dimethyl 3-amino-3',4-oxydibenzoate | 227275-21-0

• 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: dimethyl 3-amino-3',4-oxydibenzoate
• 英文别名: Methyl 3-amino-4-[3-(methoxycarbonyl)phenoxy]benzoate；methyl 3-amino-4-(3-methoxycarbonylphenoxy)benzoate
• CAS: 227275-21-0
• 化学式: C₁₆H₁₅NO₅
• 分子量: 301.299
• InChiKey: AXLCHWMCIGMQCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  87.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl 3-amino-3',4-oxydibenzoate 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， 生成 3-[2-(4-Amino-phenyl)-acetylamino]-4-(3-methoxycarbonyl-phenoxy)-benzoic acid methyl ester
  参考文献：
  名称：

  Studies on selectin blocker. 9. SARs of non-sugar selectin blocker against E-, P-, L-selectin bindings

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(01)00023-2
• 作为产物：
  描述：

  3-羟基苯甲酸甲酯 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 7.0h， 生成 dimethyl 3-amino-3',4-oxydibenzoate
  参考文献：
  名称：

  Studies on selectin blocker. 9. SARs of non-sugar selectin blocker against E-, P-, L-selectin bindings

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(01)00023-2

文献信息

• 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.
• 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.