(2S,4R) methyl 1-[(E)-3-(3,4-dimethoxyphenyl)-2-propenoyl]-4-hydroxy-2-pyrrolidinecarboxylate | 769970-64-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,4R) methyl 1-[(E)-3-(3,4-dimethoxyphenyl)-2-propenoyl]-4-hydroxy-2-pyrrolidinecarboxylate
• 英文别名: (2S,4R)-methyl 4-hydroxy-1-((E)-3-(3,4-dimethoxyphenyl)acryloyl)pyrrolidine-2-carboxylate；methyl (2S,4R,E)-4-hydroxy-1-(3-(3,4-dimethoxyphenyl)acryloyl)pyrrolidine-2-carboxylate；methyl (2S,4R)-1-[(E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]-4-hydroxypyrrolidine-2-carboxylate
• CAS: 769970-64-1
• 化学式: C₁₇H₂₁NO₆
• 分子量: 335.357
• InChiKey: WXWCEHFFHYJWIF-JOVKLMRISA-N

物化性质

• 熔点：
  62.5-64.5 °C
• 沸点：
  548.5±50.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  85.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,4R) methyl 1-[(E)-3-(3,4-dimethoxyphenyl)-2-propenoyl]-4-hydroxy-2-pyrrolidinecarboxylate 在 钯 sodium azide 、 氢气 、 三乙胺 、 calcium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0~55.0 ℃ 、101.33 kPa 条件下， 反应 27.0h， 生成 (2S,4S) methyl 1-[(E)-3-(3,4-dimethoxyphenyl)-2-propenoyl]-4-[(E)-3-(4-methoxyphenyl)-2-propenoyl]amide-2-pyrrolidinecarboxylate
  参考文献：
  名称：

  Design, synthesis, and activity of caffeoyl pyrrolidine derivatives as potential gelatinase inhibitors

  摘要：

  The synthesis and biological evaluation of caffonyl pyrrolidine derivatives as MMPs inhibitors are reported in this paper. Inhibiting activities of synthesized compounds on gelatinase (MMP-2 and -9) were tested by using succinylated gelatin as substrate. Structure-activity relationship results from these tested compounds demonstrated that longer and more flexible side chain linked to the pyrrolidine ring at C-4 produced higher activity at gelatinase. Furthermore, aromatic heterocycle and sulfamide in the same position could enhance the activities. Compounds with free phenol hydroxyl group showed higher activity compared to methylated derivatives (or counterparts), which confirms the importance of phenol hydroxyl functionality in the interaction with gelatinase. The anti-metastasis model of mice bearing H-22 tumor cell was used to evaluate their in vivo inhibiting activities. All tested compounds were orally administered at a dose of 50 or 100 mg/kg, 6 days/week for two weeks. The test results demonstrated that most of these inhibitors showed significant anti-cancer activities (inhibitory rate > 35%) and were devoid of toxic effects. Compound 29 showed the highest inhibitory rate at 69.25%, indicating that it might be a promising lead compound. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.025
• 作为产物：
  描述：

  TRANS-咖啡酸 在 sodium hydroxide 、 氯化亚砜 、 三乙胺 作用下， 以 吡啶 、 苯 为溶剂， 反应 12.83h， 生成 (2S,4R) methyl 1-[(E)-3-(3,4-dimethoxyphenyl)-2-propenoyl]-4-hydroxy-2-pyrrolidinecarboxylate
  参考文献：
  名称：

  Design, synthesis, and activity of caffeoyl pyrrolidine derivatives as potential gelatinase inhibitors

  摘要：

  The synthesis and biological evaluation of caffonyl pyrrolidine derivatives as MMPs inhibitors are reported in this paper. Inhibiting activities of synthesized compounds on gelatinase (MMP-2 and -9) were tested by using succinylated gelatin as substrate. Structure-activity relationship results from these tested compounds demonstrated that longer and more flexible side chain linked to the pyrrolidine ring at C-4 produced higher activity at gelatinase. Furthermore, aromatic heterocycle and sulfamide in the same position could enhance the activities. Compounds with free phenol hydroxyl group showed higher activity compared to methylated derivatives (or counterparts), which confirms the importance of phenol hydroxyl functionality in the interaction with gelatinase. The anti-metastasis model of mice bearing H-22 tumor cell was used to evaluate their in vivo inhibiting activities. All tested compounds were orally administered at a dose of 50 or 100 mg/kg, 6 days/week for two weeks. The test results demonstrated that most of these inhibitors showed significant anti-cancer activities (inhibitory rate > 35%) and were devoid of toxic effects. Compound 29 showed the highest inhibitory rate at 69.25%, indicating that it might be a promising lead compound. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.025

