1-[4-(((3,5-dimethylanilino)carbonyl)methyl)phenoxy]cyclopentanecarbonyl-L-serine

• 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: 1-[4-(((3,5-dimethylanilino)carbonyl)methyl)phenoxy]cyclopentanecarbonyl-L-serine
• 英文别名: (2S)-2-[[1-[4-[2-(3,5-dimethylanilino)-2-oxoethyl]phenoxy]cyclopentanecarbonyl]amino]-3-hydroxypropanoic acid
• 化学式: C₂₅H₃₀N₂O₆
• 分子量: 454.523
• InChiKey: BNUHSSUEEVUJRX-NRFANRHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  环戊酸 在 N-甲基吗啉 、 氢氧化钾 、 lithium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 硫酸 、 potassium carbonate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 potassium iodide 作用下， 以 四氯化碳 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 110.0h， 生成 1-[4-(((3,5-dimethylanilino)carbonyl)methyl)phenoxy]cyclopentanecarbonyl-L-serine
  参考文献：
  名称：

  Synthesis and X-ray Studies of Chiral Allosteric Modifiers of Hemoglobin

  摘要：

  This study was designed to investigate the effect of chirality on the allosteric activity of a series of Hb allosteric modifiers. The chiral analogues were based on the lead compound (4), JP7, {1-[4-(((3,5-dimethylanilino)carbonyl)methyl)phenoxy]cyclopentanecarboxylic acid} with different D- and L-amino acids conjugated to the JP7 acid moiety. The D-isomers were the most potent in vitro effectors in Hb solutions as well as with whole blood. In general, this study demonstrated that the chirality of extended amino acid side chains in JP7 conjugates plays an important role in observed degree of allosteric activity. The binding site interactions for four analogues were determined by single crystallographic diffraction studies. Conclusions show that the chiral configuration of some of the D-isomers enable the effectors to bind with a greater number of interactions with the protein residues. D- and L-isomers with equivalent or near equivalent allosteric activity did not show any significant differences or interactions between their amino acid side chains and the protein. The most potent effectors, in vitro, were compounds 15 and 19, D-isomers of leucine and phenylalanine, respectively. Compounds 21, 22, 30, and 32 were more potent in vitro in Hb solutions than JP7.

  DOI：

  10.1021/jm010358l

文献信息

• Substituted chiral allosteric hemoglobin modifiers
  申请人：Abraham J. Donald

  公开号：US20050154062A1

  公开（公告）日：2005-07-14

  A family of substituted chiral allosteric effectors of hemoglobin is useful for delivering more oxygen to hypoxic and ischemic tissues by reducing the oxygen affinity of hemoglobin in whole blood.

  一种替代手性变构血红蛋白效应物家族，通过降低全血中血红蛋白的氧亲和力，有助于向低氧和缺血组织输送更多氧气。
• US6486342B1
  申请人：——

  公开号：US6486342B1

  公开（公告）日：2002-11-26
• US6894185B2
  申请人：——

  公开号：US6894185B2

  公开（公告）日：2005-05-17
• Synthesis and X-ray Studies of Chiral Allosteric Modifiers of Hemoglobin
  作者：Amal Mamdouh Youssef、Martin K. Safo、Richmond Danso-Danquah、Gajanan S. Joshi、Jean Kister、Michael C. Marden、Donald J. Abraham

  DOI：10.1021/jm010358l

  日期：2002.3.1

  This study was designed to investigate the effect of chirality on the allosteric activity of a series of Hb allosteric modifiers. The chiral analogues were based on the lead compound (4), JP7, 1-[4-(((3,5-dimethylanilino)carbonyl)methyl)phenoxy]cyclopentanecarboxylic acid} with different D- and L-amino acids conjugated to the JP7 acid moiety. The D-isomers were the most potent in vitro effectors in Hb solutions as well as with whole blood. In general, this study demonstrated that the chirality of extended amino acid side chains in JP7 conjugates plays an important role in observed degree of allosteric activity. The binding site interactions for four analogues were determined by single crystallographic diffraction studies. Conclusions show that the chiral configuration of some of the D-isomers enable the effectors to bind with a greater number of interactions with the protein residues. D- and L-isomers with equivalent or near equivalent allosteric activity did not show any significant differences or interactions between their amino acid side chains and the protein. The most potent effectors, in vitro, were compounds 15 and 19, D-isomers of leucine and phenylalanine, respectively. Compounds 21, 22, 30, and 32 were more potent in vitro in Hb solutions than JP7.