Ethyl (3R)-3-(3,5-dichloro-2-hydroxyphenyl)-3-[(N-{3-hydroxy-5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2yl)amino]benzoyl}glycyl)amino]-propanoate | 726190-58-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: Ethyl (3R)-3-(3,5-dichloro-2-hydroxyphenyl)-3-[(N-{3-hydroxy-5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2yl)amino]benzoyl}glycyl)amino]-propanoate
• 英文别名: ethyl (3R)-3-(3,5-dichloro-2-hydroxyphenyl)-3-[[2-[[3-hydroxy-5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]benzoyl]amino]acetyl]amino]propanoate
• CAS: 726190-58-5
• 化学式: C₂₄H₂₇Cl₂N₅O₇
• 分子量: 568.414
• InChiKey: WEIQWITYVAXMQS-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  182
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Ethyl (3R)-3-(3,5-dichloro-2-hydroxyphenyl)-3-[(N-{3-hydroxy-5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2yl)amino]benzoyl}glycyl)amino]-propanoate 在 sodium hydroxide 作用下， 反应 2.5h， 生成 (3R)-3-(3,5-dichloro-2-hydroxyphenyl)-3-[(N-{3-hydroxy-5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidinyl)amino]benzoyl}glycyl)amino]propanoic acid
  参考文献：
  名称：

  R-Isomers of Arg-Gly-Asp (RGD) mimics as potent αvβ3 inhibitors

  摘要：

  The integrin alpha(v)beta(3), vitronectin receptor, is expressed in a number of cell types and has been shown to mediate adhesion of osteoclasts to bone matrix, vascular smooth muscle cell migration, and angiogenesis. We recently disclosed the discovery of a tripeptide Arg-Gly-Asp (RGD) mimic, which has been shown to be a potent inhibitor of the integrin alpha(v)beta(3) and has excellent anti-angiogenic properties including its suppression of tumor growth in animal models. In other investigations involving RGD mimics, only compounds containing the S-isomers of the beta-amino acids have been shown to be potent. We were surprised to find the potencies of analogs containing enantiomerically pure S-isomers of beta-amino acids which were only marginally better than the corresponding racemic mixtures. We therefore synthesized RGD mimics containing R-isomers of beta-amino acids and found them to be relatively potent inhibitors of alpha(v)beta(3). One of the compounds was examined in tumor models in mice and has been shown to significantly reduce the rate of growth and the size of tumors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.034
• 作为产物：
  描述：

  3-氨基-5-羟基苯甲酸 在 N-甲基吗啉 、 sodium methylate 、 氯甲酸异丁酯 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 7.25h， 生成 Ethyl (3R)-3-(3,5-dichloro-2-hydroxyphenyl)-3-[(N-{3-hydroxy-5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2yl)amino]benzoyl}glycyl)amino]-propanoate
  参考文献：
  名称：

  R-Isomers of Arg-Gly-Asp (RGD) mimics as potent αvβ3 inhibitors

  摘要：

  The integrin alpha(v)beta(3), vitronectin receptor, is expressed in a number of cell types and has been shown to mediate adhesion of osteoclasts to bone matrix, vascular smooth muscle cell migration, and angiogenesis. We recently disclosed the discovery of a tripeptide Arg-Gly-Asp (RGD) mimic, which has been shown to be a potent inhibitor of the integrin alpha(v)beta(3) and has excellent anti-angiogenic properties including its suppression of tumor growth in animal models. In other investigations involving RGD mimics, only compounds containing the S-isomers of the beta-amino acids have been shown to be potent. We were surprised to find the potencies of analogs containing enantiomerically pure S-isomers of beta-amino acids which were only marginally better than the corresponding racemic mixtures. We therefore synthesized RGD mimics containing R-isomers of beta-amino acids and found them to be relatively potent inhibitors of alpha(v)beta(3). One of the compounds was examined in tumor models in mice and has been shown to significantly reduce the rate of growth and the size of tumors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.034

文献信息

• R-isomer of beta amino acid compounds as integrin receptor antagonists derivatives
  申请人：Rogers Thomas

  公开号：US20050020505A1

  公开（公告）日：2005-01-27

  The present invention relates to a class of compounds represented by the Formula I or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising compounds of the Formula I, and methods of selectively inhibiting or antagonizing the α v β 3 and/or the α v β 5 integrin without significantly inhibiting the α v β 6 integrin.

  本发明涉及一类由公式I表示的化合物或其药学上可接受的盐，包括公式I化合物的制药组合物，以及选择性抑制或拮抗αvβ3和/或αvβ5整合素而不显著抑制αvβ6整合素的方法。