10-[3-[[(3α,5β,7α,12α)-24-(1,1-dimethylethoxy)-7,12-dihydroxy-24-oxocholan-3-yl]oxy]-2-hydroxypropyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tris(1,1-dimethylethyl) ester | 174267-82-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 10-[3-[[(3α,5β,7α,12α)-24-(1,1-dimethylethoxy)-7,12-dihydroxy-24-oxocholan-3-yl]oxy]-2-hydroxypropyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tris(1,1-dimethylethyl) ester
• 英文别名: tert-butyl (4R)-4-[(3R,5R,7R,8R,9S,10S,12S,13R,14S,17R)-7,12-dihydroxy-3-[2-hydroxy-3-[4,7,10-tris[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]propoxy]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 174267-82-4
• 化学式: C₅₇H₁₀₂N₄O₁₂
• 分子量: 1035.46
• InChiKey: FTLRZORESIKFKY-SMVGRRILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  73
• 可旋转键数：
  23
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  188
• 氢给体数：
  3
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  10-[3-[[(3α,5β,7α,12α)-24-(1,1-dimethylethoxy)-7,12-dihydroxy-24-oxocholan-3-yl]oxy]-2-hydroxypropyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tris(1,1-dimethylethyl) ester 在 硫酸 作用下， 反应 2.5h， 以61%的产率得到10-[3-[[(3α,5β,7α,12α)-23-carboxy-7,12-dihydroxy-24-norcholan-3-yl]oxy]-2-hydroxypropyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid
  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：

  tert-butyl cholate 在 sodium hydroxide 、 四丁基硫酸氢铵 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 27.0h， 生成 10-[3-[[(3α,5β,7α,12α)-24-(1,1-dimethylethoxy)-7,12-dihydroxy-24-oxocholan-3-yl]oxy]-2-hydroxypropyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tris(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