore model of a ligand/E-selectin complex to screen drug candidates for selectin blockers. In a series of sugar mimetic studies of the E-selectin ligand, sialyl Lewis X (sLe(x)), we have already found a potent compound, a sulfated Le(x) analogue (1), and also have proposed how compound 1 binds to E-selectin (Tsujishita, H.; Hiramatsu, Y.; Kondo, N.; Ohmoto, H.; Kondo, H.; Kiso, M.; Hasegawa, A. J. Med. Chem. 1997, 40, 362-369). To find drug candidates that fit into the binding pocket of E-selectin, we constructed an original 3D-pharmacophore model from structural information of a compound 1/E-selectin complex model and screened lead compounds for selectin blockers using a commercially available database ACD-3D. As a result, we discovered a lead compound (2) containing good selectin inhibitory activity, and in addition, we succeeded to preliminarily optimize it to a more active lead compound (3) with micromolar IC50 values, based on the 3D-pharmacophore model investigation. This methodology using the 3D-pharmacophore model could be applicable as a pre-screen system for selectin blockers.