N-[2-[(2-aminoethyl)amino]ethyl]-O-[(4-nitrophenyl)methyl]-D,L-serine 1,1-dimethylethyl ester

• 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: N-[2-[(2-aminoethyl)amino]ethyl]-O-[(4-nitrophenyl)methyl]-D,L-serine 1,1-dimethylethyl ester
• 英文别名: N-[2-[(2-aminoethyl)amino]ethyl]-O-(4-nitrophenyl)methyl-D,L-serine t-butyl ester；tert-butyl 2-[2-(2-aminoethylamino)ethylamino]-3-[(4-nitrophenyl)methoxy]propanoate
• 化学式: C₁₈H₃₀N₄O₅
• 分子量: 382.46
• InChiKey: ONKBHIYFVUGESN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  27
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  131
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  溴乙酸叔丁酯 、 N-[2-[(2-aminoethyl)amino]ethyl]-O-[(4-nitrophenyl)methyl]-D,L-serine 1,1-dimethylethyl ester 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以61%的产率得到6,9,12-tris[2-(1,1-dimethylethoxy)-2-oxoethyl]-2,2-dimethyl-5-[[(4-nitrophenyl)methoxy]methyl]-4-oxo-3-oxa-6,9,12-triazatetradecan-14-oic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Conjugates of Gadolinium Complexes to Bile Acids as Hepatocyte-Directed Contrast Agents for Magnetic Resonance Imaging

  摘要：

  A series of structurally different Gd(III) conjugates incorporating a bile acid moiety have been prepared. Polyaminopolycarboxylic ligands such as diethylenetriaminepentaacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA) have been selected as chelating subunit for the Gd(III) ion. Cholic acid, cholylglycine, and cholyltaurine have been incorporated as the bile acid moieties. In first generation conjugates the Gd(III) complex is linked to the carboxyl group of cholic acid. Second generation conjugates feature the attachment of the Gd(III) complex to the 3 position of the steroidic backbone of the bile acid. Finally, in third generation conjugates the Gd(III) complex is attached to the E nitrogen atom of cholyllysine. The conjugates are eliminated through the biliary route to a various extent (7.5 to 77% in rats) according to their structural features. Among the most promising terms, a second generation conjugate in which the Gd(III) complex is linked to cholic acid through the 3alpha hydroxy group seems to enter hepatocytes using the Na+/taurocholate transporter. Noticeably, some of the second generation conjugates are characterized by very high tolerabilities (LD50 up to 9.5 mmol/kg) after intravenous administration in mice.

  DOI：

  10.1021/jm0310683
• 作为产物：
  描述：

  二乙烯三胺 、 2-bromo-3-[(4-nitrophenyl)methoxy]propionic acid 1,1-dimethylethyl ester 在 氯化钠 、 乙醚 、 水 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以to obtain 12 g of the desired product (0.031 mol)的产率得到N-[2-[(2-aminoethyl)amino]ethyl]-O-[(4-nitrophenyl)methyl]-D,L-serine 1,1-dimethylethyl ester
  参考文献：
  名称：

  Paramagnetic metal icon chelates and use thereof as contrast agents in

  摘要：

  本发明描述了新型顺磁性金属离子螯合物及其作为“磁共振成像”（M.R.I.）诊断技术中胃肠道和特别是肝脏的对比剂的使用。这些新型化合物是由胆酸与螯合剂结合而成，能够螯合二价和三价金属离子。该化合物的化学式为A-L-B，其中A是胆酸及其衍生物的残基，B是具有原子序数20到31、39、42、43、44、49、57到83的二价或三价金属离子的螯合剂残基，L是连接A和B之间的配体。

  公开号：

  US05649537A1

文献信息

• Paramagnetic metal icon chelates and use thereof as contrast agents in
  申请人：Dibra S.p.A.

  公开号：US05649537A1

  公开（公告）日：1997-07-22

  Novel paramagnetic metal ion chelates and their use as contrast agents in the diagnostic technique known as "magnetic resonance imaging" (M.R.I.) of the gastrointestinal tract and particularly of the liver, are described. The novel compounds result from the conjugation of a bile acid with a chelating agent and are capable of chelating the ions of bivalent and trivalent metals. The compounds have formula A-L-B in which A is the residue of a bile acid and derivatives of a bile acid, B is the residue of a chelating agent of a bivalent or trivalent metal ion having an atomic number of 20 to 31, 39, 42, 43, 44, 49, 57 to 83, L is a ligand between A and B.

  本发明描述了新型顺磁性金属离子螯合物及其作为“磁共振成像”（M.R.I.）诊断技术中胃肠道和特别是肝脏的对比剂的使用。这些新型化合物是由胆酸与螯合剂结合而成，能够螯合二价和三价金属离子。该化合物的化学式为A-L-B，其中A是胆酸及其衍生物的残基，B是具有原子序数20到31、39、42、43、44、49、57到83的二价或三价金属离子的螯合剂残基，L是连接A和B之间的配体。
• US5649537A
  申请人：——

  公开号：US5649537A

  公开（公告）日：1997-07-22
• Conjugates of Gadolinium Complexes to Bile Acids as Hepatocyte-Directed Contrast Agents for Magnetic Resonance Imaging
  作者：Pier Lucio Anelli、Luciano Lattuada、Vito Lorusso、Giovanna Lux、Alberto Morisetti、Pierfrancesco Morosini、Michele Serleti、Fulvio Uggeri

  DOI：10.1021/jm0310683

  日期：2004.7.1

  A series of structurally different Gd(III) conjugates incorporating a bile acid moiety have been prepared. Polyaminopolycarboxylic ligands such as diethylenetriaminepentaacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA) have been selected as chelating subunit for the Gd(III) ion. Cholic acid, cholylglycine, and cholyltaurine have been incorporated as the bile acid moieties. In first generation conjugates the Gd(III) complex is linked to the carboxyl group of cholic acid. Second generation conjugates feature the attachment of the Gd(III) complex to the 3 position of the steroidic backbone of the bile acid. Finally, in third generation conjugates the Gd(III) complex is attached to the E nitrogen atom of cholyllysine. The conjugates are eliminated through the biliary route to a various extent (7.5 to 77% in rats) according to their structural features. Among the most promising terms, a second generation conjugate in which the Gd(III) complex is linked to cholic acid through the 3alpha hydroxy group seems to enter hepatocytes using the Na+/taurocholate transporter. Noticeably, some of the second generation conjugates are characterized by very high tolerabilities (LD50 up to 9.5 mmol/kg) after intravenous administration in mice.