文献信息

• Design, synthesis and preliminary evaluation of novel pyrrolidine derivatives as matrix metalloproteinase inhibitors
  作者：Xian-Chao Cheng、Qiang Wang、Hao Fang、Wei Tang、Wen-Fang Xu

  DOI：10.1016/j.ejmech.2007.12.020

  日期：2008.10

  of novel pyrrolidine derivatives were designed, synthesized and assayed for their inhibitory activities on matrix metalloproteinase 2 (MMP-2) and aminopeptidase N (AP-N). The results showed that these pyrrolidine derivatives exhibited highly selective inhibition against MMP-2 as compared with AP-N. The hydroxamates 8a-c were equally or more potent MMP-2 inhibitors than the positive control LY52. The

  设计，合成和测定了一系列新颖的吡咯烷衍生物对基质金属蛋白酶2（MMP-2）和氨基肽酶N（AP-N）的抑制活性。结果表明，与AP-N相比，这些吡咯烷衍生物表现出对MMP-2的高度选择性抑制。异羟肟酸酯8a-c是与阳性对照LY52同等或更有效的MMP-2抑制剂。提出了最有效的化合物8a与MMP-2的结合方式。构效关系也作了简要讨论。
• Design, synthesis and preliminary evaluation of new cinnamoyl pyrrolidine derivatives as potent gelatinase inhibitors
  作者：Li Zhang、Jie Zhang、Hao Fang、Qiang Wang、Wenfang Xu

  DOI：10.1016/j.bmc.2006.09.015

  日期：2006.12

  A series of new cinnamoyl pyrrolidine derivatives have been synthesized based on the L-hydroxyproline scaffold and inhibiting activities on gelatinase (MMP-2 and -9) and APN were tested. Structure-activity relationship studies showed that the side chain with aromatic ring at C4 in pyrrolidine ring showed better inhibitory activities on gelatinase than aliphatic side chain. Most compounds exhibited poor activities on APN compared with MMP-2. Within this series, three compounds, A8, B9 and C10, have the good potency (IC50 = 5.2-9.7 nM) and could be used as lead compounds in the future. (c) 2006 Elsevier Ltd. All rights reserved.
• Design, synthesis, and activity of caffeoyl pyrrolidine derivatives as potential gelatinase inhibitors
  作者：Ya-Lin Li、Wen-Fang Xu

  DOI：10.1016/j.bmc.2004.07.025

  日期：2004.10

  The synthesis and biological evaluation of caffonyl pyrrolidine derivatives as MMPs inhibitors are reported in this paper. Inhibiting activities of synthesized compounds on gelatinase (MMP-2 and -9) were tested by using succinylated gelatin as substrate. Structure-activity relationship results from these tested compounds demonstrated that longer and more flexible side chain linked to the pyrrolidine ring at C-4 produced higher activity at gelatinase. Furthermore, aromatic heterocycle and sulfamide in the same position could enhance the activities. Compounds with free phenol hydroxyl group showed higher activity compared to methylated derivatives (or counterparts), which confirms the importance of phenol hydroxyl functionality in the interaction with gelatinase. The anti-metastasis model of mice bearing H-22 tumor cell was used to evaluate their in vivo inhibiting activities. All tested compounds were orally administered at a dose of 50 or 100 mg/kg, 6 days/week for two weeks. The test results demonstrated that most of these inhibitors showed significant anti-cancer activities (inhibitory rate > 35%) and were devoid of toxic effects. Compound 29 showed the highest inhibitory rate at 69.25%, indicating that it might be a promising lead compound. (C) 2004 Elsevier Ltd. All rights reserved.