N-[芴甲氧羰基]-N-甲基-S-(三苯基甲基)-L-高半胱氨酸 | 526210-71-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: N-[芴甲氧羰基]-N-甲基-S-(三苯基甲基)-L-高半胱氨酸
• 英文名称: N-(9-fluorenylmethoxycarbonyl)-N-methyl-S-trityl-L-homocysteine
• 英文别名: N-(9H-Fluorene-9-ylmethyloxycarbonyl)-N-methyl-S-trityl-L-homocysteine；(S)-2-(N-Fmoc-N-methyl-amino)-4-tritylsulfanyl-butyric acid；(2S)-2-[9H-fluoren-9-ylmethoxycarbonyl(methyl)amino]-4-tritylsulfanylbutanoic acid
• CAS: 526210-71-9
• 化学式: C₃₉H₃₅NO₄S
• 分子量: 613.777
• InChiKey: XVDJDZSADBCCPL-BHVANESWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  92.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-[芴甲氧羰基]-N-甲基-S-(三苯基甲基)-L-高半胱氨酸 、 Fmoc-O-叔丁基-L-酪氨酸 、 N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-L-赖氨酸 、 N-alpha-芴甲氧羰基-N-in-叔丁氧羰基-D-色氨酸 、 alkaline earth salt of/the/ methylsulfuric acid 生成 L-phenylalanyl-N-methyl-S-trityl-L-homocysteinyl-O-tert-butyl-L-tyrosinyl-Nⁱⁿ-tert-butoxycarbonyl-D-tryptophanyl-N-ε-tert-butoxycarbonyl-L-lysinyl-O-tert-butyl-L-threonine
  参考文献：
  名称：

  Somatostatin Receptor-Binding Peptides Suitable for Tumor Radiotherapy with Re-188 or Re-186. Chemistry and Initial Biological Studies

  摘要：

  Somatostatin derivative peptides previously designed for radiodiagnostic purposes (Tc-99m P829 or Tc-99m depreotide) were reoptimized for radiotherapy of tumors with rhenium radioisotopes. An optimized pharmacophore peptide P1839 was derived by in vitro binding affinity assay to AR42J rat pancreatic tumor cell membranes. Peptides with chelating domains and their oxorhenium(V) complexes were tested in vitro for binding to NCI H69 human SCLC tumor membranes. Further optimization entailed radiolabeling with Tc-99m and biodistribution in an AR42J xenograft mouse model. Kidney uptake was decreased substantially by removing positively charged residues. Neutral N3S diamide amine thiol chelators with no adjacent positive charges had the best overall properties. Substituting an aromatic amino acid into the chelator approximately doubled the tumor uptake. The final optimized peptide P2045 (39) radiolabeled with Tc-99m exhibited increased tumor uptake (similar to 25 %ID/g at 1.5 h), lower kidney uptake (similar to 4.8 %ID/g at 1.5 h), and extensive urinary excretion (59 %ID at 1.5 h). Finally, comparison biodistribution studies between Tc-99m and Re-188 (39) showed a good correlation between the two metal complexes and demonstrated prolonged tumor retention (>= 24 h).

  DOI：

  10.1021/jm061290i
• 作为产物：
  描述：

  N-methyl-S-trityl-L-homocysteine 、 9-芴甲基-N-琥珀酰亚胺基碳酸酯 在 sodium carbonate 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 丙酮 为溶剂， 生成 N-[芴甲氧羰基]-N-甲基-S-(三苯基甲基)-L-高半胱氨酸
  参考文献：
  名称：

  N-methyl-homocysteines and their use as well as process for their production

  摘要：

  描述了N-甲基同型半胱氨酸的合成及其用途。

  公开号：

  US20030120032A1

文献信息

• N-METHYL-HOMOCYSTEINE UND IHRE VERWENDUNG SOWIE VERFAHREN ZU IHRER HERSTELLUNG
  申请人：SCHERING AKTIENGESELLSCHAFT

  公开号：EP1444194A1

  公开（公告）日：2004-08-11
• US7659364B2
  申请人：——

  公开号：US7659364B2

  公开（公告）日：2010-02-09
• [DE] N-METHYL-HOMOCYSTEINE UND IHRE VERWENDUNG SOWIE VERFAHREN ZU IHRER HERSTELLUNG<br/>[EN] N-METHYL-HOMOCYSTINES, USE THEREOF AND METHOD FOR THE PRODUCTION THEREOF<br/>[FR] N-METHYLHOMOCYSTEINES, LEUR UTILISATION ET LEUR PROCEDE DE PRODUCTION
  申请人：SCHERING AG

  公开号：WO2003042163A1

  公开（公告）日：2003-05-22

  Es wird die Synthese von N-Methyl-Homocysteinen und ihre Verwendung beschrieben.
• N-methyl-homocysteines and their use as well as process for their production
  申请人：Schering AG

  公开号：US20030120032A1

  公开（公告）日：2003-06-26

  The synthesis of N-methyl-homocysteines and their use are described.

  描述了N-甲基同型半胱氨酸的合成及其用途。
• Somatostatin Receptor-Binding Peptides Suitable for Tumor Radiotherapy with Re-188 or Re-186. Chemistry and Initial Biological Studies
  作者：John E. Cyr、Daniel A. Pearson、David M. Wilson、Carol A. Nelson、Mary Guaraldi、Michael T. Azure、John Lister-James、Ludger M. Dinkelborg、Richard T. Dean

  DOI：10.1021/jm061290i

  日期：2007.3.1

  Somatostatin derivative peptides previously designed for radiodiagnostic purposes (Tc-99m P829 or Tc-99m depreotide) were reoptimized for radiotherapy of tumors with rhenium radioisotopes. An optimized pharmacophore peptide P1839 was derived by in vitro binding affinity assay to AR42J rat pancreatic tumor cell membranes. Peptides with chelating domains and their oxorhenium(V) complexes were tested in vitro for binding to NCI H69 human SCLC tumor membranes. Further optimization entailed radiolabeling with Tc-99m and biodistribution in an AR42J xenograft mouse model. Kidney uptake was decreased substantially by removing positively charged residues. Neutral N3S diamide amine thiol chelators with no adjacent positive charges had the best overall properties. Substituting an aromatic amino acid into the chelator approximately doubled the tumor uptake. The final optimized peptide P2045 (39) radiolabeled with Tc-99m exhibited increased tumor uptake (similar to 25 %ID/g at 1.5 h), lower kidney uptake (similar to 4.8 %ID/g at 1.5 h), and extensive urinary excretion (59 %ID at 1.5 h). Finally, comparison biodistribution studies between Tc-99m and Re-188 (39) showed a good correlation between the two metal complexes and demonstrated prolonged tumor retention (>= 24 h).